acid-phosphatase and Prostatic-Neoplasms

The inactivation of tumor suppressor genes (TSGs) plays a vital role in the progression of human cancers. Nevertheless, those ubiquitous TSGs have been shown with limited roles in various stages of diverse carcinogenesis. Investigation on identifying unique TSG, especially for early stage of carcinogenesis, is imperative. As such, the search for organ-specific TSGs has emerged as a major strategy in cancer research. Prostate cancer (PCa) has the highest incidence in solid tumors in US males. Cellular prostatic acid phosphatase (cPAcP) is a prostate-specific differentiation antigen. Despite intensive studies over the past several decades on PAcP as a PCa biomarker, the role of cPAcP as a PCa-specific tumor suppressor has only recently been emerged and validated. The mechanism underlying the pivotal role of cPAcP as a prostate-specific TSG is, in part, due to its function as a protein tyrosine phosphatase (PTP) as well as a phosphoinositide phosphatase (PIP), an apparent functional homologue to phosphatase and tensin homolog (PTEN) in PCa cells. This review is focused on discussing the function of this authentic prostate-specific tumor suppressor and the mechanism behind the loss of cPAcP expression leading to prostate carcinogenesis. We review other phosphatases' roles as TSGs which regulate oncogenic PI3K signaling in PCa and discuss the functional similarity between cPAcP and PTEN in prostate carcinogenesis.

Topics: Acid Phosphatase; Animals; Carcinogenesis; Epithelium; Genes, Tumor Suppressor; Humans; Male; Prostate; Prostatic Neoplasms; Protein Tyrosine Phosphatases; PTEN Phosphohydrolase; Sequence Homology

Human prostatic acid phosphatase (PAcP) is a 100 kDa glycoprotein composed of two subunits. Recent advances demonstrate that cellular PAcP (cPAcP) functions as a protein tyrosine phosphatase by dephosphorylating ErbB-2/Neu/HER-2 at the phosphotyrosine residues in prostate cancer (PCa) cells, which results in reduced tumorigenicity. Further, the interaction of cPAcP and ErbB-2 regulates androgen sensitivity of PCa cells. Knockdown of cPAcP expression allows androgen-sensitive PCa cells to develop the castration-resistant phenotype, where cells proliferate under an androgen-reduced condition. Thus, cPAcP has a significant influence on PCa cell growth. Interestingly, promoter analysis suggests that PAcP expression can be regulated by NF-κB, via a novel binding sequence in an androgen-independent manner. Further understanding of PAcP function and regulation of expression will have a significant impact on understanding PCa progression and therapy.

Topics: Acid Phosphatase; Amino Acid Sequence; Gene Expression Regulation, Enzymologic; Humans; Male; Models, Genetic; Molecular Sequence Data; Prostatic Neoplasms; Sequence Homology, Amino Acid; Signal Transduction

Prostate cancer (PCa) is a leading cause of cancer-related death of men globally. Since its introduction, there has been intense debate as to the effectiveness of the prostate specific antigen (PSA) test as a screening tool for PCa. It is now evident that the PSA test produces unacceptably high rates of false positive results and is not prognostic. Here we review the current status of molecular biomarkers that promise to be prognostic and that might inform individual patient management. It highlights current efforts to identify biomarkers obtained by minimally invasive methods and discusses current knowledge with regard to gene fusions, mRNA and microRNAs, immunology, and cancer-associated microparticles.

Topics: Acid Phosphatase; Biomarkers, Tumor; Humans; Male; Prostate-Specific Antigen; Prostatic Neoplasms; Protein Tyrosine Phosphatases

Sipuleucel-T, the first autologous cellular immunotherapy approved by the United States Food and Drug Administration, is designed to stimulate an immune response to prostate cancer. Sipuleucel-T is manufactured by culturing a patient's peripheral blood mononuclear cells, including autologous antigen presenting cells (APCs), with a recombinant protein comprising a tumor-associated antigen (prostatic acid phosphatase [PAP]) and granulocyte colony-macrophage stimulating factor (GM-CSF). A full course of treatment comprises 3 infusions of sipuleucel-T, given at approximately 2-week intervals. The pattern of APC activation is consistent with priming by the first infusion, and boosting by the second and third infusions. Preclinical and clinical studies have demonstrated evidence of a robust antigen-specific immune response that includes a progressive and persistent increase in antigen-specific cellular and humoral immune responses. Treatment with sipuleucel-T has demonstrated a survival benefit in Phase 3 studies of subjects with metastatic castrate resistant (hormone refractory) prostate cancer (mCRPC). Adverse events with sipuleucel-T were generally mild to moderate and resolved within 2 days. Serious adverse events, autoimmune events, and cerebrovascular events occurred at a similar rate to control subjects. As the first autologous cellular immunotherapy to demonstrate an improvement in overall survival in asymptomatic or minimally symptomatic mCRPC patients, sipuleucel-T represents a new treatment paradigm in oncology.

Topics: Acid Phosphatase; Animals; Antigen-Presenting Cells; Antigens, Neoplasm; Cancer Vaccines; Clinical Trials, Phase III as Topic; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Immunotherapy; Leukocytes, Mononuclear; Male; Neoplasm Metastasis; Prostate; Prostatic Neoplasms; Protein Tyrosine Phosphatases; Tissue Extracts

The improved survival with sipuleucel-T, an autologous antigen-presenting cell-based agent, for the treatment of patients with metastatic asymptomatic and minimally symptomatic castration-resistant prostate cancer supports immunotherapy as a valid approach. Also, multiple novel immunotherapeutic approaches are undergoing vigorous investigation. T-lymphocyte checkpoint blockade and poxvirus-based prime-boost approaches are in phase III evaluation. Other immunotherapeutic platforms undergoing early investigation include radioimmunoconjugates and adenovirus-based, DNA-based, and Listeria-based approaches. The development of predictive markers for immune response that translate into improved long-term outcomes is important. This article reviews the emerging data and the unique strengths and weaknesses of these approaches.

Topics: Acid Phosphatase; Biomarkers, Tumor; Cancer Vaccines; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Immunotherapy; Listeria monocytogenes; Male; Neoplasms, Hormone-Dependent; Prostatic Neoplasms; Randomized Controlled Trials as Topic; Recombinant Fusion Proteins; Tissue Extracts

Adenoid cystic carcinoma is an unusual histological variant of prostatic carcinoma. Because of its rarity, the natural history of this tumor is not known. Here we report this rare entity in a 62-year-old man who presented with symptoms of urinary tract obstruction. Digital rectal examination and ultrasonography (USG) showed an enlarged hard nodular prostate. Serum prostate-specific antigen (PSA) and prostatic acid phosphate levels were found to be within the normal range. Transrectal ultrasound-guided 12 core biopsies of prostate showed morphological features of an adenoid cystic carcinoma in 8 cores (bilateral, mid and base) on histopathological examination. Immunohistochemistry performed for PSA on paraffin section was negative. After diagnosis, bilateral orchidectomy was performed, and hormonal therapy was started in the form of androgen receptor blocker. The patient was clinically stable during a limited follow up of six months.

Topics: Acid Phosphatase; Androgen Antagonists; Biomarkers; Biopsy; Carcinoma, Adenoid Cystic; Chemotherapy, Adjuvant; Digital Rectal Examination; Humans; Immunohistochemistry; Male; Middle Aged; Orchiectomy; Prostate-Specific Antigen; Prostatic Neoplasms; Protein Tyrosine Phosphatases; Treatment Outcome

As the most common malignancy among North American males, prostate cancer causes more than 30,000 deaths each year. After local and hormonal treatments, a great number of patients ultimately progressed to castrate-resistant prostate cancer (CRPC), in which chemotherapy provides a small survival advantage, but with significant toxicities. In the past decade, prostate cancer has become a target for several immunotherapeutic approaches. Sipuleucel-T (Provenge®, or APC8015) is a novel cancer vaccine developed from autologous dendritic cells (DC) loaded with engineered fusion protein of prostatic acid phosphatase (PAP) and granulocyte-macrophage colony-stimulating factor (GM-CSF). Phase I and Phase II trials show that the vaccine is safe and effective in creating immune responses toward the fusion-protein target antigen, PAP-GM-CSF also call PA2024. Recent Phase III studies also demonstrated sipuleucel-T's efficacy in prolonging median survival in patients with CRPC, despite little or no effect on clinical disease progression or surrogates such as serum PSA kinetics. Subsequently, the United States Food and Drug Administration approved sipuleucel-T for the treatment of asymptomatic or minimally symptomatic CRPC in April 2010. Filings are projected with international regulatory agencies in 2011. While the development of sipuleucel-T provides an option for patients with early CRPC, it also introduces physicians and researchers to new unanswered questions regarding its optimal clinical use and questions about mechanism of action and combination and sequencing with other agents.

Topics: Acid Phosphatase; Cancer Vaccines; Dendritic Cells; Disease Progression; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Immunotherapy, Active; Kaplan-Meier Estimate; Male; Prostatic Neoplasms; Protein Tyrosine Phosphatases; Tissue Extracts

Prostatic acid phosphatase (PAP) is the most abundant phosphatase in human prostate tissue/secretions. It is a clinically important protein for its relevance as a biomarker of prostate carcinoma. Furthermore, it has a potential role in fertilization. We describe here most of the features of PAP including gene regulation, gene/protein structure, functions, its role in tumor progression and evolutionary features. PAP has phosphatase activity and is an extensively studied biomarker of prostate cancer. The major action of PAP is to dephosphorylate macromolecules with the help of catalytic residues (His(12) and Asp(258)) that are located in the cleft between two domains. This article will be of great interest to all those scientists who are working in the area of prostate pathophysiology.

Topics: Acid Phosphatase; Adenocarcinoma; Amino Acid Sequence; Androgens; Animals; Biomarkers, Tumor; Catalytic Domain; Enzyme Induction; Female; Fertilization; Humans; Male; Mammals; Models, Molecular; Molecular Sequence Data; Placenta; Pregnancy; Prostate; Prostatic Neoplasms; Protein Conformation; Protein Structure, Tertiary; Protein Tyrosine Phosphatases; Semen; Sequence Alignment; Sequence Homology, Amino Acid; Structure-Activity Relationship

Dendritic cells (DCs) are professional antigen-presenting cells (APCs), which display an extraordinary capacity to induce, sustain, and regulate T-cell responses providing the opportunity of DC-based cancer vaccination strategies. Thus, clinical trials enrolling prostate cancer patients were conducted, which were based on the administration of DCs loaded with tumor-associated antigens. These clinical trials revealed that DC-based immunotherapeutic strategies represent safe and feasible concepts for the induction of immunological and clinical responses in prostate cancer patients. In this context, the administration of the vaccine sipuleucel-T consisting of autologous peripheral blood mononuclear cells including APCs, which were pre-exposed in vitro to the fusion protein PA2024, resulted in a prolonged overall survival among patients with metastatic castration-resistant prostate cancer. In April 2010, sipuleucel-T was approved by the United States Food and Drug Administration for prostate cancer therapy.

Topics: Acid Phosphatase; Animals; Antigen-Presenting Cells; Antigens, Neoplasm; Cancer Vaccines; Clinical Trials as Topic; Dendritic Cells; Drug Approval; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Immunotherapy, Adoptive; Lymphocyte Activation; Male; Prostatic Neoplasms; Recombinant Fusion Proteins; Tissue Extracts; United States

The prostate gland secretes many proteins in a prostatic fluid that combines with seminal vesicle derived fluids to promote sperm activation and function. Proximal fluids of the prostate that can be collected clinically are seminal plasma and expressed-prostatic secretion (EPS) fluids. EPS represents the fluid being secreted by the prostate following a digital rectal prostate massage, which in turn can be collected in voided urine post-exam. This collection is not disruptive to a standard urological exam, and it can be repeatedly collected from men across all prostatic disease states. A direct EPS fluid can also be collected under anesthesia prior to prostatectomy. While multiple genetic assays for prostate cancer detection are being developed for the shed epithelial cell fraction of EPS urines, the remaining fluid that contains many prostate-derived proteins has been minimally characterized. Approaches to optimization and standardization of EPS collection consistent with current urological exam and surgical practices are described, and initial proteomic and glycomic evaluations of the of EPS fluid are summarized for prostate specific antigen and prostatic acid phosphatase. Continued characterization of the prostate specific protein components of EPS urine combined with optimization of clinical collection procedures should facilitate discovery of new biomarkers for prostate cancer.

Topics: Acid Phosphatase; Biomarkers; Body Fluids; Electrophoresis, Gel, Two-Dimensional; Epithelial Cells; Gene Expression Regulation, Neoplastic; Glycomics; Humans; Male; Prostate; Prostatic Diseases; Prostatic Neoplasms; Protein Tyrosine Phosphatases; Proteomics; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Time Factors

Prostatic acid phosphatase (PAP) emerged as the world's first clinically useful tumor marker in the 1940s and 1950s. With the introduction of the prostate-specific antigen (PSA) test in the 1980s, which performed significantly better than PAP in terms of screening and monitoring response to treatment, PAP fell into disfavor. An increasing number of recent studies have identified PAP as a significant prognostic factor for patients with intermediate- and high-risk prostate cancer. PAP appears to be particularly valuable in predicting distant failure in higher-risk patients for whom high levels of local control are achieved with aggressive initial local treatment. As prostate cancer care becomes increasingly focused on identifying the minority of patients who would benefit from aggressive systemic therapy, a reevaluation of the potential contribution of the prostatic acid phosphatase test seems timely.

Topics: Acid Phosphatase; Biomarkers, Tumor; Humans; Male; Neoplasm Staging; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Protein Tyrosine Phosphatases

Topics: Acid Phosphatase; Biomarkers, Tumor; Humans; Male; Prostatic Hyperplasia; Prostatic Neoplasms; Protein Tyrosine Phosphatases; Radioimmunoassay; Reagent Kits, Diagnostic; Reference Values; Specimen Handling

Human prostatic acid phosphatase (PAcP) was used as a valuable surrogate marker for monitoring prostate cancer prior to the availability of prostate-specific antigen (PSA). Even though the level of PAcP is increased in the circulation of prostate cancer patients, its intracellular level and activity are greatly diminished in prostate cancer cells. Recent advances in understanding the function of the cellular form of PAcP (cPAcP) have shed some light on its role in prostate carcinogenesis, which may have potential applications for prostate cancer therapy. It is now evident that cPAcP functions as a neutral protein tyrosine phosphatase (PTP) in prostate cancer cells and dephosphorylates HER-2/ErbB-2/Neu (HER-2: human epidermal growth factor receptor-2) at the phosphotyrosine (p-Tyr) residues. Dephosphorylation of HER-2 at its p-Tyr residues results in the down-regulation of its specific activity, which leads to decreases in growth and tumorigenicity of those cancer cells. Conversely, decreased cPAcP expression correlates with hyperphosphorylation of HER-2 at tyrosine residues and activation of downstream extracellular signal-regulated kinase (ERK)/mitogen activated protein kinase (MAPK) signaling, which results in prostate cancer progression as well as androgen-independent growth of prostate cancer cells. These in vitro results on the effect of cPAcP on androgen-independent growth of prostate cancer cells corroborate the clinical findings that cPAcP level is greatly decreased in advanced prostate cancer and provide insights into one of the molecular mechanisms involved in prostate cancer progression. Results from experiments using xenograft animal models further indicate a novel role of cPAcP as a tumor suppressor. Future studies are warranted to clarify the use of cPAcP as a therapeutic agent in human prostate cancer patients.

Topics: Acid Phosphatase; Androgens; Cell Proliferation; Epithelium; Humans; Male; Prostatic Neoplasms; Protein Tyrosine Phosphatases; Receptor, ErbB-2; Tumor Suppressor Proteins

PSA continues to be one of the most effective and widely used cancer screening tools available. Its popularity in prostate cancer screening, however, has eroded its usefulness in the staging of this disease. As more men are screened every year on a routine basis with DRE and PSA, the average PSA at diagnosis has drifted down to well below 10 ng/mL in many centers, including ours. This trend is likely to accelerate, as a PSA cut off for prompting biopsy of the prostate of 2.5 ng/mL gains more widespread acceptance. The recent realization that, at these levels, serum PSA is more reflective of the presence of BPH than of the extent of cancer and, therefore, does not provide additional staging information, has renewed the search for new biochemical markers that are capable of predicting prostate cancer stage and prognosis. Because of the heterogeneity of this disease, it is unlikely that a single biochemical marker that is capable of accurately staging all prostate cancer patients will be found. For this reason, nomograms that are capable of integrating various parameters to predict stage and prognosis will remain indispensable. As new biochemical markers that provide independent predictive information about stage or prognosis are identified, they can be incorporated into currently available nomograms. Of the biochemical markers discussed in this article, IL-6sR and TGF-beta1 are the most promising. By incorporating them into a preoperative nomogram designed to predict PSA recurrence, we found that they improved the ability to predict biochemical recurrence by a statistically and clinically significant margin. The ability to stage prostate cancer and predict response to therapy has improved dramatically over the last 3 decades. Nevertheless, there is still a need for new biochemical markers that will improve the ability to predict an individual patient's stage and response to therapy. Incorporating these new markers into nomograms will enhance the ability to provide optimal care for each prostate cancer patient.

Topics: Acid Phosphatase; Humans; Insulin-Like Growth Factor Binding Protein 2; Insulin-Like Growth Factor Binding Protein 3; Interleukin-6; Male; Neoplasm Staging; Polymerase Chain Reaction; Predictive Value of Tests; Prognosis; Prostate-Specific Antigen; Prostatic Neoplasms; Protein Tyrosine Phosphatases; Receptors, Interleukin-6; Tissue Kallikreins; Transforming Growth Factor beta; Transforming Growth Factor beta1

While androgen deprivation has remained the cornerstone of therapy for advanced prostate cancer over the last 60 years, novel therapies are being developed that may expand upon currently available treatments. The identification of antigens expressed by prostate tissue and/or prostate cancer that are recognized by T cells creates opportunities to develop novel immunotherapeutic approaches, including tumor vaccines. Improved understanding of immune recognition and antigen presentation may lead to effective immunotherapies for prostate cancer. Identified proteins expressed in prostate cancer, including prostate-specific antigen (PSA), prostatic acid phosphatase (PAP), and prostate-specific membrane antigen (PSMA), have been used as immunologic targets for immunotherapy. Moreover, innovations in cancer genomics and proteomics will also aid in the identification of immunologic targets. Immunotherapy trials have already demonstrated evidence of not only immunogenicity, but also clinical efficacy, and future studies will be directed at capitalizing on these findings.

Topics: Acid Phosphatase; Adjuvants, Immunologic; Antigen Presentation; Antigens, Neoplasm; Antigens, Surface; Biomarkers, Tumor; Cancer Vaccines; Forecasting; Genomics; Glutamate Carboxypeptidase II; Humans; Immunogenetics; Immunotherapy; Male; Prostate-Specific Antigen; Prostatic Neoplasms; Protein Tyrosine Phosphatases; T-Lymphocytes; Treatment Outcome

Carcinoma of the prostate represents one of the most frequently diagnosed cancers in men. If detected at an early stage, prostate cancer is highly treatable. However, cancers identified at a late stage are rarely cured with contemporary medical therapies. Early detection strategies presently center on the identification of prostate-specific proteins in the serum, and emerging therapeutics have utilized genes and proteins with prostate-restricted expression for tissue-selective immunological regimens incorporating vaccines, dendritic cell therapy, gene therapy, and antibody-based cell targeting. In order to develop improved therapeutic procedures, efforts have been directed toward the identification of genes exhibiting prostate-restricted expression profiles, or altered expression levels in neoplastic cells relative to their normal counterparts. Comprehensive expression profiling approaches such as the analysis of oligonucleotide- or complementary DNA (cDNA)-microarrays have greatly enhanced these efforts. Genes and their cognate proteins identified using such methods offer additional diagnostic and therapeutic targets that may aid in the understanding and treatment of prostate carcinoma.

Topics: Acid Phosphatase; Antigens, Surface; Carboxypeptidases; Gene Expression Profiling; Glutamate Carboxypeptidase II; Humans; Immunotherapy; Male; Oligonucleotide Array Sequence Analysis; Prostate-Specific Antigen; Prostatic Neoplasms; Protein Tyrosine Phosphatases; Testosterone Congeners

Dendreon (formerly Activated Cell Therapy), in association with the Mayo Clinic, is developing the dendritic cell therapy APC-8015 (Provenge) for the potential treatment of hormone-refractory prostate cancer [284376]. Phase III trials were initiated in January 2000 [353557], and in July 2001 Dendreon anticipated that preliminary results would be available by the end of the year [417283], [427591]. As of September 2001, Dendreon was planning tofile a BLA in 2002 [421356]. Provenge involves the use of a proprietary recombinant antigen derived from prostatic acid phosphatase, found in approximately 95% of prostate cancers. The target antigen is combined with the patient's own dendritic cells and reinfused into the patient to stimulate an immune response [406383]. In November 1999, Dendreon received US-05976546, which covers the composition of the prostate tumor antigen engineered by Dendreon to help stimulate the immune system [347885]. In August 2000, Dendreon received US-06080409, entitled 'Immunostimulatory composition', which relates to the method by which Dendreon's vaccines stimulate the T-cell arm of the immune system tofight cancer [379085]. In April 2001, Dendreon was awarded US-06210662 covering the therapeutic composition of APC-8015 [406383].

Topics: Acid Phosphatase; Antigen Presentation; Antigens, Neoplasm; Cancer Vaccines; Clinical Trials as Topic; Dendritic Cells; Humans; Male; Prostatic Neoplasms; Protein Tyrosine Phosphatases; T-Lymphocytes

Acid phosphatases (APs) are a family of enzymes that are widespread in nature, and can be found in many animal and plant species. Mystery surrounds the precise functional role of these molecular facilitators, despite much research. Yet, paradoxically, human APs have had considerable impact as tools of clinical investigation and intervention. One particular example is tartrate resistant acid phosphatase, which is detected in the serum in raised amounts accompanying pathological bone resorption. This article seeks to explore the identity and diversity of APs, and to demonstrate the relation between APs, human disease, and clinical diagnosis.

Topics: Acid Phosphatase; alpha-Macroglobulins; Biomarkers; Bone Resorption; Favism; Gaucher Disease; Humans; Intracellular Fluid; Isoenzymes; Leukemia, Hairy Cell; Male; Osteoclasts; Osteoporosis; Prostate; Prostatic Neoplasms; Protein Binding; Reactive Oxygen Species; Tartrate-Resistant Acid Phosphatase

Though prostate specific antigen (PSA) and prostate acid phosphatase (PAP) are of greater value in the postoperative monitoring of patients with cancer of the prostate, high preoperative levels suggest the probability of malignancy. Benign conditions of the prostate are known to raise the serum levels of these enzymes, however, the higher the level of these markers the stronger is the suspicion of malignancy.. This report describes five patients who presented with acute urinary retention and had evidence of prostatic infarction and chronic prostatitis on histology.. The combination of these factors probably accounted for the extremely elevated levels of PSA and PAP as other possible causes were ruled out.

Topics: Acid Phosphatase; Aged; Aged, 80 and over; Biomarkers, Tumor; Biopsy; Diagnosis, Differential; Humans; Infarction; Male; Middle Aged; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Sensitivity and Specificity

Acid phosphatase (ACP) is a hydrolytic lysosomal enzyme secreted by a number of cells including blood cells as well as by the prostate, bones, liver and other tissues. Several isozymes of ACP have tissue specificity. The isozymes can be fractionated by electrophoresis into six bands. Prostatic ACP (bands 2-4) is frequently measured for the diagnosis of prostatic disease. Band 5, tartrate resistant ACP (TRACP) consists of two isoforms, bands 5a and 5b. TRACP 5b is considered to be a marker of the osteoclasts and 5a is found in Gaucher's cells, or in the leukocytes of patients with hairy cell leukemia.

Topics: Acid Phosphatase; Biomarkers; Bone Diseases, Metabolic; Clinical Enzyme Tests; Female; Hematologic Neoplasms; Humans; Isoenzymes; Male; Organ Specificity; Prostatic Neoplasms; Sphingolipidoses; Tartrates

Prostate cancer is a significant health problem and one of the leading causes of cancer-related death among men. Given the typically long natural history of the disease, there is considerable interest in developing new therapies to treat or prevent metastatic disease, and cancer vaccines are a particularly attractive immune-based approach. Early clinical studies using non-specific immunomodulatory treatments have met with limited success, but also suggest that improved immunologic approaches might be useful in treating human prostate cancer. Over the last decade, the identification of immune cells responsible for actual destruction of prostate tissue and advances in immunologic and molecular techniques have led to a variety of vaccination approaches that are currently being evaluated in human clinical trials. The present article discusses the rationale in animal models for particular immunization strategies and describes the vaccines currently being used in patients with prostate cancer. The ongoing identification of tumor antigens and proteins involved in prostate cancer progression and the development of better immunologic animal models suggest a hopeful future for the design of effective prostate cancer vaccines.

Topics: Acid Phosphatase; Animals; Antigens, Surface; Antigens, Tumor-Associated, Carbohydrate; Cancer Vaccines; Carboxypeptidases; Dendritic Cells; Disease Models, Animal; Glutamate Carboxypeptidase II; Humans; Male; Mice; Neoplasms, Experimental; Prostate-Specific Antigen; Prostatic Neoplasms; Rats

The anatomic extent of prostate cancer has long served the role of providing prognostic information to assist in therapeutic decision-making, evaluating treatment outcomes, facilitating information exchange between medical centers, and promoting cancer research. However, nonanatomic factors are also associated with important pathological features of this condition and may be used to estimate therapeutic outcome. At present, tumor grade (eg, Gleason score) ascertained from the diagnostic biopsy specimen and the pretherapy serum prostate-specific antigen level are readily available in clinical practice. This information may be used along with clinical tumor stage to construct predictive models. These models may provide reliable estimates for the likelihood of extraprostatic tumor extension, seminal vesicle invasion, or pelvic lymph-node involvement. Consideration of this information may play a vital role in the selection of radiotherapeutic modality and in the definition of external beam radiotherapy treatment volumes. These same factors are also associated with disease relapse and may be combined in a fashion to estimate the prospects for cancer control in the individual patient and in homogeneous patient groups. Grouping patients according to the risk for and site of disease recurrence may be instrumental in the development of clinical trials that assess therapeutic approaches in appropriate subsets of patients.

Topics: Acid Phosphatase; Clinical Trials as Topic; DNA, Neoplasm; Humans; Lymphatic Metastasis; Male; Multivariate Analysis; Neoplasm Invasiveness; Neoplasm Staging; Patient Selection; Prognosis; Prostate-Specific Antigen; Prostatic Neoplasms; Research Design; Risk Factors; Seminal Vesicles

Topics: Acid Phosphatase; Amino Acid Sequence; Animals; Enhancer Elements, Genetic; Gene Expression Regulation; Glycoproteins; Humans; Male; Molecular Sequence Data; Promoter Regions, Genetic; Prostate-Specific Antigen; Prostatic Neoplasms; Prostatic Secretory Proteins; Proteins; Seminal Plasma Proteins

Topics: Acid Phosphatase; Biomarkers, Tumor; Humans; Male; Prostate; Prostatic Neoplasms

The detection and treatment of prostate cancer has been markedly improved by the use of Prostate-Specific Antigen (PSA) as a serological biomarker for disease. However, even after surgical intervention and hormone ablation therapy, a significant proportion of patients progress to advanced metastatic disease, for which there is no cure. An important goal has become the identification of antigens in advanced stage prostate cancer that represent targets for therapy. Recently, great progress has been made to utilize immunological therapies to treat cancer. Monoclonal antibody therapy has been successfully approved for the treatment of breast cancer and B-cell lymphoma, and multiple clinical trails are currently in progress in a variety of cancers, including prostate cancer. Pre-clinical and clinical studies are also underway to evaluate cancer vaccine approaches directed against antigens that are highly expressed in prostate and other cancers. This article describes several target antigens expressed in prostate cancer and immunological approaches directed against them that may be effective for treating prostate cancer patients.

Topics: Acid Phosphatase; Animals; Antibodies, Monoclonal; Antigens, Neoplasm; Cancer Vaccines; Humans; Immunotherapy; Male; Prostate-Specific Antigen; Prostatic Neoplasms

The incidence and mortality of prostate cancer are increasing at alarming rates, partially due to an aging population. Early detection of prostate cancer, using clinically sensitive procedures and/or tumor markers (e.g., prostate-specific antigen [PSA]), is of prime importance. However, the choice of therapeutic interventions for prostate cancer at the time of diagnosis is largely dependent on clinical and pathologic staging and prediction of the degree of aggressiveness of the disease. Clinically applicable prognostic markers are urgently needed to assist in the selection of optimal therapy.. Literature review of the potential diagnostic and prognostic markers for human prostate cancer.. Well-established tissue prognostic indicators, including histologic grade, margin positivity, pathologic stage, intraglandular tumor extent, and DNA ploidy, are not reviewed in this paper. Recently, a number of novel markers have been identified. In this paper, we begin with a discussion of a number of well-established as well as investigational diagnostic markers and then focus on evaluation of prognostic markers. Diagnostic markers that have prognostic value and investigational prognostic markers are also discussed.. Currently, only PSA is utilized for early diagnosis and monitoring of prostate cancer. A number of potential prognostic markers warrant further investigation. Multimarker analysis is implicated.

Topics: Acid Phosphatase; Antigens, Neoplasm; Antigens, Surface; Biomarkers, Tumor; Genes, p53; Glutamate Carboxypeptidase II; Humans; Male; Prognosis; Prostate-Specific Antigen; Prostatic Neoplasms

Topics: Acid Phosphatase; Adult; Aged; Biopsy, Needle; Humans; Male; Middle Aged; Palpation; Prostate-Specific Antigen; Prostatic Hyperplasia; Prostatic Neoplasms; Ultrasonography

The acid phosphatases are a group of enzymes capable of hydrolyzing esters of orthophosphoric acid in an acid medium. Acid phosphatase activity is widely distributed in human tissues and acid phosphatases represent a heterogeneous group of enzymes containing many isoenzymes, each specific for one type of tissue. The human prostate is particularly rich in this enzyme (PAP) and serum enzyme levels have been used as a tumor marker of prostate cancer. While PAP was markedly increased in patients with bone metastases of prostate cancer, it is unable to detect earlier stage tumors reliably. The sensitivity and specificity of serum acid phosphatases and PAP are low in diagnosing, staging and following patients with prostate cancer. Presently, prostate-specific antigen (PSA) is superior to PAP for diagnosis, screening, and monitoring prostate cancer. PAP may have an adjuvant value in the management of prostate cancer because a combination of PSA and PAP testing has revealed a high sensitivity and specificity in detecting prostate cancer.

Topics: Acid Phosphatase; Clinical Enzyme Tests; Humans; Isoenzymes; Male; Prostatic Neoplasms; Radioimmunoassay

Topics: Acid Phosphatase; Biomarkers, Tumor; Humans; Male; Prostatic Neoplasms

Topics: Acid Phosphatase; Biomarkers, Tumor; Humans; Immunohistochemistry; Keratins; Male; Prognosis; Prostate; Prostate-Specific Antigen; Prostatic Hyperplasia; Prostatic Neoplasms

Topics: Acid Phosphatase; Age Factors; Biomarkers, Tumor; Forecasting; Humans; Male; Neoplasm Staging; Predictive Value of Tests; Prognosis; Prostate-Specific Antigen; Prostatic Neoplasms; Risk Factors; Severity of Illness Index

An 80-year-old man, who had been treated for colon cancer 25 years ago, presented with gross hematuria. Rectal examination revealed a soft nodule in the right lobe. The serum prostatic specific antigen (PSA) was elevated to 5.2 ng/ml, while prostatic acid phosphate (PAP) was normal. Transrectal ultrasound revealed a hypoechoic mass in peripheral zone of the prostate and dilated seminal vesicle. A needle biopsy of the prostate showed mucinous adenocarcinoma. Under the diagnosis of prostatic tumor with seminal vesicle involvement, radical prostatectomy was performed. Histological findings showed organ confined cancer, of which most was composed of extracellular mucin lakes. Immunohistochemical study revealed the tumor cells positive for PSA and PAP. Mucinous adenocarcinoma of the prostate has been known to be clinically different from non-mucinous adenocarcinoma, in that the former is insensitive to hormonal therapy, is rarely associated with elevated PAP and rarely metastasize to the bone. But our analysis of the literatures is Japan showed no significant difference clinically between mucinous and non mucinous prostatic adenocarcinoma. However mucinous adenocarcinoma with signet ring cell rarely responds to hormonal therapy, which should not be classified to true mucinous adenocarcinoma in the current criteria. True mucinous adenocarcinoma could be a variant of prostatic adenocarcinoma, which is peripheral origin and should be treated like non-mucinous adenocarcinoma.

Topics: Acid Phosphatase; Adenocarcinoma, Mucinous; Aged; Aged, 80 and over; Biomarkers, Tumor; Diagnosis, Differential; Humans; Immunohistochemistry; Male; Prostate-Specific Antigen; Prostatic Neoplasms

Our knowledge of prostate cancer is less well-defined than our knowledge of cancers of other organs. In the colon, for example, morphological criteria to identify carcinomas in situ and some putative preneoplastic lesions are clear; phenotypic differences in the expression of enzymes and antigens are documented in experimental models and are starting to be defined in humans. Experimental models of cancer of the liver and colon show evidence that "enzyme-altered foci" are preneoplastic. In these organs, the "normal" context is much clearer than in the prostate. In contrast, in the prostates of men in the same age range as those who develop prostate cancer, morphological aberrations are almost always present, diverse, and poorly understood. Murphy and Gaeta said that, "in the study of prostatic disease..., almost every aspect remains controversial...[and].... many of the 'known facts' concerning prostatic disease are poorly documented..." While being aware that the definitions of all benign and malignant lesions of the prostate are based on complex morphological criteria which must form the contemporary context for comparisons, our laboratory is searching for markers that will permit the identification of putative preneoplastic lesions in the prostate. In our opinion, these changes will not be found most efficiently, if they are present at all, in long established cell lines, advanced carcinomas, or serially transplantable xenografts of primary prostatic carcinomas. Our preliminary data suggest that several enzyme histochemical and immunohistochemical approaches are worthy of study. Markers that show promise include acid phosphatase, 5'-nucleotidase, leucine aminopeptidase, and CD44.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: 5'-Nucleotidase; Acid Phosphatase; Adult; Aged; Aged, 80 and over; Aging; Animals; Antigens, CD; Biomarkers, Tumor; Carcinoma in Situ; Carrier Proteins; Humans; Hyaluronan Receptors; Leucyl Aminopeptidase; Male; Middle Aged; Organ Size; Precancerous Conditions; Prostate; Prostatic Neoplasms; Receptors, Cell Surface; Receptors, Lymphocyte Homing

Human prostatic acid phosphatase (EC 3.1.3.2) is a non-specific phosphomonoesterase, synthetized and secreted into seminal plasma under androgenic control. The enzyme is a dimer of molecular weight around 100 kDa. Gene coding this protein is localized on chromosome 3. Since many years prostatic phosphatase has been used as a marker of diagnosis and therapy control of cancer of the prostate gland. The biological role of this enzyme, however, remains unknown and needs further exploration.

Topics: Acid Phosphatase; Adenocarcinoma; Biomarkers, Tumor; Clinical Enzyme Tests; Humans; Male; Prostate; Prostatic Neoplasms

To review the efficacy of the combination of the anti-androgen nilutamide (Anandron) plus orchidectomy in patients with stage D prostate cancer who had received no previous treatment.. The results of seven randomized double-blind trials were analysed. In these studies patients were followed up until progression of disease or withdrawal for other reasons. Bone pain, urinary symptoms, performance status, levels of prostatic acid phosphatase (PAP) and alkaline phosphatase (AP) were evaluated before treatment and after 1, 3, 6, 12 and 18 months of treatment. Bone scans and X-rays were taken every 6 months. The best objective response, the time of progression and the time of death were recorded. The changes from baseline in symptoms and levels of tumour markers at month six and the percentages of objective regressions in the two treatment groups were compared using the Cochran-Mantel-Haenszel test stratified by study. Peto's method was used for the analysis of time to progression and of survival.. Of the 1191 patients enrolled in all the original trials, 1056 were eligible. In the group of patients treated with nilutamide 50% had complete or partial regression of disease compared with 33% of those who were given a placebo (P < 0.001); bone pain and levels of PAP and AP were improved or returned to normal significantly more frequently (P < 0.01); the odds of disease progression were significantly reduced (odds ratio 0.84, P = 0.05); the odds of death from cancer and from other causes were reduced but the difference was not statistically significant.. The combination of nilutamide and orchidectomy has a beneficial effect on pain of metastatic origin, levels of tumour markers, the objective response of disease and the time to disease progression. This treatment combination might also improve survival.

Topics: Acid Phosphatase; Alkaline Phosphatase; Androgen Antagonists; Antineoplastic Agents; Biomarkers, Tumor; Bone Neoplasms; Combined Modality Therapy; Double-Blind Method; Humans; Imidazoles; Imidazolidines; Male; Odds Ratio; Orchiectomy; Prostate; Prostatic Neoplasms; Randomized Controlled Trials as Topic

Androgen deprivation therapy is the initial treatment choice for metastatic disease. When enrolling patients into androgen deprivation trials, it is important to consider stratification of enrollees based on prognostic factors that have been identified as important in determining the likelihood of response. Prognostic factors are also helpful in identifying which patients are less likely to respond to treatment; this information also would help to counsel patients. Performance status is an important prognostic factor; however, its impact is minimal because the great majority of men who receive treatment for advanced disease have a normal performance status. Hemoglobin, alkaline phosphatase, and a semiquantitative grading scale for the number of metastatic foci on the bone scan are useful prognostic factors. The pretreatment serum testosterone level is a powerful prognostic factor. Patients with a low serum testosterone level have a shorter progression-free survival than men whose pretreatment serum testosterone level is above normal. The prognostic importance of pretreatment serum testosterone level has been evaluated in studies using treatment methods that lower this level to castrate levels. Recently, we found that serum testosterone level was not a prognostic factor for men taking the nonsteroidal antiandrogen, Casodex (Zeneca, Wilmington, DE), which does not alter the serum testosterone level. The pretreatment serum prostatic-specific antigen also is a prognostic factor. This antigen may be the best single method for monitoring patients in regard to response to or progression following therapy. The return of the prostatic-specific antigen level to normal (< 4 ng/ml), or the decline in the prostatic-specific antigen level of > 90% indicates a prolonged progression-free survival. In the future, it will be interesting to incorporate both the initial prognostic factors as well as monitor the prostatic-specific antigen into a multivariate analysis, which will be highly predictive of a man's response to treatment.

Topics: Acid Phosphatase; Humans; Male; Neoplasm Metastasis; Prognosis; Prostate-Specific Antigen; Prostatic Neoplasms; Randomized Controlled Trials as Topic; Testosterone

This article describes the immunoreactivity of PSA and PAP in non-neoplastic and neoplastic prostate tissue. Listed are examples of cross reactivity of PSA and PAP in non-neoplastic and neoplastic tissue from other organs. The use of PSA and PAP to identify tumors of prostatic origin in different sites is also described. Finally, the diagnostic uses of immunohistochemistry for PSA and PAP in prostate biopsies and for prognostication are discussed.

Topics: Acid Phosphatase; Biomarkers, Tumor; Humans; Immunohistochemistry; Male; Prognosis; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Sensitivity and Specificity

In this article, the pathologic findings of carcinoma of the prostate were reviewed. Criteria were discussed for the pathologic diagnosis of prostatic carcinoma (PC), premalignant lesions, lesions that simulate PC, immunopathologic findings, special types of PC, effects of therapy on the prostate, and recent efforts to improve diagnostic and prognostic capabilities. The possible role of the study of nucleolar organizing regions was reported. A new method for demonstrating chromosomes in formaldehyde-fixed paraffin-embedded tissue was mentioned. The need for research in all aspects of the pathology of prostatic cancer was emphasized.

Topics: Acid Phosphatase; Cell Nucleus; Humans; Male; Neoplasm Invasiveness; Neoplasm Staging; Precancerous Conditions; Prognosis; Prostate; Prostate-Specific Antigen; Prostatic Hyperplasia; Prostatic Neoplasms

An obvious advantage of a combined PAP and PSA measurement is the increased sensitivity of detection. Furthermore, the use of both markers in monitoring patients with prostatic carcinoma offers the advantage of a greater number of patients with objective parameters for follow-up.

Topics: Acid Phosphatase; Biomarkers, Tumor; Humans; Isoenzymes; Male; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms

We report an uncommon case of primary prostatic signet-ring cell carcinoma which meets all criteria that define this clinicopathologic entity. Histologically, the tumor showed three different growth patterns, all of which contained large numbers of signet-ring cells. The predominant pattern, comprising approximately 50 percent of the tumor, was solid sheets of pure signet-ring cells. An intriguing finding was the presence of intestinal metaplasia involving the prostatic urethra and the large periurethral ducts. All mucin stains were intensely positive within the signet-ring cells and in the mucin lakes. Signet-ring cells stained positively for prostatic specific antigen, prostatic acid phosphatase, and carcinoembryonic antigen immunoperoxidase markers. Our patient presented with symptoms of urinary tract obstruction and locally widespread disease, infiltrating the rectum and the bladder, thus demonstrating the aggressive biologic behavior that traditionally has been ascribed to signet-ring cell carcinomas.

Topics: Acid Phosphatase; Adenocarcinoma, Mucinous; Carcinoembryonic Antigen; Humans; Immunohistochemistry; Male; Middle Aged; Mucins; Neoplasm Invasiveness; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms

Approximately 30 years ago, the finding that prostate acid phosphatase (PAP) was antigenically distinct from other acid phosphatases opened an era in the measurement of prostate cancer. Many immunoassays have been developed but their clinical significance has been limited. Studies comparing one or more assays in the same population of men with prostate cancer population have concluded that no differences were found in the sensitivities of the assays when the upper limits of normal were selected to provide equal specificities.

Topics: Acid Phosphatase; Biomarkers, Tumor; Humans; Isoenzymes; Male; Methods; Prostatic Neoplasms

The principal role of PAP determinations in 1993 with the ready availability of reproducible serum PSA determinations would be in the identification of those patients with clinically localized prostate cancer who will not be candidates for surgical cure because of the high likelihood of having pathologic stage C or D disease. However, if you believe that radical prostatectomy offers good local control and palliation for clinically localized but pathologic stage C or D disease, then preoperative PAP determinations are not necessary. Also, if you believe that radical prostatectomy in conjugation with androgen deprivation therapy is appropriate for clinically localized but pathologic stage D1 disease, then, again, preoperative PAP determinations are not necessary. However, if you believe that radical prostatectomy is indicated only for those patients with organ-confined cancer, then ordering a preoperative staging Roy enzymatic PAP assay is indicated. Therefore, every urologist must know the type of assay and the substrate being used by his/her laboratory to interpret the PAP results properly; otherwise, patients with potentially curable cancer will not be offered a radical prostatectomy. In conclusion, PSA is superior to PAP for diagnosis, screening, and monitoring prostate cancer. Even though there are three assays for PSA, there is less confusion in interpreting the results than for PAP. The only specific area where the enzymatic PAP assay can be useful is in the identification of those patients with clinically localized disease but pathologically extensive disease; this is not important if you believe that radical prostatectomy offers good local control and palliation for pathologic stage C and D1 disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acid Phosphatase; Biomarkers, Tumor; Humans; Male; Prostatic Neoplasms

Carcinoma of the prostate has become one of the top ten malignancies in Singapore but to date, there has been little local clinical data available on the disease. This study aims to establish the clinical profile of Stage D carcinoma of the prostate in the local population. Forty-seven patients with Stage D disease treated by the department over a ten-year period, 1981-90, were studied. The majority (47.7%) fell in the age-group 66-75 years and the most common presenting symptom was bone pain (36.2%). Both acid and alkaline phosphatases were found to be poor diagnostic markers of the extent of the disease. Acid phosphatase was not elevated in 25.0% and alkaline phosphatase not elevated in 39.1% of our patients. Forty of these patients had orchidectomy and of these, ten were also treated with oral stilbesterol. Five-year survival for the orchidectomy group was 22.7% and that for the orchidectomy-plus-stilbesterol group was 23.0%. This compares well with other studies done in the West. Eight patients died within the first year of diagnosis but of those who survived, all remained symptom-free within this first year. The proportion of those who remained symptom-free fell to 25.0% of the survivors for subsequent years.

Topics: Acid Phosphatase; Age Factors; Aged; Aged, 80 and over; Alkaline Phosphatase; Combined Modality Therapy; Diethylstilbestrol; Humans; Male; Middle Aged; Neoplasm Staging; Orchiectomy; Prognosis; Prostatectomy; Prostatic Neoplasms; Registries; Retrospective Studies; Singapore; Survival Rate; Treatment Outcome

Histochemistry, including immunohistochemistry, is helpful to the practicing pathologist in the diagnosis of prostatic carcinoma. Of equal importance, histochemistry is being increasingly used to study the pathobiology of the prostate. This article reviews these histochemical techniques and their applications.

Topics: Acid Phosphatase; Antigens, Neoplasm; Biomarkers, Tumor; Blood Group Antigens; Histocytochemistry; Humans; Keratins; Lectins; Male; Mucins; Prostate-Specific Antigen; Prostatic Neoplasms; Receptors, Steroid

A very rare case of carcinosarcoma of the prostate is reported. The patient was a 77-year-old man in whom both primary and metastatic tumors presented the pathology of carcinosarcoma of the prostate. The carcinosarcoma was resistant to anti-androgen therapy, and the patient showed low level of serum prostatic acid phosphatase and was free from bony metastases despite multiple metastases to the lung, liver, pancreas, para-aortic lymph nodes, spleen and penis. The sarcomatous component consisted of chondrosarcoma and fibrosarcoma, both of which were positive for vimentin. The carcinomatous component was positive for both keratin and prostatic acid phosphatase.

Topics: Acid Phosphatase; Aged; Carcinosarcoma; Humans; Immunohistochemistry; Keratins; Male; Prostatic Neoplasms

Prostatic specific antigen (PSA) is a tissue specific marker that is now the most widely used biochemical test for the assessment and follow-up of prostate cancer. The levels of PSA rise with tumor stage, but there is considerable overlap of their distribution between stages. PSA measurement now forms a part of the workup of a suspected carcinoma of the prostate, with a level of more than 4 ng/ml being an indication for further investigation. The sensitivity of PSA makes it an essential test for the postoperative assessment of radical prostatectomy and curative radiation therapy. The rates of change of PSA levels in locally advanced and metastatic disease treated by hormone manipulation can provide prognostic information. Low levels of PSA (less than 10 ng/ml) 6 months after treatment are a sign that the response will be prolonged. However, the sensitivity of PSA often results in a rising level preceding clinical evidence of progression by several months and is not necessarily an indication to change treatment. Alkaline phosphatase and prostatic acid phosphatase provide a less sensitive test for the bone response to skeletal metastases and tumor activity in advanced disease, respectively.

Topics: Acid Phosphatase; Alkaline Phosphatase; Antigens, Neoplasm; Biomarkers, Tumor; Clinical Enzyme Tests; Humans; Male; Prognosis; Prostate; Prostate-Specific Antigen; Prostatectomy; Prostatic Neoplasms; Sensitivity and Specificity

In this presentation the authors review the pathology of prostatic carcinoma (PCa), and discuss criteria for pathologic diagnosis, premalignant lesions, lesions that simulate PCa, immunopathology, special types of PCa, effects of therapy on the prostate, and recent efforts to improve diagnostic and prognostic capabilities. The possible role of study of nucleolar organizing regions is reported. A new method for demonstration of chromosome in formalin-fixed, paraffin-embedded tissue is presented. The need for research in all aspects of pathology is emphasized.

Topics: Acid Phosphatase; Antigens, Neoplasm; Carcinoma; Diagnosis, Differential; Humans; Immunohistochemistry; Male; Neoplasm Invasiveness; Nucleolus Organizer Region; Prostate; Prostate-Specific Antigen; Prostatic Hyperplasia; Prostatic Neoplasms

Staging of prostatic adenocarcinoma is a systematic classification of the extent of disease based on clinical and pathologic criteria. This classification determines treatment and reflects ultimate expected clinical outcome. The technologic changes in diagnostic modalities need to be incorporated into the staging classification and a better assessment of biologic hazard of each individual tumor needs to be developed to further refine current treatment of prostate cancer.

Topics: Acid Phosphatase; Adenocarcinoma; Antigens, Neoplasm; Biomarkers, Tumor; Humans; Male; Neoplasm Metastasis; Neoplasm Staging; Prognosis; Prostate-Specific Antigen; Prostatic Neoplasms; Ultrasonography

Prostatic acid phosphatase (PAP), prostate-specific antigen (PSA), and beta-microseminoprotein are organ-specific markers. Also Leu-7 may be regarded as an organ-specific marker. The main utilization of PAP and PSA immunostaining is to establish the prostatic origin of a carcinoma. Changes of PAP and PSA immunoreactivity may be correlated with histologic grade of prostatic carcinoma. Keratin expression assessment is useful to identify prostatic basal cells or epithelial secretory cells. Neuroendocrine marker reactivity in prostatic carcinoma seems to be related with increasing histologic grade and tumor progression.

Topics: Acid Phosphatase; Antigens, Differentiation; Antigens, Neoplasm; Biomarkers, Tumor; CD57 Antigens; Humans; Intermediate Filament Proteins; Male; Phosphopyruvate Hydratase; Prognosis; Prostate-Specific Antigen; Prostatic Neoplasms; Prostatic Secretory Proteins; Proteins; Seminal Plasma Proteins; Sensitivity and Specificity

Although PSA is considered to be the true serum marker of prostatic tissue and a valuable indicator for cancer in the gland, knowledge of its significance and limitations is essential to its use for screening, staging, and monitoring CAP. PSA may be used in conjunction with DRE for early detection of CAP. Men with abnormal DRE should have a TRUS with or without biopsy. In men older than 50 years and with negative DRE and PSA < 4 ng/mL, annual evaluations are prudent. In patients with a PSA range of 4.0 to 9.9 ng/mL, high-risk groups such as black males and those with a positive family history should have TRUS. Males with negative DRE in the PSA range of 4.0 to 9.9 ng/mL should have TRUS to evaluate prostate volume and PSAD. Biopsy should be considered in those with PSAD > 0.15. Men with PSA > 10 ng/mL, even in the presence of an enlarged benign prostate, should have multiple directed biopsies under TRUS guidance.

Topics: Acid Phosphatase; Biomarkers, Tumor; Humans; Incidence; Male; Mass Screening; Neoplasm Staging; Prostate-Specific Antigen; Prostatic Hyperplasia; Prostatic Neoplasms; Sensitivity and Specificity

The author compared the tumour markers of hundred virginell prostatic cancer patients. There were investigated the activity of prostatic acid phosphatase (SP) and its isoenzyme (SPP) by enzymatic method (PAP) as well. The concentration of prostatic specific antigen (PSA) was determined too. The sensibility of markers are growing on the row, SP, SPP, PAP, PSA. Summarising the results, the determination of PAP together with PSA seems to be not necessary. Because of the low price of SP, SPP their determinations is indicated in selected cases. Regarding of costs-benefit the author advises selected investigations in different stage and in different indications.

Topics: Acid Phosphatase; Aged; Antigens, Neoplasm; Biomarkers, Tumor; Humans; Male; Middle Aged; Prostatic Neoplasms; Tartrates

PSA is a kallikrein-like, serine protease that is produced exclusively by the epithelial cells of all types of prostatic tissue, benign and malignant. Physiologically, it is present in the seminal fluid at high concentration and functions to cleave the high molecular weight protein responsible for the seminal coagulum into smaller polypeptides. This action results in liquefaction of the coagulum. PSA is also present in the serum and can be measured reliably by either a monoclonal immunoradiometric assay or a polyclonal radioimmunoassay. The calculated half-life of serum PSA ranges from 2.2 to 3.2 days and the metabolic clearance rate of this tumor marker follows first-order kinetics. Digital rectal examination, cystoscopic examination and prostate biopsy all can cause spurious elevations of the serum PSA concentration. Conditions such as bacterial prostatitis and acute urinary retention also can falsely elevate the serum PSA level. Because approximately 25% of the patients with BPH only will have an elevated serum PSA concentration and BPH tissue contributes to this PSA value in a variable manner from patient to patient, it is unlikely that PSA by itself will become an effective screening tool for the early diagnosis of prostate cancer. However, if combined with digital rectal examination and/or transrectal ultrasound it may become a vital part of any early detection program. Prostatic intraepithelial neoplasia also may be associated with moderately elevated serum PSA levels. Although there is a direct correlation between the serum PSA concentration and clinical stage, PSA is not sufficiently reliable to determine the clinical stage on an individual basis. This finding also applies to pathological stage. As a result, the preoperative serum PSA concentration cannot be used to decide whether to recommend radical prostatectomy for potential cure. Low preoperative serum PSA concentrations in patients with previously untreated prostate cancers are predictive of a negative bone scan. Thus, in these select patients a staging bone scintigram may not be necessary. With respect to monitoring patients after definitive therapy, PSA is an exquisitely sensitive tumor marker. Irrespective of the treatment modality (radical prostatectomy, radiation therapy or antiandrogen treatment), PSA reflects accurately the tumor status of the patient and is prognostic of eventual outcome; this tumor marker is capable of predicting tumor recurrence months before its detection by any

Topics: Acid Phosphatase; Adenocarcinoma; Amino Acid Sequence; Antigens, Neoplasm; Biomarkers, Tumor; Humans; Male; Mass Screening; Molecular Sequence Data; Prostate; Prostate-Specific Antigen; Prostatic Hyperplasia; Prostatic Neoplasms

The usefulness of acid phosphatase (PAP) and prostate specific antigen (PSA) is compared. The author concludes that PSA is more sensitive, has better organ specificity, does less diurnal variations and correlates better with tumor which makes PSA superior for staging and monitoring of therapy in prostate cancer.

Topics: Acid Phosphatase; Antigens, Neoplasm; Biomarkers, Tumor; Clinical Enzyme Tests; Humans; Male; Neoplasm Staging; Prostate-Specific Antigen; Prostatic Neoplasms; Sensitivity and Specificity

Prostate-specific antigen (PSA) and DNA ploidy as measured by flow cytometry were compared with conventional prognostic indicators in 112 patients who underwent radical prostatectomy for clinically resectable prostate cancer. The variables examined included age, race, prostatic acid phosphatase (PAP), Gleason score of the radical prostatectomy specimen, and pathologic stage. No significant relationships were found between DNA ploidy and age, mean PAP value, and absolute PAP value. Of the 112 patients, 65 (58.0%) had disease limited to the prostate (pathologic Stages A and B); 47 (42.0%) had extraprostatic disease (pathologic Stages C and D1). The stage was related to the Gleason score (P less than 0.0001) where extraprostatic disease was associated with a Gleason score of 6 to 10. Nineteen (17.0%) patients had aneuploid tumors, and 93 (83.0%) had diploid tumors. DNA ploidy significantly correlated with pathologic stage (P = 0.04); aneuploidy was identified more frequently in patients with Stages C and D1 tumors. Aneuploid tumors occurred more frequently than diploid tumors in patients with a Gleason score of 6 to 10 (P = 0.034). Mean PSA values were higher in patients with aneuploid tumors (P = 0.078), extraprostatic neoplasms (P = 0.00001), and cancers with a Gleason score of 6 to 10 (P = 0.0004). Furthermore, PSA values greater than 10.0 ng/ml were associated with extraprostatic disease and a Gleason score of 6 to 10 (P less than 0.05 and P less than 0.001, respectively). Significant racial differences were found with respect to DNA ploidy, mean DNA indices, and mean PSA values. The 18 black patients had more DNA aneuploid tumors (P = 0.043), a higher mean DNA index (P = 0.017), and a higher mean PSA value (P = 0.043) than the 94 white patients. Both PSA and DNA ploidy analysis by flow cytometry appear to be valuable indicators in the evaluation of patients with prostatic carcinoma.

Topics: Acid Phosphatase; Aged; Aneuploidy; Antigens, Neoplasm; Biomarkers, Tumor; Black People; Diploidy; DNA, Neoplasm; Flow Cytometry; Humans; Male; Middle Aged; Neoplasm Staging; Ploidies; Prognosis; Prostate; Prostate-Specific Antigen; Prostatectomy; Prostatic Neoplasms; White People

PSA is a 34-kd 240-amino acid glycoprotein produced by the prostatic epithelial cells. It is a member of the glandular kallikrein gene family and has a high sequence homology with human glandular kallikrein (hGK-1). PSA is a serine protease and has chymotrypsin-, trypsin-, and esterase-like activities. It is secreted into the seminal fluid where it degrades two seminal vesicle proteins that are important components of the semen coagulum, thus playing an important role in semen liquefaction. The production of PSA protein appears to be under the control of circulating androgens acting through the androgen receptor. Therefore, the significance of a low serum PSA value in a patient who has undergone previous antiandrogen therapy may not be the same as that for a patient who has not received endocrine treatment.

Topics: Acid Phosphatase; Adenocarcinoma; Antigens, Neoplasm; Biomarkers, Tumor; Humans; Male; Molecular Structure; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms

Markers of human prostatic cancer are important diagnostic aids in the management of this most common tumor among US men. A rapidly expanding body of basic and clinical knowledge about the properties and behavior of these unique organ-specific macromolecules bridges the gap between sophisticated immunochemistry and everyday practice. As a consequence, the patient benefits, because greater opportunities for early detection of prostatic cancer provide more freedom in selecting the most effective treatment modalities. Parallel improvement in quantitative assessment of an existing tumor mass allows earlier and more precise monitoring of the positive therapeutic responses and/or disease progression, as well as better overall prognosis. In addition, marker molecules can provide specific targets for antibody-directed therapeutic compounds active against prostatic cancer. This study focused on three such markers: prostatic acid phosphatase, prostate-specific antigen, and a new membrane-associated marker defined by a monoclonal antibody called 7E11-C5. A critical evaluation of clinical usefulness and prospects for future developments are presented.

Topics: Acid Phosphatase; Antibodies, Monoclonal; Antigens, Neoplasm; Biomarkers, Tumor; Humans; Male; Prostate-Specific Antigen; Prostatic Neoplasms

Prostatic cancer was the first malignancy in which tumor markers could be used to follow the response to therapy or progression of the prostate cancer. The use of these tumor markers has been of significant clinical value in diagnosis and follow-up of patients. Over the years, significant technical improvements have been made on the sensitivity and specificity of the assays for prostatic acid phosphatase.

Topics: Acid Phosphatase; Biomarkers, Tumor; Humans; Male; Prognosis; Prostatic Neoplasms

The proposition of whether to adopt a system of mass screening for carcinoma of the prostate in the U.S. is well suited to the clinical decision analysis approach. The authors demonstrate this by using available data, which suggest that offering a screening program to all men ages 50 to 70 would be prohibitively expensive. The method also permits calculation of the eventual morbidity of screening and its costs. This analysis demonstrates the importance of attempting to predict ultimate patient outcomes before implementing any health care strategy as standard.

Topics: Acid Phosphatase; Aged; Aged, 80 and over; Antigens, Neoplasm; Biomarkers, Tumor; Decision Support Techniques; Humans; Male; Middle Aged; Palpation; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Sensitivity and Specificity

Acid phosphatase and prostate-specific antigen are extremely useful markers for the management of patients with prostatic carcinoma. Prostatic acid phosphatase, because of its relatively low sensitivity and specificity, as well as analyte instability and diurnal variability, is unsuitable for prostate cancer screening. Improved performance characteristics, stability, the lesser diurnal variation, and the association of elevated prostate-specific antigen with prostatic intraepithelial neoplasia make prostate-specific antigen possibly a better candidate for early detection of this common malignancy. Further investigations in this area are clearly indicated before we can recommend screening with prostate-specific antigen.

Topics: Acid Phosphatase; Antigens, Neoplasm; Biomarkers, Tumor; Humans; Male; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Specimen Handling

There are several areas of concern in dealing with clinical stage B disease. First, understaging is common. Second, recognition of extension into the seminal vesicles is important. Third, the patient's predicted life expectancy must be taken into account. Moreover, even clinically localized prostate cancer may have metastasized, and the need for surgical staging by lymph node dissection has been a significant factor in the authors' preference for radical retropubic rather than radical perineal prostatectomy. Neither of the two serum markers in clinical use is an absolute predictor of stage. Analysis of tumor ploidy may prove useful, and transrectal ultrasound warrants further study. In the elderly patient, the urologist certainly may elect to monitor the tumor without definitely deciding on operative versus conservative treatment.

Topics: Acid Phosphatase; Antigens, Neoplasm; Biomarkers, Tumor; Humans; Lymphatic Metastasis; Male; Pelvis; Prostate; Prostate-Specific Antigen; Prostatectomy; Prostatic Neoplasms

Topics: Acid Phosphatase; Antigens, Neoplasm; Biomarkers, Tumor; Humans; Male; Monitoring, Physiologic; Neoplasm Staging; Predictive Value of Tests; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms

Immunodiagnosis of prostate cancer is at a more advanced stage than that of most other tumors. Two well-known markers, prostatic acid phosphatase and prostate-specific antigen, have been used in the clinical management of patients. Prostate-specific antigen is a more sensitive and reliable marker than prostatic acid phosphatase. Serum prostate-specific antigen is effective in monitoring disease status, predicting recurrence, and detecting residual disease. Prostate-specific antigen is a tool for the histological differential diagnosis of metastatic carcinomas, especially in the identification of metastatic prostate tumor cells in distant organs and in the differentiation of primary prostate carcinoma from poorly differentiated transitional cell carcinoma of the bladder. Few data on biological function are available. Prostatic acid phosphatase functions as a phosphotyrosyl-protein phosphatase and prostate-specific antigen as a protease. Physiological function in the prostate remains to be elucidated. Several of the prostate-specific and prostate-tumor-associated antigens, as well as a putative prostate tumor-specific antigen, as recognized by monoclonal antibodies are available. Clinical evaluation of these potential markers is not yet available.

Topics: Acid Phosphatase; Adenocarcinoma; Antibodies, Monoclonal; Antigens, Neoplasm; Biomarkers, Tumor; Diagnosis, Differential; Enzyme-Linked Immunosorbent Assay; Humans; Immunologic Tests; Male; Neoplasm Metastasis; Neoplasm Proteins; Neoplasm Staging; Prostate-Specific Antigen; Prostatic Neoplasms; Reagent Kits, Diagnostic; Serum Globulins; Urinary Bladder Neoplasms

Prostatic acid phosphatase (PAP), prostate-specific antigen (PSA; or gamma-seminoprotein), and beta-microseminoprotein (beta-MSP; PSP94 or beta-inhibin) are the three predominant proteins secreted by the normal human prostate gland. In the epithelium of normal and hyperplastic prostatic acini and ducts PAP, PSA and beta-MSP have an identical immunohistochemical localization. Highly differentiated (grade I) carcinomas contain an almost equal number of PAP-, PSA- and beta-MSP-immunoreactive cells; the incidence of these cells is lower and they display a greater staining variability in the moderately and poorly (grade II-III) differentiated tumours. Especially in poorly differentiated tumours PSA seems to be a more sensitive immunohistochemical marker than PAP or prostatic carcinomas. Moreover, the use of PAP as a marker for prostatic carcinomas is complicated by the reported structural similarities between the prostatic secreted acid phosphatase and lysosomal acid phosphatase occurring in all tissues. The use of beta-MSP as a marker for prostatic carcinomas may be limited by indications of non-prostatic production of this protein.

Topics: Acid Phosphatase; Antigens, Neoplasm; Biomarkers, Tumor; Humans; Immunohistochemistry; Male; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Prostatic Secretory Proteins; Proteins; Seminal Plasma Proteins

A large number of cases of prostatic carcinoma are discovered unexpectedly by simple prostatectomy performed for presumed benign disease. The ability to discover these cancers preoperatively is an appealing concept, in other words, to screen: the use of a test to detect a disease in an asymptomatic individual. The ideal screening test would be noninvasive, inexpensive, reliable, and reproducible. It would also have a high sensitivity and specificity, neither allowing a disease process to be missed by a falsely negative result nor leading to unnecessary and more invasive studies by a falsely positive one. It has been suggested that an acceptable screening test have a sensitivity of at least 95 per cent and a specificity of 100 per cent. An equally important criterion for a successful screening program for cancer has to do with the biologic potential of the discovered malignancy. The adage is that more men die with prostate cancer than of prostate cancer. However, the biologic potential of prostate cancer has not been fully elucidated, and it is not entirely clear who will benefit from treatment and who should be left alone. At the present time, noninvasive imaging modalities and biochemical markers are not clinically useful in detecting occult prostatic carcinoma. Furthermore, no study has proved that routine screening reduces the mortality rate from prostate cancer. Many authors believe that screening men for prostate cancer should be regarded as investigational and that currently, only screening programs for breast and cervical cancer have been fully demonstrated to be effective. New studies are needed that include control groups who are not subjected to the early diagnostic modality, assessing both the disadvantages of the screening program and the potential benefits.

Topics: Acid Phosphatase; Animals; Biomarkers, Tumor; Humans; Male; Prostatic Neoplasms; Ultrasonography

Topics: Acid Phosphatase; Alkaline Phosphatase; Biomarkers, Tumor; Clinical Trials as Topic; Humans; Male; Prognosis; Prostatic Neoplasms; Statistics as Topic; Time Factors

In 1979, Wang and associates isolated prostate-specific antigen (PSA). Only recently, however, has the clinical importance of this new tumor marker been recognized. It is now widely accepted that PSA represents a significantly more effective tumor marker than prostatic acid phosphatase (PAP). This article will review the chemistry associated with PSA, the application of PSA in immunohistochemistry, salient features of the two clinically available assays, factors that affect the circulating level of PSA, and the usefulness of PSA in the staging, monitoring, and screening of patients with prostatic carcinoma.

Topics: Acid Phosphatase; Antigens, Neoplasm; Biomarkers, Tumor; Humans; Male; Prostate-Specific Antigen; Prostatic Hyperplasia; Prostatic Neoplasms; Reference Values

Topics: Acid Phosphatase; Antigens, Neoplasm; Biomarkers, Tumor; Humans; Male; Predictive Value of Tests; Prostate-Specific Antigen; Prostatic Neoplasms; Rectum; Ultrasonography

The diagnosis of prostatic cancer is usually made when the disease is no longer curable and it is important to find other means to discover the cancer at its earliest stage. Tumour markers, such as prostatic specific antigen, may enable this.

Topics: Acid Phosphatase; Antigens, Neoplasm; Biomarkers, Tumor; Humans; Male; Prostate-Specific Antigen; Prostatic Neoplasms

Bilateral breast mass was found in a 71-year-old male who had been placed on estrogen therapy for stage D2 prostatic adenocarcinoma. Microscopically the mass contained adenocarcinoma morphologically similar to that of the prostate, but the differential diagnosis was impossible between metastatic prostatic carcinoma and primary breast carcinoma. Formalin-paraffin sections of both tumors were stained positively by PSA (prostatic specific antigen) and PAP (prostatic acid phosphatase) using B-SA (biotin-streptavidin) system technique and prostatic origin of the breast mass was confirmed. Prostatic origin for metastatic carcinoma in the breast is are with only 30 reported cases in the literature including 5 Japanese cases. In most of them the diagnosis of the breast lesion as prostatic carcinoma has been made on morphologic and clinical grounds only. Accurate diagnosis is important for the prognosis of the patient, and immunohistochemical method is useful for he diagnosis of breast carcinoma metastasized from prostatic origin.

Topics: Acid Phosphatase; Adenocarcinoma; Aged; Antigens, Neoplasm; Breast Neoplasms; Diagnosis, Differential; Estrogens; Humans; Immunohistochemistry; Male; Prostate-Specific Antigen; Prostatic Neoplasms

The determination of gamma-seminoprotein (gamma-Sm) (also called prostate-specific antigen [PSA], prostate antigen [PA], or p30) in human serum has been recently demonstrated to be more sensitive and specific for diagnosing prostate cancer and monitoring the condition of patients with prostate cancer than the prostatic acid phosphatase (PAP) test. Because the gamma-Sm (PSA) test seems likely to replace the PAP test in the area of urology and study of prostate-specific antigens is expanding, we have reviewed physicochemical properties and clinical significance of two prostate-specific antigens, gamma-Sm (PSA) and beta-microseminoprotein (beta-MSP). Both proteins have been proved to originate in the prostate gland and have not been detected in any other human tissues by an immunohistologic study. The usefulness of gamma-Sm and beta-MSP in determining the origin of metastatic tumors has also been shown. gamma-Sm is a glycoprotein with a molecular weight of 26,079 for the peptide portion, of which the amino acid sequence is identical to so-called PSA and homologous with serine proteases (the kallikrein family). Its chymotrypsin-like activity with a unique substrate specificity has also been demonstrated. The molecular weight of beta-MSP is 10,652 from the amino acid sequence, in which the protein has been shown to contain no alanine residue.

Topics: Acid Phosphatase; Biomarkers, Tumor; Humans; Immunohistochemistry; Male; Prognosis; Prostate; Prostatic Neoplasms; Prostatic Secretory Proteins; Proteins; Seminal Plasma Proteins

Topics: Acid Phosphatase; Biomarkers, Tumor; Humans; Male; Neoplasm Staging; Prostatic Neoplasms; Ultrasonography

Topics: Acid Phosphatase; Female; Humans; Male; Prostatic Neoplasms; Reference Values

The development of hybridoma technology has increased research efforts and clinical applications in the area of radioimmunodetection. Despite the many investigative antibodies directed against prostatic tissue or prostate cancer cell lines, only two have been tested in clinical trials. A 111In-labeled antibody directed against prostate-specific antigen, the best available serum tumor marker for prostate cancer, has shown poor sensitivity in limited clinical radioimmunoimaging trials. Monoclonal antibodies against prostatic acid phosphatase have shown better imaging results, particularly at higher antibody doses (greater than or equal to 40 mg). The limitations of this antibody include the poor results in detecting soft tissue lesions, including the primary lesion; the development of human antimouse antibodies in 50% of the patients at doses greater than or equal to 40 mg; the expense of the antibody; and the fact that better results are currently attainable by other less expensive imaging modalities. If and when a more suitable antibody or fragment is developed, the prospect of improved staging and new treatments using immunologic conjugates carrying therapeutic agents may become realities. Until such time, prostatic cancer will be staged with other currently available imaging modalities and conventional therapies with their limitations will remain state of the art.

Topics: Acid Phosphatase; Antibodies, Monoclonal; Humans; Male; Prostate; Prostatic Neoplasms; Radioisotopes; Radionuclide Imaging

Immunological techniques have enabled us to see that mammalian sperm undergo complex surface changes during maturation in the male reproductive tract. Binding affinity and sperm surface binding domains have been demonstrated using immunocytochemical technique. Recent studies using monoclonal antibodies suggest that these highly specific probes are useful for detecting changes in the sperm surface during epididymal transit and in defining the role of these complex changes in sperm maturation and the process of fertilization. Studies involving immunological mapping of the sperm surface, in parallel with immunohistological and functional inhibition test, have provided important information concerning the role of individual sperm antigens in fertility. A better understanding of local antibody production and cell-mediated immune responses in the male reproductive tract has also led to the understanding of immunological infertility. Sperm membrane is comprised of multiple domains each of which is sharply demarcated, with a unique composition and physiological role.

Topics: Acid Phosphatase; Animals; Autoantigens; Epididymis; Fertility; Genitalia, Male; Humans; Immunohistochemistry; Infertility, Male; Male; Prostate; Prostatic Neoplasms; Sperm Maturation; Spermatozoa; Testis

PSA and PAP are effective immunohistologic markers for prostatic cancer metastases. PSA seems to be more sensitive than PAP for diagnosing metastatic prostatic cancer. Simultaneous determination of PSA and PAP yields an additive clinical value in diagnosing and follow-up of prostatic cancer. The prognostic reliability for disease progression (recurrence and treatment response) seems to be PSA greater than PAP greater than AcidP greater than Alkal. P.

Topics: Acid Phosphatase; Alkaline Phosphatase; Antigens, Neoplasm; Biomarkers, Tumor; Follow-Up Studies; Humans; Male; Neoplasm Metastasis; Prostate-Specific Antigen; Prostatic Neoplasms

Topics: Acid Phosphatase; Alkaline Phosphatase; Antigens, Neoplasm; Biomarkers, Tumor; Humans; Male; Prognosis; Prostate-Specific Antigen; Prostatic Neoplasms

During the four years between January, 1983 and December, 1986, transurethral resection of the prostatic gland (TUR-P) was performed on 108 patients with benign prostatic hypertrophy at Osaka Municipal Kita Citizen's Hospital. Histopathological examination of the transurethral resection specimens revealed 9 cases (8.3%) of incidental carcinoma. In this study, the average patient age, preoperative prostatic acid phosphatase (PAP) level and weight of resection specimens were compared for all 108 patients. For the 9 patients with incidental carcinoma, the clinical stage, histological grade and therapy were evaluated.

Topics: Acid Phosphatase; Aged; Humans; Male; Middle Aged; Prostatectomy; Prostatic Hyperplasia; Prostatic Neoplasms

Acid phosphatase is a secretory product frequently utilized as a tumor marker for disseminated, late stage (D2) prostatic cancer. In the 40 years since this association has been recognized, this enzyme has been subjected to extensive biochemical and immunological characterizations. These techniques have also been adapted for rapid and specific determinations of the prostatic isoenzyme levels using a variety of techniques. Since acid phosphatase levels do not become significantly elevated until late stage cancer, newer markers such as prostate-specific antigen have been sought which appear earlier and may be more useful for the screening and monitoring of high risk populations. At this time it is appropriate to review the current and future status of acid phosphatase as a diagnostic aid.

Topics: Acid Phosphatase; Antigens, Neoplasm; Biomarkers, Tumor; Humans; Male; Prognosis; Prostate-Specific Antigen; Prostatic Neoplasms; Radioimmunoassay

Topics: Acid Phosphatase; Antigens, Neoplasm; Biomarkers, Tumor; Bone and Bones; Creatine Kinase; Humans; Isoenzymes; Male; Neoplasm Staging; Polyamines; Prostate-Specific Antigen; Prostatic Neoplasms; Radiography

Topics: Acid Phosphatase; Antigens, Neoplasm; Biomarkers, Tumor; Blood Group Antigens; Glucuronidase; Histocytochemistry; Hormones; Humans; Male; Mucins; Neoplasm Staging; Prostate-Specific Antigen; Prostatic Neoplasms; Receptors, Cell Surface

Topics: Acid Phosphatase; Antigens, Neoplasm; Biomarkers, Tumor; Hormones; Humans; Male; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Receptors, Cell Surface

Topics: Acid Phosphatase; Adenocarcinoma; Humans; Immunoenzyme Techniques; Male; Neoplasm Staging; Prostate; Prostatic Neoplasms; Radioimmunoassay

Topics: Acid Phosphatase; DNA, Neoplasm; Flow Cytometry; Histocytochemistry; Humans; Light; Male; Prostatic Neoplasms; Scattering, Radiation

Prostate cancer is a leading cause of cancer mortality in adult men. The majority of patients have subclinical systemic disease at diagnosis and will eventually require systemic therapy for palliation of symptoms. Recent development of new hormonal treatment options (e.g., gonadotropin-releasing hormone analogues and estramustine) has yet to demonstrate potential for improving the therapeutic index or for lengthening survival over results achieved with traditional modalities (i.e., supplemental estrogens or castration). Chemotherapeutic agents have demonstrated palliative efficacy and are being tested in multidrug regimens and in combination with hormones. At the present time, the optimal use of cytotoxic drugs remains undefined, since recently published studies have shown neither that combination chemotherapy is superior to single agents nor that chemo-hormonal therapy produces more favorable results than hormonal treatment alone.

Topics: Acid Phosphatase; Androgens; Antineoplastic Agents; Bone Neoplasms; Cell Division; Diethylstilbestrol; Humans; Male; Orchiectomy; Prostatic Neoplasms; Testosterone

The clinical features of a new prostate tumor marker, prostate-specific antigen (prostate antigen, PA), has been reviewed. Although PA cannot be used in early detection of prostate cancer, simultaneous determination of PA and PAP yields an additive clinical value in immuno-diagnosis of prostate cancer. At the present stage of development, PA is most useful as a prognostic marker for monitoring disease recurrence and treatment response. Also, PA is an effective immunohistologic marker for differential diagnosis of metastatic carcinomas with unknown primary, especially in the identification of metastatic prostate tumor in distant metastases and in the differentiation of primary prostate carcinoma from poorly differentiated transitional cell carcinoma of the bladder. Unequivocal evidence is not yet available on the role of circulating PA-binding globulin as an auto-antibody or an anti-tumor antibody as a result of patient's immune response. This observation is of clinical value for investigation of prostate cancer biology. The intriguing protease activity as detected in PA may provide new avenues for prostate cancer research.

Topics: Acid Phosphatase; Antibodies, Monoclonal; Antigens; Enzyme-Linked Immunosorbent Assay; Humans; Male; Prostate-Specific Antigen; Prostatic Hyperplasia; Prostatic Neoplasms

Topics: Acid Phosphatase; alpha-Fetoproteins; Antigens, Neoplasm; Blood Group Antigens; Carcinoembryonic Antigen; Chorionic Gonadotropin; Chorionic Gonadotropin, beta Subunit, Human; Female; Humans; Immunoenzyme Techniques; Kidney Neoplasms; Male; N-Acetylneuraminic Acid; Peptide Fragments; Prostate-Specific Antigen; Prostatic Neoplasms; Receptors, Steroid; Sialic Acids; Testicular Neoplasms; Urinary Bladder Neoplasms; Urogenital Neoplasms

Topics: Acid Phosphatase; Antigens; Autoantibodies; Humans; Immunity, Cellular; Immunization; Isoantibodies; Male; Organ Specificity; Prostatic Hyperplasia; Prostatic Neoplasms

The methods are reviewed for obtaining monolayer epithelium cultures both in normal and hyperplastic or malignant prostate glands. Preparation of pure epithelial tissue cultures is dealt with in detail. The major prostate cell lines are described. Special attention is paid to the markers of differentiation and sensitivity to hormones in normal and tumour prostatic cells in vitro. Prospects for the use of prostatic cell cultures as models in oncology are outlined.

Topics: Acid Phosphatase; Adult; Androgens; Antigens; Cell Differentiation; Cell Line; Cell Transformation, Neoplastic; Cells, Cultured; Culture Media; Cytological Techniques; Epithelial Cells; Epithelium; Fibroblasts; Gene Expression Regulation; Humans; Infant, Newborn; Male; Middle Aged; Prostate; Prostatic Hyperplasia; Prostatic Neoplasms

Proteins secreted by dog prostate differ from those of other species and in particular from those of man, both in terms of quantity and quality. These differences can be observed in the electrophoretic pattern of proteins in polyacrylamide gels and in enzymes such as phosphatases, glycohydrolases and proteases. For instance, canine acid phosphatase, although quite similar biochemically to the human enzyme, is about one hundred fold less concentrated in both prostatic tissue and seminal plasma than in the human. By contrast, arginine esterase, which is virtually absent in human prostatic secretion, comprises more than 90% of total proteins secreted by dog prostate. The most recent data on each of these enzymes, enzyme classes and proteins will be reviewed. Despite recent advancement of knowledge on the biochemistry of these constituents, their biological function as well as their contribution to the pathogenesis of prostatic diseases still remain a matter of speculation. For both of these aspects, dog appears to be a particularly interesting model.

Topics: Acid Phosphatase; Amino Acid Sequence; Animals; Dogs; Electrophoresis, Polyacrylamide Gel; Glucosidases; Male; Peptide Hydrolases; Prostate; Prostatic Neoplasms; Proteins; Semen; Substrate Specificity

Topics: Acid Phosphatase; Adrenalectomy; Androgen Antagonists; Androgens; Antineoplastic Agents; Bone Neoplasms; Combined Modality Therapy; Drug Evaluation; Estrogens; Gonadotropin-Releasing Hormone; Humans; Male; Neoplasms, Hormone-Dependent; Orchiectomy; Prostatic Neoplasms

The authors review recent developments in the immunodiagnosis of prostatic cancer. Monoclonal antibodies to prostatic acid phosphatase, prostate-specific antigen, and several human prostate and prostate-cancer-related components are available. Prostatic acid phosphatase and prostatic antigen assays are still the only immunologic tools with clinical applications.

Topics: Acid Phosphatase; Antibodies, Monoclonal; Antigen-Antibody Complex; Antigens, Neoplasm; Counterimmunoelectrophoresis; Enzyme-Linked Immunosorbent Assay; Fluorescent Antibody Technique; Humans; Immunosorbent Techniques; Male; Neoplasm Proteins; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Radioimmunoassay

The status of the biochemical markers explored for use in patients with carcinoma of the prostate is reviewed. No unique marker has been identified. However, a variety of substances, primarily enzymes and specific proteins, found in the serum, urine, and prostatic fluid, have been evaluated. Their main value remains in the staging of disease and the monitoring of response to therapy.

Topics: Acid Phosphatase; Alkaline Phosphatase; alpha-Fetoproteins; Amino Acids; Antigens, Neoplasm; Body Fluids; Carcinoembryonic Antigen; Carcinoma; Cholesterol; Creatine Kinase; Fibronectins; Glucose-6-Phosphate Isomerase; Humans; Hydroxyproline; Isocitrate Dehydrogenase; Isoenzymes; L-Lactate Dehydrogenase; Male; Orosomucoid; Prostate-Specific Antigen; Prostatic Neoplasms; Ribonucleases; Spermidine

Topics: Acid Phosphatase; DNA, Neoplasm; Estramustine; Flow Cytometry; Gonadotropin-Releasing Hormone; Humans; Immunotherapy; Male; Methylation; Oncogenes; Prostatic Neoplasms

Topics: Acid Phosphatase; Antineoplastic Agents; Bromocriptine; Castration; Combined Modality Therapy; Cyproterone; Estramustine; Estrogens; Fluorouracil; Humans; Lisuride; Male; Neoplasm Metastasis; Prostatic Neoplasms; Random Allocation

Metastatic prostatic cancer can be present in a variety of different ways. The authors describe the differences among stages D-0, D-1, and D-2 disease and present the treatment options for each of the substages. They summarize and integrate the clinical evidence that bears on the potential efficacy of each treatment.

Topics: Acid Phosphatase; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Brachytherapy; Carcinoma; Castration; Clinical Trials as Topic; Combined Modality Therapy; Diethylstilbestrol; Estrogens; Gonadotropin-Releasing Hormone; Hormones; Humans; Leuprolide; Lymph Node Excision; Lymphatic Metastasis; Male; Neoplasm Staging; Prostatectomy; Prostatic Neoplasms; Radioisotope Teletherapy

At the close of each decade, we are reminded by medical statisticians that our longevity increases significantly. For the male, especially if he be of black race this statement has an ironic twist. Over age 70, prostatic "cancer" assumes the leadership list of "cancers" in general, supplanting lung and colo-rectal. One interesting point evolved by careful autopsy studies suggests that this incidence is found coincidentally and is not primarily responsible for the cause of death. This illustrates a different significance to other neoplasia, and offers useful opportunities to study the evolution of a neoplasm. In contrast to other "cancers" (for example pulmonary), the histological nature of the tumor is almost totally derived from the acinar lobules and designated adenocarcinoma. Neoplasia arising from the fibromuscular stroma (sarcoma) and metaplastic ductus (squamous cell carcinoma) constitute less than 1% of all prostate cancers. Histological appearances, however, are not as simple as hoped. As in many tumors the section may present a uniform well-differentiated adenocarcinoma in which the acinar structure is well maintained--yet at the opposing end of the spectrum show a fatally dedifferentiated picture whose organ origin is difficult to determine. Adding to the complication is the wide variation, far more commonly seen, of the mixed tumor with all variations presenting a composite panorama of histology. Indeed the pure type is rare. As with all neoplastic disease, early detection is critical, since opportunity for cure with the various forms of therapy from surgery through radiation to chemotherapy are increasing rapidly. The prostate gland is relatively accessible to the trained finger of the physician and later stages of the disease are palpable. However, the earliest Stage (I) is not discovered by rectal examination, hence provides an ideal opportunity for the serum tumor marker, to identify disease. Since 1938, disseminated prostatic adenocarcinoma has been associated with elevation of activity of an enzyme acid phosphatase. Although there are several isoenzymes the prostatic specific one has in the past been assayed by different spectrophotometric techniques using selective substrate and chemical inhibition. More recently various immunological methods have added a greater sensitivity and specificity to the early detection of prostatic adenocarcinoma. However is should be clearly stated that prostatic acid phosphatase is not cancer specific and ca

Topics: Acid Phosphatase; Adenocarcinoma; Alkaline Phosphatase; Antigens, Neoplasm; Bone Marrow; Carcinoembryonic Antigen; Creatine Kinase; Enzyme-Linked Immunosorbent Assay; gamma-Glutamyltransferase; Humans; L-Lactate Dehydrogenase; Male; Prostate; Prostatic Neoplasms; Radioimmunoassay; Ribonucleases

Topics: Acid Phosphatase; Alkaline Phosphatase; Antigens, Neoplasm; Bone Marrow; Carcinoembryonic Antigen; Creatine Kinase; Enzyme-Linked Immunosorbent Assay; Epoprostenol; Humans; Immunoenzyme Techniques; Isoenzymes; L-Lactate Dehydrogenase; Male; Polyamines; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Radioimmunoassay

Topics: Acid Phosphatase; Adenocarcinoma; Bone and Bones; Bone Neoplasms; Humans; Kidney Neoplasms; Male; Prognosis; Prostate; Prostatic Neoplasms; Radionuclide Imaging; Testicular Neoplasms; Urinary Bladder Neoplasms

Topics: Acid Phosphatase; Antineoplastic Agents; Bone Neoplasms; Carcinoembryonic Antigen; Cisplatin; Clinical Trials as Topic; Creatine Kinase; Doxorubicin; Humans; Male; Prostatic Neoplasms

Following the studies of Huggins and colleagues in 1941, the hormonal treatment of prostatic cancer has been aimed at neutralizing the influence of testicular androgens through surgical castration or the administration of high doses of estrogens. These two approaches cause a temporary improvement in 60 to 70% of advanced prostatic cancer. However, castration is not always well accepted and high doses of estrogens are frequently accompanied by lethal cardiovascular side effects. Following our observation that treatment with LHRH agonists causes a blockage in the biosynthesis of testosterone by the testis accompanied by a marked reduction in prostatic weight in the rat, the possibility was opened for a new approach in the treatment of prostatic cancer. Fortunately, among all species studied, man is the most sensitive to the inhibitory effect of LHRH agonists on testicular androgen biosynthesis and near-medical castration can be easily achieved without secondary effects other than those related to low androgen levels. Following long-term studies in the rat which have shown that the inhibitory effect of LHRH agonists is markedly potentiated by simultaneous administration of a pure antiandrogen, a study using the LHRH agonist [D-Ser(TBU)6, des-Gly-NH2(10)] LHRH ethylamide (HOE-766) and the pure antiandrogen RU-23908 was performed in men with advanced prostatic cancer. The combined treatment with the LHRH agonist and the antiandrogen in 37 patients not previously treated caused a positive objective response in 97% of cases while, previously, partial hormonal treatment achieved through castration or high doses of estrogens caused a positive response in 60 to 70% of patients. The serum levels of prostatic acid phosphatase (PAP) were decreased to 40% of control as early as four days after starting combined hormonal therapy. By contrast, in patients previously treated with estrogens or castrated, complete neutralization of adrenal androgens by the antiandrogen led to a much lower rate of positive response ranging from 25 to 55%. In patients previously treated, there is thus a predominance of tumor cells insensitive to androgens. An additional important finding in this study is that the administration of the antiandrogen prevents the flare-up of the disease frequently observed when LHRH agonists are administered alone.(ABSTRACT TRUNCATED AT 400 WORDS)

Topics: Acid Phosphatase; Androgen Antagonists; Buserelin; Drug Synergism; Drug Therapy, Combination; Gonadotropin-Releasing Hormone; Hormones; Humans; Imidazoles; Imidazolidines; Male; Prostate; Prostatic Neoplasms

Topics: Acid Phosphatase; Aged; Electrophoresis, Polyacrylamide Gel; Humans; Male; Prostatic Neoplasms

Topics: Acid Phosphatase; Biopsy; Biopsy, Needle; Bone Neoplasms; Clinical Enzyme Tests; Cytodiagnosis; Humans; Male; Mass Screening; Methods; Palpation; Prostatic Neoplasms; Radiography

Topics: Acid Phosphatase; Castration; Estrogens; Humans; Male; Minnesota; Prostate; Prostatic Neoplasms

Topics: Acid Phosphatase; Aged; Androgens; Humans; Male; Polyamines; Prostatic Hyperplasia; Prostatic Neoplasms; Receptors, Androgen; Receptors, Steroid; Spermidine; Spermine; Testosterone

Topics: Acid Phosphatase; Alkaline Phosphatase; Humans; Immunoenzyme Techniques; Isoenzymes; Male; Prostatic Neoplasms; Radioimmunoassay

Topics: Acid Phosphatase; Biopsy, Needle; Complement C3; Complement C4; Histological Techniques; Humans; Isoenzymes; L-Lactate Dehydrogenase; Male; Prostatic Neoplasms; Tomography, X-Ray Computed; Transferrin; Ultrasonography

Evaluation of lymph node involvement in carcinoma of the prostate is an essential step in staging when radical management is still possible. For this purpose, lymphography, lymphoscintigraphy, thin-needle transcutaneous lymph node biopsy, and pelvic lymphadenectomy have been variously combined since 1978 in 20 new cases (T1-T2-T3/Mo). Pedal lymphography displayed a good correlation with the histological data offered by adenectomy, and proved indispensable for the execution of transcutaneous biopsy under fluoroscopic control. Pedal lymphoscintigraphy is less invasive than lymphography. It provided suggestive morphological pictures of the lymph node chains, including those outside the pelvis; these, however, were difficult to interpret and must be regarded as of great, but complementary utility. Intraprostatic lymphoscintigraphy by injecting the radionuclide into the gland capsule permitted visualisation of the periprostatic nodes and confirmed previous experimental and clinical data. Lymph node metastases were seen in 50% of cases. Their frequency was inversely proportional to the degree of histological differentiation. In all cases, the external iliac and "obturator" (internal chain of external iliac group) notes were involved. Voluminous metastases were observed in two cases of "incidental" (To) carcinoma. The lymphography contrast medium was always found in the "obturators". It is suggested that these findings underscore the need for careful lymph node examination, even in the earliest stages of prostate cancer. They also raise further queries with regard to the treatment of incidental carcinoma.

Topics: Acid Phosphatase; Aged; Alkaline Phosphatase; Biopsy, Needle; Bone and Bones; Humans; Liver; Lymph Nodes; Lymphatic Metastasis; Lymphography; Male; Middle Aged; Neoplasm Invasiveness; Neoplasm Staging; Prostatic Neoplasms; Radionuclide Imaging

Topics: Acid Phosphatase; Clinical Enzyme Tests; Creatine Kinase; Evaluation Studies as Topic; Isoenzymes; Male; Methods; Prostate; Prostatic Neoplasms; Radioimmunoassay

We have reviewed several tumor markers that our advocates feel are now clinically useful, involve current assay technology, and are based on already available information. These include, in selected instances, estrogen receptors for breast cancer, thyrocalcitonin for medullary cancer of the thyroid, prostatic acid phosphatase for cancer of the prostate, alpha-fetoprotein for hepatocellular cancer, and carcinoembryonic antigen for monitoring colon cancer. We have considered the potential use of measurement of serum proteases and protein degradation products due to their activity as possible future areas of development, and we have explored measurement of tissue aryl hydrocarbon hydroxylase to identify populations at risk of cancer resulting from chemical carcinogenesis. It is clear that the study of tumor markers is already improving patient care in some specific areas and offers exciting potential for the future.

Topics: Acid Phosphatase; Animals; Antigens, Neoplasm; Aryl Hydrocarbon Hydroxylases; Blood Proteins; Breast Neoplasms; Calcitonin; Clinical Enzyme Tests; Clinical Laboratory Techniques; Female; Humans; Male; Neoplasms; Neoplasms, Experimental; Prostate; Prostatic Neoplasms; Rats; Receptors, Estrogen; Receptors, Progesterone; Thyroid Neoplasms

Topics: Acid Phosphatase; Antigens, Neoplasm; Cell Division; Chromosome Aberrations; Dihydrotestosterone; Humans; Hybridomas; Karyotyping; Male; Neoplasm Staging; Prostate; Prostatic Neoplasms; Testosterone

Topics: Acid Phosphatase; Adrenal Gland Neoplasms; alpha-Fetoproteins; Antigens, Neoplasm; Chorionic Gonadotropin; Chromosome Aberrations; Diagnostic Errors; Female; Humans; Immunochemistry; Immunoenzyme Techniques; Kidney Neoplasms; L-Lactate Dehydrogenase; Male; Neoplasms, Glandular and Epithelial; Pregnancy-Specific beta 1-Glycoproteins; Prostatic Neoplasms; Radioimmunoassay; Receptors, Cell Surface; Testicular Neoplasms; Urinary Bladder Neoplasms; Urologic Neoplasms

Topics: Acid Phosphatase; Alkaline Phosphatase; alpha-Fetoproteins; Antigens, Neoplasm; Carcinoembryonic Antigen; Fructose-Bisphosphate Aldolase; Humans; Isoenzymes; L-Lactate Dehydrogenase; Lymphokines; Lymphoma; Male; Neoplasm Metastasis; Neoplasms; Paraneoplastic Syndromes; Prostatic Neoplasms

Limited evidence suggests that prostatic cancer cells express antigens that are immunogenic in the host. Some of these tumor-associated antigens are fetal antigens and others may be oncogenic viral-induced tumor antigens. In addition, both benign and malignant prostatic epithelial cells produce an antigenically distinctive form of acid phosphatase, but it is unknown whether acid phosphatase can function as a target for cytotoxic mechanisms. There is ample evidence that host cell-mediated immunologic activity is depressed in many prostatic cancer patients. The mechanisms underlying these impairments are unclear, but a number of factors has been implicated including uncharacterized "serum blockers," alpha-2 globulins, and circulating antigen-antibody complexes. Endocrine manipulations can also alter host immune mechanisms. There is some evidence to suggest that host immune competence correlates inversely with tumor progression in patients who have relapsed after endocrine therapy. Immunotherapy for prostatic cancer has not been adequately studied. There have been a few inconclusive attempts at active immunotherapy using bacille Calmette Guérin and cryosurgery and virtually no attempts at passive immunotherapy. The future prospects for immunology as a useful tool in the management of prostatic cancer patients are discussed.

Topics: Acid Phosphatase; Animals; Antigens, Neoplasm; Carcinoembryonic Antigen; Dinitrochlorobenzene; Humans; Immunotherapy; Killer Cells, Natural; Lymphocyte Activation; Male; Neoplasms, Experimental; Prostatic Neoplasms; Rats; T-Lymphocytes

A number of chemotherapeutic agents show moderate promise for the palliative treatment of metastatic prostatic carcinoma. Although patterns of metastatic disease make classic response rates difficult to obtain and interpret, doxorubicin, cyclophosphamide, dacarbazine (DTIC), and cisplatin have activity in patients who have failed conventional hormonal treatment. In most studies, a survival advantage is seen for responders to these and other chemotherapeutic agents, but no survival advantage has been seen for the treatment cohorts when compared to groups not receiving chemotherapy. Therefore, estimates of the usefulness of these agents must be considered tentative. Multiple drug therapy has not yet shown definite superiority to single agent treatment. The uses and limitations of acid phosphatase as a tumor marker, as well as particular difficulties in measuring tumor response in the disease, are detailed herein.

Topics: Acid Phosphatase; Adenocarcinoma; Antineoplastic Agents; Cisplatin; Clinical Trials as Topic; Cyclophosphamide; Doxorubicin; Drug Therapy, Combination; Estramustine; Fluorouracil; Humans; Lomustine; Male; Prednimustine; Prostatic Neoplasms

Topics: Acid Phosphatase; Adenocarcinoma; Aged; Bone Neoplasms; Humans; Lymphatic Metastasis; Male; Neoplasm Staging; Prostatic Neoplasms

This paper reports a case of carcinoma of the prostate in an 11-year-old boy. The clinical findings were characterized by a mass in the prostatic region, extensive osteoblastic bone metastasis, and normal serum acid phosphatase. Autopsy demonstrated an undifferentiated tumor, which probably originated from the outer gland of the prostate. Metastases to the bones, liver, lungs, and the lymph nodes were present. Light and electron microscopic studies revealed undifferentiated neoplastic cell, which is in contrast to the usual adenocarcinoma in older individuals. Histochemical examination failed to demonstrate acid phosphatase activity within the tumor cells. The authors considered that this tumor probably originated from immature basal cells of the prostatic gland. Review of the literature disclosed 15 cases of carcinoma of the prostate in individuals under 21 years of age. These cases were also characterized by an undifferentiated appearance of tumor cells and normal serum acid phosphatase level.

Topics: Acid Phosphatase; Adolescent; Adult; Bone Neoplasms; Carcinoma; Child; Child, Preschool; Humans; Infant; Male; Neoplasm Metastasis; Prostatic Neoplasms

Topics: Acid Phosphatase; Blood Group Antigens; Carcinoembryonic Antigen; Female; Gastrointestinal Hormones; Humans; Immunoenzyme Techniques; Leukemia; Lymphoma; Male; Neoplasms; Ovarian Neoplasms; Pituitary Hormones; Pregnancy Proteins; Prostatic Neoplasms; Teratoma; Testicular Neoplasms; Thyroid Neoplasms

Carcinoma of the prostate is the second most common cancer in men, yet no significant change in overall survival has occurred since the original description of the results of castration by Huggins and Hodges. Many important questions about the disease remain unanswered. The cause of prostatic cancer is unknown, and few specific environmental or viral agents have been linked with the tumor. Increased recognition of the importance of frequent digitial rectal examination has resulted in more tumors being diagnosed in early stages. Developments in sonography suggest that it may be useful in detecting the presence of prostatic cancer and whether extraprostatic extension has occurred. Recent inprovements in the sensitivity of prostatic acid phosphatase assays have been made, but their use as a screening tool remains limited. In patients with clinical stage B lesions that are microscopically confined to the prostate, treatment by radical prostatectomy appears to confer greatest survival. The exact role of radiotherapy remains to be defined. However, when the tumor extends beyond the prostate and is localized to the pelvis, external beam ro interstitial radiation is appropriate. Pelvic lymphadenectomy has significant morbidity, but less invasive methods of pelvic nodal evaluation are less accurate. Lymphadenectomy has not been shown to have any therapeutic effect. Whether hormonal therapy improves survival needs further investigation, and efforts must continue to develop means of predicting hormonal responsiveness. Those patients unlikely to respond to hormonal therapy should be treated with early chemotherapy.

Topics: Acid Phosphatase; Antineoplastic Agents; Drug Therapy, Combination; Global Health; Humans; Lymphatic Metastasis; Male; Neoplasm Metastasis; Prostatectomy; Prostatic Neoplasms

Topics: Acid Phosphatase; Cobalt Radioisotopes; Estrogens; Humans; Lymphatic Metastasis; Lymphography; Male; Neoplasm Metastasis; Neoplasm Staging; Physical Examination; Prostatectomy; Prostatic Neoplasms; Radiotherapy, High-Energy

Acid phosphatase is a ubiquitous lysosomal enzyme that hydrolyses organic phosphates at an acid pH. Although the postpuberteral prostatic epithelial cell contains a uniquely high concentration of acid phosphatase, cellular components of bone, spleen, kidney, liver, intestine, and blood also contain this enzyme. The discovery that prostatic carcinoma cells often retain a high concentration of acid phosphatase characteristic of the normal postpubertal gland led to the recognition of the first clinically useful tumor marker. Recognition that the serum of patients with prostatic malignancy frequently contains an increased concentration of this enzyme has resulted in persistent efforts to identify the source, to accurately quantitate the level of serum acid phosphatase, and to determine the clinical significance of those levels. A variety of enzymatic and immunologic techniques have been employed to measure acid phosphatase. In the past, various substrates and inhibitors were utilized to increase specificity and sensitivity. Emphasis has now shifted to the development of radioimmunoassay and counterimmunoelectrophoresis in an attempt to enhance those parameters. Judgment of their efficacy awaits further testing and evaluation. The clinical significance of normal and abnormal serum acid phosphatase is constantly being reevaluated. In order to maximize the value of laboratory measurements, the clinical and pathologic status of the patient, the techniques employed in obtaining and storing the blood sample and the procedures used in analysis must be known and considered. Traditionally, the serum prostatic acid phosphatase has been thought to originate in the prostatic cancer cell and has been used to stage the disease. Until recently, elevated serum values have been accepted as an indication of extraprostatic disease, and were thought to rule out lesions confined to the prostate. The elevation of acid phosphatase levels in patients with disseminated disease or the failure of elevated levels to return to normal with treatment have been assumed to indicate a poor prognosis. However, unequivocal documentation of the validity of these statements is not available. Newer immunologic techniques for measuring acid phosphatase may significantly alter our current concept of its role as a tumor marker.

Topics: Acid Phosphatase; Bone Marrow; Clinical Enzyme Tests; Counterimmunoelectrophoresis; Humans; Male; Prostatic Diseases; Prostatic Neoplasms; Radioimmunoassay

The most reliable laboratory test for prostate cancer remains prostatic phosphatase determination. With the spectrophotometric method, however, falsely negative results are to be expected in 40% of stage D lesions. In only one third of patients with localized disease results are correctly positive. This poor specificity and sensitivity can be improved by radioimmunoassay (RIA). Using this technique the prostatogenic isoenzyme is elevated in 50% of stage A and in 80% of stage B carcinoma, suggesting RIA for screening. Erythrocyte sedimentation rate or serum iron and copper are not necessarily of prognostic value. Phosphatase determination of bone marrow aspirates also requires the RIA method if differentiation of stage C and D is to be expected. Serum hormone assays are not yet introduced into routine staging programs. Serum and urinary markers such as CEA, polyamines of LDH isoenzymes are unspecific and of uncertain value in prostatic carcinoma. Measurement of urinary hydroxyproline seems a reliable method for the search of osseous spread; other bone diseases have to be excluded. In patients with prostate cancer laboratory tests still represent adjunctive measures in connection with the clinical diagnostic armamentarium of urologists.

Topics: Acid Phosphatase; Alkaline Phosphatase; Androstanes; Bone Marrow; Carcinoembryonic Antigen; False Negative Reactions; Humans; Hydroxyproline; Isoenzymes; Isoleucine; Male; Polyamines; Prostatic Neoplasms; Radioimmunoassay

The cell line EB 33 was cultivated from the tissue of a human prostate adenocarcinoma in June 1973. Since that time, efforts have been made by scientists in several laboratories to characterize this line by morphologic, biochemical, endocrinologic, genetic, and immunologic parameters. The great need for a well-defined prostatic cell line for immunologic experimentation warrants a complete review of the subject.

Topics: Acid Phosphatase; Animals; Cell Line; Chromosome Aberrations; Dihydrotestosterone; Epithelium; Glucosephosphate Dehydrogenase; Humans; Immunity; Male; Mice; Mice, Nude; Neoplasm Transplantation; Neoplasms, Experimental; Neoplasms, Hormone-Dependent; Prostatic Neoplasms; Transplantation, Heterologous

Topics: Acid Phosphatase; Adenocarcinoma; Age Factors; Aged; Alkaline Phosphatase; Ethnicity; Gonadal Steroid Hormones; History, 19th Century; History, 20th Century; Humans; Male; Middle Aged; Oxidoreductases; Prostatic Neoplasms

A summary is presented of those organ specific enzyme assays traditionally used in evaluation of the patient with cancer. In addition, the use of certain serum enzymes such as gamma-glutamyl transpeptidase, phosphohexose isomerase or 5'-nucleotidase as aids in following the course of the disease, particularly in patients with metastatic spread to the liver is outlined. Also considered is the utility of enzyme analysis in biopsy tissue, biologic fluids, and washings of body cavities. Newer enzymes are considered which might, in the future, be developed as diagnostic tools or as probes for the understanding of the etiology of cancer.

Topics: Acid Phosphatase; Alkaline Phosphatase; Amylases; Aryl Hydrocarbon Hydroxylases; Bone Neoplasms; Clinical Enzyme Tests; gamma-Glutamyltransferase; Humans; Isoenzymes; Isomerases; Leucyl Aminopeptidase; Lipase; Liver Neoplasms; Lung Neoplasms; Male; Muramidase; Neoplasms; Nucleotidases; Oxidoreductases; Pancreatic Neoplasms; Prostatic Neoplasms; Sulfatases

Topics: Acid Phosphatase; Adult; Aged; Diethylstilbestrol; Estradiol; Female; Gaucher Disease; Humans; Isoenzymes; Male; Methods; Middle Aged; Prostatic Neoplasms

Topics: Acid Phosphatase; Animals; Body Fluids; Bulbourethral Glands; Cattle; Citrates; Dihydrotestosterone; Dogs; Fructose; Humans; Inositol; Male; Potassium; Prostaglandins; Prostate; Prostatic Neoplasms; Proteins; Putrescine; Rats; Secretory Rate; Semen; Seminal Vesicles; Species Specificity; Spermatozoa; Spermine; Swine; Testicular Diseases; Testosterone

Topics: Acid Phosphatase; Blood Platelet Disorders; Bone and Bones; Bone Diseases; Breast Neoplasms; Electrophoresis, Polyacrylamide Gel; Erythrocytes; Female; Hematologic Diseases; Humans; Isoenzymes; Leukemia; Leukocytes; Lipidoses; Male; Primary Myelofibrosis; Prostate; Prostatic Neoplasms; Spleen; Thromboembolism

Topics: Acid Phosphatase; Bone and Bones; Bone Neoplasms; Histocytochemistry; Humans; Hydronephrosis; Immunodiffusion; Lymphatic Metastasis; Male; Prostate; Prostatic Neoplasms; Radiography; Radionuclide Imaging; Urination Disorders

Topics: Acid Phosphatase; Adenocarcinoma; Aniline Compounds; Bone Neoplasms; Cyclophosphamide; Evaluation Studies as Topic; Fluorouracil; Humans; Hypercalcemia; Hypophysectomy; Male; Mechlorethamine; Neoplasm Metastasis; Plicamycin; Prostatic Neoplasms

Topics: 17-Ketosteroids; Acid Phosphatase; Adrenalectomy; Adrenocorticotropic Hormone; Animals; Castration; Cortisone; Gold Isotopes; Growth Hormone; Humans; Hypophysectomy; Luteinizing Hormone; Male; Pituitary Irradiation; Prolactin; Prostate; Prostatic Neoplasms; Radioisotopes; Rats; Remission, Spontaneous

Topics: Acid Phosphatase; Clinical Enzyme Tests; Humans; Male; Prostatic Neoplasms

Topics: 17-Hydroxycorticosteroids; 17-Ketosteroids; Acid Phosphatase; Adrenal Gland Neoplasms; Alkaline Phosphatase; Amino Acids; Amylases; Bone Neoplasms; Breast Neoplasms; Carcinoid Tumor; Catecholamines; Chorionic Gonadotropin; Clinical Enzyme Tests; Clinical Laboratory Techniques; Female; Glucose-6-Phosphate Isomerase; Humans; Hydroxyindoleacetic Acid; L-Lactate Dehydrogenase; Liver Neoplasms; Male; Neoplasms; Neoplasms, Nerve Tissue; Neuroblastoma; Nucleotidases; Pancreatic Neoplasms; Pheochromocytoma; Pregnancy; Prostatic Neoplasms; Trophoblastic Neoplasms; Vanilmandelic Acid

Topics: Acid Phosphatase; Clinical Enzyme Tests; Ethanol; Formaldehyde; Glycerophosphates; Hot Temperature; Humans; Hydrogen-Ion Concentration; Male; Methods; Phosphates; Prostatic Neoplasms; Tartrates

Topics: Acid Phosphatase; Citrates; DNA; Glycolysis; Humans; Male; Oxidoreductases; Oxygen Consumption; Prostate; Prostatic Hyperplasia; Prostatic Neoplasms; Testosterone; Zinc

Topics: Acid Phosphatase; Alkaline Phosphatase; Animals; Bone Marrow; Escherichia coli; Gastric Mucosa; Humans; Kidney; Liver; Liver Cirrhosis; Liver Neoplasms; Male; Nucleic Acids; Nucleotides; Plants; Prostatic Neoplasms; Rickets

Topics: Acid Phosphatase; Alkaline Phosphatase; Biopsy; Castration; Clinical Enzyme Tests; Diagnosis, Differential; Fructose-Bisphosphate Aldolase; Glucose-6-Phosphate Isomerase; Glycolysis; Humans; Immune Sera; Isoenzymes; L-Lactate Dehydrogenase; Male; Prostatic Neoplasms; Transaminases

Topics: Acid Phosphatase; Alkaline Phosphatase; Aminopeptidases; Amylases; Biopsy; Glucose-6-Phosphate Isomerase; Glutathione Reductase; Humans; Hyperplasia; Isoenzymes; L-Lactate Dehydrogenase; Male; Neoplasm Metastasis; Phosphoglucomutase; Prognosis; Prostatic Neoplasms; Ribonucleases

Topics: Acid Phosphatase; Adenocarcinoma; Alkaline Phosphatase; Biopsy; Bone Neoplasms; Citrates; Cytodiagnosis; Humans; L-Lactate Dehydrogenase; Lactates; Male; Neoplasm Metastasis; Prostatic Neoplasms; Strontium Isotopes; Urography

Topics: Acid Phosphatase; Clinical Enzyme Tests; Humans; Male; Prostatic Neoplasms

Topics: Acid Phosphatase; Humans; Male; Prostate; Prostatic Neoplasms

Topics: 17-Ketosteroids; Acid Phosphatase; Adrenal Cortex Hormones; Alkaline Phosphatase; Bone Neoplasms; Castration; Estrogens; Geriatrics; Humans; Hypophysectomy; Male; Neoplasm Metastasis; Prostatic Neoplasms; Surgical Procedures, Operative; Urine

Immunotherapies have demonstrated clinical benefit for many types of cancers, however many patients do not respond, and treatment-related adverse effects can be severe. Hence many efforts are underway to identify treatment predictive biomarkers. We have reported the results of two phase I trials using a DNA vaccine encoding prostatic acid phosphatase (PAP) in patients with biochemically recurrent prostate cancer. In both trials, persistent PAP-specific Th1 immunity developed in some patients, and this was associated with favorable changes in serum PSA kinetics. In the current study, we sought to determine if measures of antigen-specific or antigen non-specific immunity were present prior to treatment, and associated with subsequent immune response, to identify possible predictive immune biomarkers.. Patients who developed persistent PAP-specific, IFNγ-secreting immune responses were defined as immune "responders." The frequency of peripheral T cell and B cell lymphocytes, natural killer cells, monocytes, dendritic cells, myeloid derived suppressor cells, and regulatory T cells were assessed by flow cytometry and clinical laboratory values. PAP-specific immune responses were evaluated by cytokine secretion in vitro, and by antigen-specific suppression of delayed-type hypersensitivity to a recall antigen in an in vivo SCID mouse model.. The frequency of peripheral blood cell types did not differ between the immune responder and non-responder groups. Non-responder patients tended to have higher PAP-specific IL-10 production pre-vaccination (p = 0.09). Responder patients had greater preexisting PAP-specific bystander regulatory responses that suppressed DTH to a recall antigen (p = 0.016).. While our study population was small (n = 38), these results suggest that different measures of antigen-specific tolerance or regulation might help predict immunological outcome from DNA vaccination. These will be prospectively evaluated in an ongoing randomized, phase II trial.

Topics: Acid Phosphatase; Animals; Antigens, Neoplasm; Biomarkers, Tumor; Cancer Vaccines; Humans; Immunity, Cellular; Immunogenicity, Vaccine; Immunophenotyping; Interferon-gamma; Interleukin-10; Leukocyte Count; Leukocytes, Mononuclear; Male; Mice, SCID; Prostatic Neoplasms; Vaccines, DNA

Androgen deprivation therapy (ADT) for prostate cancer increases fracture risk, decreases bone mineral density, and increases bone turnover markers (BTMs) including serum type 1 C-telopeptide (sCTX), tartrate-resistant alkaline phosphatase 5b (TRAP-5b), and procollagen-1 N-terminal telopeptide (P1NP). In a prespecified exploratory analysis of a phase 3, multicenter, double-blind study, we evaluated the effects of denosumab (60 mg subcutaneously every 6 months for 3 years) versus placebo (1468 patients, 734 in each group) on BTM values. BTMs were measured at baseline, month 1, and predose at months 6, 12, 24, and 36 in the overall population. BTMs at month 1 are also reported for subgroups based on age (<  70 years versus ≥  70 years), prior duration of ADT (≤  6 months versus > 6 months), and baseline BTM (≤  median versus >  median BTM values). Treatment with denosumab provided a rapid and sustained decrease of BTM values compared with placebo. The median change in sCTX levels at month 1 was -90% in the denosumab group and -3% in the placebo group (p  <  0.0001). The median change in TRAP-5b levels at month 1 was -55% in the denosumab group and -3% in the placebo group (p <  0.0001). The maximal median change in P1NP was -64% in the denosumab group and -11% in the placebo group, (p  <  0.0001). Significantly greater decreases in BTM for denosumab were also seen in subgroup analyses based on age, prior ADT treatment, and baseline BTM values. Suppression of bone turnover markers was consistent with marked increases in bone mineral density reported previously.

Topics: Acid Phosphatase; Aged; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Biomarkers; Bone Density; Bone Remodeling; Collagen Type I; Denosumab; Humans; Isoenzymes; Male; Peptide Fragments; Peptides; Procollagen; Prostatic Neoplasms; Statistics, Nonparametric; Tartrate-Resistant Acid Phosphatase

To investigate the clinical safety and effects of auto-dendritic cells pulsed with HLA-A201-binding peptides prostate-specific antigen (PSA) , prostate-specific membrane antigen (PSMA) and prostatic acid phosphatase (PAP) in the treatment of hormone-refractory metastatic prostate cancer (HRPC).. Sixteen HRPC patients with positive HLA-A201 were enrolled and their monocytes isolated and induced into dendritic cells with the combination of rhGM-CSF and rhIL4. The patients were inoculated subcutaneously near the inguinal region with auto-DCs pulsed with peptides PSA (KLQCVDLHV) , PSMA (ALDVYNGL L) and PAP (LLHETDSAV) every 2 weeks for 4 times, and the immunological and clinical responses were examined within 1 -2 weeks after the final vaccination.. Vaccination of dendritic cells was well tolerated and no toxicity was observed. The cytokine levels in the serum such as IL-2, IL-12 and IFN-gamma were significantly increased after the vaccination (P < 0.01). The delayed type hyper- sensitivity (DTH) test was positive in 4 of the patients (4/11), the percentage of antigen-special IFN-gamma+ CD8+ T increased in 5 (5/11), the level of the tumor marker PSA decreased in 6 (6/16) , hydrops abdominis reduced in 1 (1/16), and the size of the cervical lymph node lessened in 1 (1/16). Three patients showed partial remission (PR), 7 stability of the disease (SD), and the other 6 progression of the disease (PD).. Auto-DC vaccines loaded with PSA, PSMA and PAP peptides, capable of eliciting specific immune responses in HRPC patients, is a safe and effective option for the treatment of advanced HRPC.

Topics: Acid Phosphatase; Aged; Antigens, Surface; Cancer Vaccines; CD8-Positive T-Lymphocytes; Cytokines; Dendritic Cells; Glutamate Carboxypeptidase II; HLA-A2 Antigen; Humans; Male; Middle Aged; Prostate-Specific Antigen; Prostatic Neoplasms; Protein Tyrosine Phosphatases; Treatment Outcome

Prostatic acid phosphatase (PAP) is a prostate tumor antigen. We have previously demonstrated that a DNA vaccine encoding PAP can elicit antigen-specific CD8+ T cells in rodents. We report here the results of a phase I/IIa trial conducted with a DNA vaccine encoding human PAP in patients with stage D0 prostate cancer.. Twenty-two patients were treated in a dose-escalation trial with 100 microg, 500 microg, or 1,500 microg plasmid DNA, coadministered intradermally with 200 microg granulocyte-macrophage colony-stimulating factor as a vaccine adjuvant, six times at 14-day intervals. All patients were observed for 1 year after treatment.. No significant adverse events were observed. Three (14%) of 22 patients developed PAP-specific IFN gamma-secreting CD8+ T-cells immediately after the treatment course, as determined by enzyme-linked immunospot. Nine (41%) of 22 patients developed PAP-specific CD4+ and/or CD8+ T-cell proliferation. Antibody responses to PAP were not detected. Overall, the prostate-specific antigen (PSA) doubling time was observed to increase from a median 6.5 months pretreatment to 8.5 months on-treatment (P = .033), and 9.3 months in the 1-year post-treatment period (P = .054).. The demonstration that a DNA vaccine encoding PAP is safe, elicits an antigen-specific T-cell response, and may be associated with an increased PSA doubling time suggests that a multi-institutional phase II trial designed to evaluate clinical efficacy is warranted.

Topics: Acid Phosphatase; Adenocarcinoma; Adjuvants, Immunologic; Adult; Aged; Cancer Vaccines; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Immunotherapy; Injections, Intradermal; Interferon-gamma; Male; Maximum Tolerated Dose; Middle Aged; Neoplasm Staging; Prostate-Specific Antigen; Prostatic Neoplasms; Protein Tyrosine Phosphatases; Recombinant Proteins; Time Factors; Treatment Outcome; Vaccines, DNA

To report the results of a trial comparing the efficacy of triptorelin and surgical castration in the treatment of locally advanced or metastatic prostate cancer.. 80 patients with previously untreated locally advanced or metastatic prostate cancer prostate cancer were included in a one-year multicentre, randomized, prospective, open-label therapeutic trial. Patients either received a monthly injection of triptorelin (group 1; n = 40), or were treated by pulpectomy (group 2; n = 40). Patients were reviewed every 3 months, then every 6 months.. The mean age of the patients was 71.22 +/- 8.25 years. At 1 month, 38 patients were castrated (plasma testosterone < 0.5 mg/ml) in the pulpectomy group versus 35 in the triptorelin group. The mean follow-up was 38.8 +/- 26 months in the triptorelin group and 36.3 +/- 25 months in the pulpectomy group. On multivariate analysis, age, impaired performance status and PAP level (> 3.2 ng/ml) were predictive factors of a poor outcome. The median survival was 37.5 +/- 9 months in the triptorelin group and 33 +/- 3 months in the pulpectomy group. At 3 years, no significant difference in specific survival was observed between the 2 groups. At 8 years of follow-up, 63 patients had died.. This study demonstrates an equivalent specific survival between patients treated by triptorelin or surgical castration. Castration is rapidly obtained with triptorelin (< 2 months) and is maintained over time throughout the duration of treatment.

Topics: Acid Phosphatase; Age Factors; Aged; Antineoplastic Agents, Hormonal; Follow-Up Studies; Forecasting; Humans; Male; Neoplasm Metastasis; Neoplasm Staging; Orchiectomy; Prospective Studies; Prostatic Neoplasms; Protein Tyrosine Phosphatases; Survival Rate; Testis; Testosterone; Treatment Outcome; Triptorelin Pamoate

Docetaxel has activity against androgen-independent prostate cancer and preclinical studies have shown that taxane-based chemotherapy can enhance antitumor response of vaccines. The primary objective of this study was to determine if concurrent docetaxel (with dexamethasone) had any effect on generating an immune response to the vaccine. Secondary end points were whether vaccine could be given safely with docetaxel and the clinical outcome of the treatment regimen.. The vaccination regimen was composed of (a) recombinant vaccinia virus (rV) that expresses the prostate-specific antigen gene (rV-PSA) admixed with (b) rV that expresses the B7.1 costimulatory gene (rV-B7.1), and (c) sequential booster vaccinations with recombinant fowlpox virus (rF-) containing the PSA gene (rF-PSA). Patients received granulocyte macrophage colony-stimulating factor with each vaccination. Twenty-eight patients with metastatic androgen-independent prostate cancer were randomized to receive either vaccine and weekly docetaxel or vaccine alone. Patients on the vaccine alone arm were allowed to cross over to receive docetaxel alone at time of disease progression. The ELISPOT assay was used to monitor immune responses for PSA-specific T cells.. The median increase in these T-cell precursors to PSA was 3.33-fold in both arms following 3 months of therapy. In addition, immune responses to other prostate cancer-associated tumor antigens were also detected postvaccination. Eleven patients who progressed on vaccine alone crossed over to receive docetaxel at time of progression. Median progression-free survival on docetaxel was 6.1 months after receiving vaccine compared with 3.7 months with the same regimen in a historical control.. This is the first clinical trial to show that docetaxel can be administered safely with immunotherapy without inhibiting vaccine specific T-cell responses. Furthermore, patients previously vaccinated with an anticancer vaccine may respond longer to docetaxel compared with a historical control of patients receiving docetaxel alone. Larger prospective clinical studies will be required to validate these findings.

Topics: Acid Phosphatase; Aged; Aged, 80 and over; Androgens; Antigens; Antigens, Neoplasm; Antigens, Surface; Antineoplastic Agents, Phytogenic; Cancer Vaccines; Combined Modality Therapy; Cross-Over Studies; Disease-Free Survival; Docetaxel; Glutamate Carboxypeptidase II; Glycoproteins; Humans; Leukocytes, Mononuclear; Male; Middle Aged; Mucin-1; Mucins; Neoplasm Metastasis; Prostate-Specific Antigen; Prostatic Neoplasms; Taxoids; Time Factors; Treatment Outcome; Vaccination

Dendritic cell (DC)-based immunotherapy is a promising approach to augment tumor antigen-specific T cell responses in cancer patients. However, tumor escape with down-regulation or complete loss of target antigens may limit the susceptibility of tumor cells to the immune attack. Concomitant generation of T cell responses against several immunodominant antigens may circumvent this potential drawback. In this trial, we determined the immunostimulatory capacity of autologous DC pulsed with multiple T cell epitopes derived from four different prostate-specific antigens in patients with advanced hormone-refractory prostate cancer.. Autologous DC of HLA-A*0201(+) patients with hormone-refractory prostate cancer were loaded with antigenic peptides derived from prostate stem cell antigen (PSCA(14-22)), prostatic acid phosphatase (PAP(299-307)), prostate-specific membrane antigen (PSMA(4-12)), and prostate-specific antigen (PSA(154-163)). DC were intradermally applied six times at biweekly intervals followed-in the case of an enhanced immune response-by monthly booster injections. Immune monitoring during the time of ongoing vaccinations (12-59 weeks) included ex vivo ELISPOT measurements, MHC tetramer analysis and in vitro cytotoxicity assays.. Of the initial six patients, three qualified for long-term multi-epitope DC vaccination. This regime was tolerated well by all three patients. The vaccination elicited significant cytotoxic T cell responses against all prostate-specific antigens tested. In addition, memory T cell responses against the control peptides derived from influenza matrix protein and tetanus toxoid were efficiently boosted. Clinically, the long-term DC vaccination was associated with an increase in PSA doubling time.. DC-based multi-epitope immunotherapy with repeated boosting in men with hormone-refractory prostate carcinoma is feasible and generates efficient cellular antitumor responses.

Topics: Acid Phosphatase; Aged; Antigens, Neoplasm; Antigens, Surface; Cancer Vaccines; Carcinoma; Dendritic Cells; Glutamate Carboxypeptidase II; GPI-Linked Proteins; HLA-A Antigens; HLA-A2 Antigen; Humans; Immunodominant Epitopes; Immunotherapy, Adoptive; Male; Membrane Glycoproteins; Middle Aged; Neoplasm Proteins; Prostate-Specific Antigen; Prostatic Neoplasms; Protein Tyrosine Phosphatases

APC8015 (sipuleucel-T) is a cellular prostate cancer vaccine containing autologous antigen-presenting cells (APC) loaded with PA2024, a recombinant prostatic acid phosphatase/granulocyte-macrophage-colony-stimulating factor fusion protein, as the immunogen. Bevacizumab is a recombinant antibody against vascular endothelial growth factor, a proangiogenic protein with inhibitory effects on APC. A clinical trial was conducted to determine the prostate-specific antigen (PSA) and immunomodulatory effects of this combination immunotherapy.. Patients with androgen-dependent prostate cancer who had received prior definitive therapy with nonmetastatic, recurrent disease as manifested by a rising PSA of between 0.4 ng/mL and 6.0 ng/mL were enrolled. APC8015 was given intravenously(i.v.) on Weeks 0, 2, and 4. Bevacizumab was given at a dose of 10 mg/kg i.v. on Weeks 0, 2, 4, and every 2 weeks thereafter until toxicity or disease progression. PSA changes were recorded and the PSA doubling time (PSADT) was calculated. Immune response versus PA2024 was measured at baseline and after treatment by T-cell proliferation and interferon-gamma enzyme-linked immunospot (ELISPOT) assays.. Twenty-two patients were treated. One patient achieved a > or =50% decrease in PSA. Nine patients exhibited some decrease in PSA from baseline, ranging from 6% to 72%, with the PSA of 3 patients decreasing at least 25%. The median pretreatment PSADT for the 20 evaluable patients was 6.9 months and the median posttreatment PSADT was 12.7 months (P = .01). All patients demonstrated induction of an immune response against PA2024.. The combination of APC8015 and bevacizumab induces an immune response and modulates PSA in patients with biochemically recurrent prostate cancer.

Topics: Acid Phosphatase; Aged; Angiogenesis Inhibitors; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antigen-Presenting Cells; Bevacizumab; Cancer Vaccines; Combined Modality Therapy; Disease Progression; Humans; Immunotherapy; Lymphocyte Activation; Male; Middle Aged; Prostate-Specific Antigen; Prostatic Neoplasms; Protein Tyrosine Phosphatases; T-Lymphocytes; Tissue Extracts

Prostate cancer is an excellent target for an active vaccine-based approach based on the fact that prostate cancer cells express unique proteins which serve as highly specific targets. APC8015 (Provenge) is one such investigational therapeutic vaccine that uses autologous antigen presenting cells (APCs) loaded with a recombinant fusion protein of prostatic acid phosphatase linked to a molecule that specifically targets a receptor expressed on the surface of human APCs. Clinical trial outcomes have demonstrated activity in patients with androgen independent prostate cancer.

Topics: Acid Phosphatase; Androgens; Autoantigens; Cancer Vaccines; Disease Progression; Follow-Up Studies; Humans; Immunotherapy; Male; Prostatic Neoplasms; Protein Tyrosine Phosphatases; T-Lymphocytes; Treatment Outcome

Topics: Acid Phosphatase; Adenocarcinoma; Adjuvants, Immunologic; CD8-Positive T-Lymphocytes; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Interferon-alpha; Male; Neoplasm Staging; Prostatic Neoplasms; Protein Tyrosine Phosphatases; Treatment Outcome; Vaccines, DNA

Prostate cancer is the most commonly diagnosed malignancy in American men, yet treatment of its metastatic androgen-independent form remains inadequate. This mandates development of new therapies such as immunotherapy. In this Phase 2 trial, we determined the efficacy of antigen presenting cells (APCs) loaded with PA2024, a recombinant fusion protein containing prostatic acid phosphatase (PAP) and GM-CSF.. We enrolled 21 patients with histologically documented androgen-independent prostate carcinoma that could be evaluated by radionuclide bone scan or computed tomography scan. APC8015 was prepared from a leukapheresis product; it contained autologous CD54-positive PA2024-loaded APCs with admixtures of monocytes, macrophages, B and T cells. APC8015 was infused intravenously twice, 2 weeks apart. Two weeks after the second infusion, patients received three subcutaneous injections of 1.0 mg of PA2024 1 month apart. We monitored patients' physical condition, immune response, and laboratory parameters.. Nineteen patients could be evaluated for response to treatment. The median time to progression was 118 days. Treatment was tolerated reasonably well; most adverse effects were secondary to APC8015 and were NCI Common Toxicity Criteria Grade 1-2. Four of the 21 patients reported Grade 3-4 adverse events. Two patients exhibited a transient 25-50% decrease in prostate-specific antigen (PSA). For a third patient, PSA dropped from 221 ng/ml at baseline to undetectable levels by week 24 and has remained so for more than 4 years. In addition, this patient's metastatic retroperitoneal and pelvic adenopathy has resolved. PBMC collected from patients for at least 16 weeks proliferated upon in vitro stimulation by PA2024. For the patient with responsive disease, PBMC could be stimulated for 96 weeks.. This study demonstrates a definite clinical response of androgen-independent prostate cancer to APC immunotherapy. Currently we are studying this mode of therapy in Phase 3 trials.

Topics: Acid Phosphatase; Aged; Aged, 80 and over; Antigen-Presenting Cells; Carcinoma; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Immunotherapy; Infusions, Intravenous; Injections, Subcutaneous; Male; Middle Aged; Neoplasm Metastasis; Prostate-Specific Antigen; Prostatic Neoplasms; Protein Tyrosine Phosphatases; Recombinant Fusion Proteins; Treatment Outcome

To evaluate the efficacy and safety of atrasentan (ABT-627), an endothelin-A receptor antagonist, in the treatment of asymptomatic, hormone-refractory prostatic adenocarcinoma.. A double-blind, randomized, placebo-controlled clinical trial of hormone-refractory prostate cancer (HRPCa) patients was conducted in the United States and Europe. Two hundred eighty-eight asymptomatic patients with HRPCa and evidence of metastatic disease were randomly assigned to one of three study groups receiving a once-daily oral dose of placebo, 2.5 mg atrasentan, or 10 mg atrasentan, respectively. Primary end point was time to progression; secondary end points included time to prostate-specific antigen (PSA) progression, bone scan changes, and changes in bone and tumor markers.. The three treatment groups were similar in all baseline characteristics. Median time to progression in intent-to-treat (ITT) patients (n = 288) was longer in the 10-mg atrasentan group compared with the placebo group: 183 v 137 days, respectively; (P =.13). Median time to progression in evaluable patients (n = 244) was significantly prolonged, from 129 days (placebo group) to 196 days (10-mg atrasentan group; P =.021). For both ITT and evaluable populations in the 10-mg atrasentan group, median time to PSA progression was twice that of the placebo group (155 v 71 days; P =.002). Patients who received placebo continued to have significant increases from baseline in serum (lactate dehydrogenase [LDH]), a marker of disease burden; elevations in LDH were uniformly attenuated by atrasentan in the ITT population. Headache, peripheral edema, and rhinitis were primary side effects, typically of mild to moderate severity. Quality of life was not adversely affected by atrasentan.. Atrasentan is an oral, targeted therapy with favorable tolerability and the potential to delay progression of HRPCa.

Topics: Acid Phosphatase; Adenocarcinoma; Aged; Antineoplastic Agents; Atrasentan; Dose-Response Relationship, Drug; Endothelin Receptor Antagonists; Humans; L-Lactate Dehydrogenase; Male; Prostatic Neoplasms; Pyrrolidines; Receptor, Endothelin A; Treatment Outcome

Dendritic cells (DC) represent potent APCs that are capable of generating tumor-specific immunity. We performed a pilot clinical trial using Ag-pulsed DC as a tumor vaccine. Twenty-one patients with metastatic prostate cancer received two monthly injections of DC enriched and activated from their PBMC. DC were cocultured ex vivo with recombinant mouse prostatic acid phosphatase as the target neoantigen. Following enrichment, DC developed an activated phenotype with up-regulation of CD80, CD86, and CD83 expression. During culture, the DC maintained their levels of various adhesion molecules, including CD44, LFA-1, cutaneous lymphocyte-associated Ag, and CD49d, up-regulated CCR7, but lost CD62 ligand and CCR5. In the absence of CD62 ligand, such cells would not be expected to prime T cells efficiently if administered i.v. due to their inability to access lymphoid tissue via high endothelial venules. To assess this possibility, three patient cohorts were immunized with Ag-pulsed DC by i.v., intradermal (i.d.), or intralymphatic (i.l.) injection. All patients developed Ag-specific T cell immune responses following immunization, regardless of route. Induction of IFN-gamma production, however, was seen only with i.d. and i.l. routes of administration, and no IL-4 responses were seen regardless of route, consistent with the induction of Th1-type immunity. Five of nine patients who were immunized by the i.v. route developed Ag-specific Abs compared with one of six for i.d. and two of six for i.l. routes. These results suggest that while activated DC can prime T cell immunity regardless of route, the quality of this response and induction of Ag-specific Abs may be affected by the route of administration.

Topics: Acid Phosphatase; Antibody Specificity; Cancer Vaccines; Cell Adhesion Molecules; Cells, Cultured; Cytokines; Dendritic Cells; Flow Cytometry; Humans; Injections, Intradermal; Injections, Intralymphatic; Injections, Intravenous; Lymphocyte Activation; Male; Pilot Projects; Prostate; Prostatic Neoplasms; Receptors, Chemokine; Receptors, Lymphocyte Homing; T-Lymphocytes

Many tumor-associated Ags represent tissue differentiation Ags that are poorly immunogenic. Their weak immunogenicity may be due to immune tolerance to self-Ags. Prostatic acid phosphatase (PAP) is just such an Ag that is expressed by both normal and malignant prostate tissue. We have previously demonstrated that PAP can be immunogenic in a rodent model. However, generation of prostate-specific autoimmunity was seen only when a xenogeneic homolog of PAP was used as the immunogen. To explore the potential role of xenoantigen immunization in cancer patients, we performed a phase I clinical trial using dendritic cells pulsed with recombinant mouse PAP as a tumor vaccine. Twenty-one patients with metastatic prostate cancer received two monthly vaccinations of xenoantigen-loaded dendritic cells with minimal treatment-associated side effects. All patients developed T cell immunity to mouse PAP following immunization. Eleven of the 21 patients also developed T cell proliferative responses to the homologous self-Ag. These responses were associated with Ag-specific IFN-gamma and/or TNF-alpha secretion, but not IL-4, consistent with induction of Th1 immunity. Finally, 6 of 21 patients had clinical stabilization of their previously progressing prostate cancer. All six of these patients developed T cell immunity to human PAP following vaccination. These results demonstrate that xenoantigen immunization can break tolerance to a self-Ag in humans, resulting in a clinically significant antitumor effect.

Topics: Acid Phosphatase; Animals; Antigens, Heterophile; Cancer Vaccines; Cytokines; Dendritic Cells; Enzyme-Linked Immunosorbent Assay; Humans; Immunotherapy, Adoptive; Kinetics; Male; Mice; Middle Aged; Prostatic Neoplasms; Protein Tyrosine Phosphatases; Th1 Cells; Treatment Outcome

We attempted to induce therapeutic immunity against prostate-derived tissues in patients suffering from progressive hormone-refractory metastatic prostate carcinoma. Thirteen patients were treated with two infusions, 1 month apart, of autologous dendritic cells (APC8015) preexposed ex vivo to PA2024, a fusion protein consisting of human granulocyte/macrophage-colony stimulating factor (GM-CSF) and human prostatic acid phosphatase (PAP). The infusions were followed by three s.c. monthly doses of PA2024 without cells. Three groups of patients each received PA2024 at 0.3, 0.6, or 1.0 mg/injection. All Ps were two-sided. Treatment was well tolerated. After infusions of APC8015, patients experienced only mild (grade 1-2) short-lived fever and/or chills, myalgia, pain, and fatigue. One patient developed grade 3 fatigue. Four patients developed mild local reactions to s.c. PA2024. Twelve patients were evaluable for response to treatment. Circulating prostate-specific antigen levels dropped in three patients. T cells, drawn from patients after infusions of APC8015, but not before, could be stimulated in vitro by GM-CSF (P = 0.0004) and PAP (P = 0.0001), demonstrating broken immune tolerance against these two normal proteins. Injections of PA2024 did not influence the reactivity of T cells against PAP and GM-CSF. However, antibodies to GM-CSF and, to a much lesser extent, to PAP reached maximum titers only after two or even three injections of PA2024, showing that directly injected PA2024 was involved in stimulation of humoral immunity. Dendritic cells exposed to antigen ex vivo can induce antigen-specific cellular immunity in prostate cancer patients, warranting further studies of this mode of immunotherapy.

Topics: Acid Phosphatase; Antigen-Presenting Cells; Cell Division; Dendritic Cells; Dose-Response Relationship, Drug; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Immunotherapy; Injections, Subcutaneous; Male; Prostate; Prostatic Neoplasms; Recombinant Fusion Proteins; T-Lymphocytes; Time Factors; Transplantation, Autologous

Provenge (Dendreon Corp, Seattle, WA) is an immunotherapy product consisting of autologous dendritic cells loaded ex vivo with a recombinant fusion protein consisting of prostatic acid phosphatase (PAP) linked to granulocyte-macrophage colony-stimulating factor. Sequential phase I and phase II trials were performed to determine the safety and efficacy of Provenge and to assess its capacity to break immune tolerance to the normal tissue antigen PAP.. All patients had hormone-refractory prostate cancer. Dendritic-cell precursors were harvested by leukapheresis in weeks 0, 4, 8, and 24, loaded ex vivo with antigen for 2 days, and then infused intravenously over 30 minutes. Phase I patients received increasing doses of Provenge, and phase II patients received all the Provenge that could be prepared from a leukapheresis product.. Patients tolerated treatment well. Fever, the most common adverse event, occurred after 15 infusions (14.7%). All patients developed immune responses to the recombinant fusion protein used to prepare Provenge, and 38% developed immune responses to PAP. Three patients had a more than 50% decline in prostate-specific antigen (PSA) level, and another three patients had 25% to 49% decreases in PSA. The time to disease progression correlated with development of an immune response to PAP and with the dose of dendritic cells received.. Provenge is a novel immunotherapy agent that is safe and breaks tolerance to the tissue antigen PAP. Preliminary evidence for clinical efficacy warrants further exploration.

Topics: Acid Phosphatase; Adenocarcinoma; Aged; Aged, 80 and over; Antibodies, Neoplasm; B-Lymphocytes; Cancer Vaccines; Dendritic Cells; Epitopes; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Immunotherapy, Active; Immunotherapy, Adoptive; Lymphocyte Activation; Male; Middle Aged; Prostatic Neoplasms; Recombinant Fusion Proteins; Recombinant Proteins; T-Lymphocytes

Strategies utilized by urologists in managing prostate carcinoma patients after radical prostatectomy vary appreciably. The reason for this is unclear. The authors investigated the effect of practitioner age on management strategies.. From among the total of 12,500 American Urological Association (AUA) members, 4467 were randomly selected to receive a custom-designed survey about their care of prostate carcinoma patients after radical prostatectomy. Respondents were asked to describe their follow-up practices for patients treated with curative intent, their motivations regarding postoperative surveillance, their methods of evaluating a postoperative increase in serum prostate specific antigen (PSA) level, and their choices of treatment for patients with recurrent prostate carcinoma.. One thousand fifty responses were analyzed. There was a statistically significant influence of practitioner age on the management of at-risk patients, but it was quite small. The typical workup for an elevated postoperative serum PSA level also varied significantly according to practitioner age; older urologists ordered more serum prostatic acid phosphatase levels and computed tomography scans of the abdomen and pelvis, whereas younger urologists ordered more bone scans. The treatment of recurrent prostate carcinoma did not vary significantly according to urologist age. The opinions of older urologists regarding the survival benefits of postoperative surveillance were considerably different from the opinions of their younger colleagues.. The results of this study suggest that urologist age accounts for some of the variation in the postoperative management of prostate carcinoma patients. Differences in beliefs regarding the benefits of surveillance may be partially responsible for this. Persuasive clinical research will probably be required to increase the uniformity of practice in this important area.

Topics: Acid Phosphatase; Adult; Age Factors; Data Collection; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Postoperative Care; Prostate-Specific Antigen; Prostatectomy; Prostatic Neoplasms; Urology

To evaluate the efficacy, tolerability, endocrinological effects and the pharmacokinetics of Casodex, when given as monotherapy during daily dosing of 10-200 mg to patients with advanced prostate cancer.. A total of 390 patients with advanced prostate cancer were treated for a minimum of 12 weeks with a daily monotherapy dose of Casodex. The doses ranged from 10 to 200 mg. Objective assessments of efficacy included: review of measurable metastases, prostate dimension, prostatic acid phosphatase and prostate-specific antigen (PSA) levels. Subjective assessments of efficacy included review of urological symptoms, performance status, bone scan and analgesic requirement. Pharmacokinetic samples were taken at various time points up to 3 months, and assayed using an achiral HPLC method.. Clear objective responses were observed, particularly at doses of 50 mg and above. Specifically, the median percentage decrease in PSA at 50 mg was 90.0%, and at 100 and 200 mg it was 93.4 and 94.8%, respectively. Up to 53% of symptomatic patients demonstrated a subjective response at 3 months. Casodex was well tolerated at all doses with no effect on haematological or cardiovascular parameters and no effect on renal function. The expected pharmacological effects of potent antiandrogen therapy, such as breast tenderness (58%), gynaecomastia (48%), and hot flushes (17%), were reported, but these incidences reflected the direct eliciting of these events. The intrinsic efficacy of Casodex was demonstrated despite increases of 60% in testosterone levels. However, this increase reached a plateau after 4-12 weeks of therapy, but the majority of values remained within the normal range. Casodex has a half-life of approximately 1 week, enabling once-daily dosing with no effect of age or renal impairment on its pharmacokinetics.. Casodex has a favourable side effect profile compared with the known safety profiles of other antiandrogens and has demonstrated intrinsic efficacy. Casodex warrants further investigation as a monotherapy for the management of advanced prostate cancer.

Topics: Acid Phosphatase; Androgen Antagonists; Anilides; Antineoplastic Agents; Dose-Response Relationship, Drug; Estradiol; Follicle Stimulating Hormone; Humans; Liver Function Tests; Luteinizing Hormone; Male; Neoplasm Invasiveness; Neoplasm Metastasis; Neoplasm Staging; Nitriles; Prostate-Specific Antigen; Prostatic Neoplasms; Testosterone; Tosyl Compounds

An unblinded, multicenter study to evaluate the efficacy and safety of a long-acting depot formulation of leuprolide (30 mg injected intramuscularly every 16 weeks) was carried out in 49 patients with Stage D2 prostate cancer.. Clinical evaluations were performed every 16 weeks, and serum testosterone levels were monitored biweekly or weekly for 32 weeks.. The mean serum testosterone level for the 45 evaluable patients fell to the castrate range (50 ng/dL or less) by week 3 after the initial depot injection and remained at that level throughout the initial 32-week treatment period. The median time to the onset of castrate levels was 22 days (range 9 to 43). Onset of castrate levels of testosterone was achieved within 4 weeks of the initial depot injection in 96% of patients. One patient (2%) experienced a transient "escape" (testosterone levels greater than 50 ng/dL on two consecutive determinations). Delay of an injection by up to 3 weeks did not have an effect on testosterone suppression. Objective tumor response (no progression) occurred in 90% of patients at week 16 and in 80% at week 32. Prostate-specific antigen and prostatic acid phosphatase decreased by 50% or more at week 32 in 97% and 76% of patients, respectively. Assessment of local disease status and overall performance status showed improvement or stability in most patients. The most common adverse events were hot flashes (45%), back pain (16%), and arthralgia (14%).. The 30-mg depot formulation of leuprolide, which acts in a manner similar to the 7.5- and 22.5-mg depot formulations (given monthly and every 3 months, respectively) is effective in lowering serum testosterone to castrate levels in all patients and demonstrates a favorable response in 80% of the patients with advanced prostate cancer for the 32-week observation period. The drug was well tolerated in all patients.

Topics: Acid Phosphatase; Adenocarcinoma; Aged; Aged, 80 and over; Antineoplastic Agents, Hormonal; Delayed-Action Preparations; Disease Progression; Drug Administration Schedule; Humans; Leuprolide; Luteinizing Hormone; Male; Middle Aged; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Testosterone

This is the final analysis of EORTC GU Group Trial 30843 in which the treatment of advanced, metastatic prostate cancer with a combination of the LHRH agonist buserelin (nasal spray) and cyproterone acetate (Androcur), either continuously of only during the first 2 weeks, was compared with orchidectomy. There was no significant difference between the three arms as far as response rate, time to progression (subjective and objective) and duration of survival are concerned. Retrospective stratification according to the most important prognostic factors did not change the conclusions. Possible reasons for the difference with trial 30853, which used the same entry criteria but compared goserelin and flutamide with orchidectomy, are discussed. Reasons for using cyproterone acetate in combination treatment are the prevention of flare of the disease after LHRH agonists only and the prevention/reduction of toxicity in the form of hot flushes.

Topics: Acid Phosphatase; Administration, Intranasal; Aged; Androgen Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Buserelin; Carcinoma; Cause of Death; Cyproterone Acetate; Disease Progression; Disease-Free Survival; Dose-Response Relationship, Drug; Drug Administration Schedule; Humans; Injections, Subcutaneous; Male; Middle Aged; Orchiectomy; Pain Measurement; Proportional Hazards Models; Prospective Studies; Prostatic Neoplasms; Survival Rate; Treatment Outcome

Prostate specific antigen (PSA), prostatic acid phosphatase and alkaline phosphatase were analyzed in 2 large prospective multicenter and multinational trials to assess their correlation with time to progression and overall survival after hormonal therapy for metastatic carcinoma of the prostate.. A total of 868 patients who underwent medical or surgical castration was randomized to receive an oral antiandrogen (nilutamide) or placebo. The serum markers under study were measured at baseline and at 1, 3, 6 and every 6 months thereafter.. At baseline the strongest predictive factor was serum alkaline phosphatase. Patients with an alkaline phosphatase of 2 or less times normal lived almost twice as long as those with a level of more than 2 times normal (p < 0.0001). The longer survival was observed in patients whose PSA became normal 3 months after initiation of hormonal therapy compared to those whose PSA never reached normal (p < 0.0001).. Serum markers at baseline and during the few months after initiation of hormonal therapy can provide prognostic information for the clinical treatment of patients with metastatic carcinoma of the prostate. In addition, the PSA level at month 3 can serve as a surrogate end point in clinical trials.

Topics: Acid Phosphatase; Alkaline Phosphatase; Androgen Antagonists; Antineoplastic Agents, Hormonal; Bone Neoplasms; Disease Progression; Disease-Free Survival; Humans; Imidazoles; Imidazolidines; Leuprolide; Male; Multivariate Analysis; Orchiectomy; Prognosis; Prospective Studies; Prostate-Specific Antigen; Prostatic Neoplasms; Survival Rate; Time Factors

Somatostatin analogues (SMS-A) have been found to inhibit the growth of experimental tumors, as of prostate cancer, via several mechanisms as antihormonal and direct antimitogenic actions. It was demonstrated also that several SMS-A induce greater prostatic tumor regression with more pronounced histological changes if combined with LHRH analogues or in association with complete androgen blockade (CAB). In a phase II clinical trial we administered, in addition to CAB, SMS-A octreotide in 14 patients with stage D2 (group B) prostate cancer-8 previously hormonally treated (PHT) and 6 without any previous hormone treatment (NPHT); 4 other patients, 3 NPHT and one PHT, were treated with CAB only (group A). Antiandrogen and antitumoral activity followed assaying a) plasma testosterone b) prostatic specific antigen (PSA) c) prostatic acid phosphatase (PAP) levels and d) objective (o) and subjective (s) clinical improvement according to WHO criteria. Somatostatin activity was evaluated assaying Insulin like Growth Factor-1 (IGF-1) and Epidermal Growth Factor (EGF). In group B we observed 3 responses, with the best quality of response (oPR/sCR) among the 6 NPHT-patients (50%) and 3 responses among the PHT-patients (37,5%), two of them with an incomplete PHT. In group A, 2 out of 3 NPHT-patients had a response (oPR/sPR). Among group B patients we observed long symptom-free survival, when they responded (17 months), in comparison to group A patients (12 months), but almost the same total duration of survival in the two groups, 18.5 and 18 months, respectively. EGF and IGF-1 serum levels showed a distinct drop parallel to the decrease of PSA serum levels, among the patients with response vs. nonrespondent patients of group B during the treatment. Although our results showed that octreotide in small doses, in addition to CAB, having mild toxicity, enhance number, quality and perhaps the duration of symptom-free responses in patients with stage 2 prostate cancer, the therapeutic efficacy of this combined treatment remains to be ascertained in wider and better randomized clinical trials.

Topics: Acid Phosphatase; Aged; Aged, 80 and over; Androgen Antagonists; Antineoplastic Agents, Hormonal; Carcinoma; Epidermal Growth Factor; Humans; Insulin-Like Growth Factor I; Male; Middle Aged; Octreotide; Prospective Studies; Prostate-Specific Antigen; Prostatic Neoplasms; Somatostatin; Survival Analysis

The safety, efficacy, and pharmacokinetics of the nonsteroidal antiandrogen bicalutamide were investigated in a Phase II trial in 150 patients with metastatic prostate cancer.. Patients took bicalutamide, 50 mg daily, in an open-label multicenter North American trial.. The objective response rate (modified European Organization on Research and Treatment of Cancer [EORTC] criteria) was 70% (57% partial, 13% stable); 59 (39%) of 150 patients had either a > 90% decrease in prostate-specific antigen (PSA) levels or a decline to < 4 ng/mL. Extent of disease on the bone scan was a significant predictor of response. Patients with < 6 metastatic lesions were more likely to respond. Breast pain and gynecomastia occurred in 76% and 60% of patients, respectively. Gastrointestinal toxicity was very infrequent (diarrhea, 5%) The mean drug plasma concentration was 8528 (+/- 2928) ng/mL.. Bicalutamide, 50 mg daily, was well tolerated and has efficacy in metastatic prostate cancer. The percentage of men who had > 90% decline in PSA levels is less than observed with surgical or medical castration and has led to trials using this antiandrogen at higher doses as monotherapy.

Topics: Acid Phosphatase; Adult; Aged; Aged, 80 and over; Androgen Antagonists; Anilides; Humans; Male; Middle Aged; Nitriles; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Tosyl Compounds

This study was initiated to assess the incidence of chronic complications and histologic and biochemical control following hyperfractionated conformal radiotherapy in patients with locally advanced prostate cancer.. Between October 1991 and October 1994, 49 patients with locally advanced prostate cancer were entered on the first two dose levels of a prospective dose-escalation study using hyperfractionated three dimensional conformal radiotherapy. The first 25 patients received a minimum tumor dose of 78 Gy to the prostate and seminal vesicles in 6 weeks at 1.3 Gy, b.i.d. No increase in chronic toxicity compared with conventional radiotherapy was noted; therefore, an additional 24 patients were treated to a minimum tumor dose of 82.8 Gy to the prostate and seminal vesicles in 7 weeks at 1.15 Gy, b.i.d. Toxicity was scored according to the Radiation Therapy Oncology Group morbidity grading scale. Efficacy was assessed through scheduled postradiation prostate specific antigen values and ultrasound-guided biopsies. The median follow-up for the entire group was 20 months.. The hyperfractionated external radiation was well tolerated with minimal acute morbidity. At 30 months, the actuarial probability of Grade 2 gastrointestinal toxicity was 17%. At 30 months, the actuarial probability of Grade 2 genitourinary toxicity was 16%. There was no statistically significant difference between the two dose levels. No Grade 3 or 4 gastrointestinal or genitourinary toxicity was noted. At 12 months, 84% of patients had a prostate specific antigen < or = 4; and 53% < or = 1 ng/ml. At 12 months, 71% of patients had post radiation biopsies that were either negative (55% or showed a marked therapeutic effect (16%).. The use of hyperfractionated conformal radiotherapy facilitated dose escalation with no increase in chronic toxicity compared to standard doses. The initial tumor response based on prostate specific antigen measurements and postradiation biopsies is highly encouraging. Based on these results, an increase in dose to 87.4 Gy has been planned according to the schema of this ongoing dose escalation study.

Topics: Acid Phosphatase; Adult; Aged; Aged, 80 and over; Antineoplastic Agents, Hormonal; Chemotherapy, Adjuvant; Combined Modality Therapy; Dose-Response Relationship, Radiation; Feasibility Studies; Gonadotropin-Releasing Hormone; Humans; Male; Middle Aged; Prospective Studies; Prostate-Specific Antigen; Prostatic Neoplasms; Radiotherapy Dosage; Radiotherapy, Computer-Assisted

The safety, efficacy and pharmacokinetics of bicalutamide were investigated in 150 patients with stage D2 prostate cancer.. Patients received 50 mg. bicalutamide daily in an open label multicenter North American trial.. The objective response rate (modified European Organization for Research in Cancer Therapy criteria) was 70%. Of 150 patients 59 (39%) met prostate specific antigen criteria for partial response, and 88 (59%) reached treatment failure end points and withdrew. Extent of disease was a significant predictor of response but baseline testosterone was not. Breast pain and gynecomastia developed in 76% and 60% of patients, respectively. Mean drug plasma concentration was 8,528 +/- 2,928 ng/ml.. Bicalutamide (50 mg.) daily was well tolerated and efficacious. However, suboptimal effects on prostate specific antigen have led to additional trials to evaluate monotherapy at higher doses.

Topics: Acid Phosphatase; Adult; Aged; Aged, 80 and over; Anilides; Antineoplastic Agents; Follow-Up Studies; Humans; Male; Middle Aged; Neoplasm Staging; Nitriles; Prostate-Specific Antigen; Prostatic Neoplasms; Time Factors; Tosyl Compounds

Serum prostate specific antigen (PSA) and prostatic acid-phosphatase (PAP) levels in normal controls, and patients with prostate cancer, benign prostate hypertrophy (BPH) and other urological diseases were examined with a newly developed latex turbidimetric immunoassay (LPIA ACE PSA, LPIA ACE PAP, IATRON LABORATORIES, INC., Tokyo, Japan). The advantageous characteristics of this method are small amount (10 microliters) of serum required and short time (about 20 min.) for performing this assay. There was a high linear correlation between LPIA ACE PSA and MARKIT-F PA (r2 = 0.953), between LPIA ACE PSA and TANDEM-E PSA (r2 = 0.881) and between LPIA ACE PAP and ABBOTT-PAP EIA (r2 = 0.946). When the BPH patients (n = 110) were used as negative controls, the cut-off value of PSA was determined to be 4.3 ng/ml. Using this level as the cut-off value, the sensitivity was 78% (42 positive/54 untreated prostate cancer patients), specificity (negative rate in BPH patients) was 95% and efficiency was 89%. In a follow-up study of prostate cancer, the PSA value was elevated above the cut-off value in 68% at the time of clinical progression. These findings suggest that LPIA ACE PSA is a useful tool for serum PSA measurement. The cut-off value of PAP measured with LPIA ACE PAP was 9.0 ng/ml, which was determined by the same method as PSA. The sensitivity, specificity and efficiency ware 39%, 96% and 77%, respectively. These findings indicate that PAP is less useful than PSA in the diagnosis of prostate cancer.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acid Phosphatase; Biomarkers, Tumor; Female; Humans; Immunoassay; Latex Fixation Tests; Male; Nephelometry and Turbidimetry; Prostate-Specific Antigen; Prostatic Neoplasms; Reagent Kits, Diagnostic; Sensitivity and Specificity; Urogenital Neoplasms

Evaluation of the prognostic value of prostatic markers with regard to disease progression after endocrine therapy in patients with prostate carcinoma. A total of 51 patients (21 stage C, 5 stage D1 and 25 stage D2). Endocrine therapy consisted in complete hormonal blockade with flutamide and an LH-RH analog depot (leuprolide). PSA-PAP levels were determined both pre-treatment and during follow-up of patients using radioimmunometric techniques. Follow-up extended for 13 to 62 months (mean 30 months). Death due to progression happened in 24 of 51 patients. Previous PSA levels did not correlate to progression. Changes in PSA levels during treatment and time scope when they occurred were associated to subsequent evolution. Patients with PAP higher than 10 ng/ml at the beginning of therapy experienced higher progression rates (p < 0.05). Decrease of PSA levels by a percentage greater than 80% during the first quarter of treatment relative to initial figures was related to lower progression rates (p < 0.01). Maintenance of high levels in the first six months of treatment predicted a higher progression rate (p < 0.001). The study suggests a better prognosis for patients wit decreased serum PSA rates by a percentage of around 80% after one to three months treatment.

Topics: Acid Phosphatase; Adenocarcinoma; Aged; Androgen Antagonists; Antineoplastic Agents, Hormonal; Flutamide; Follow-Up Studies; Humans; Leuprolide; Male; Prognosis; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms

Androgen deprivation displays the mean therapy of advanced stage prostatic cancer. The development of hormone-resistant disease leads to a fatal tumor progression. High-dose fosfestrol (diethylstilbestrol disphosphate) has been suggested to circumvent hormone resistance and to induce a direct cytotoxic effect. Twenty-one patients with hormone-refractory prostate cancer were enrolled in a phase I trial of continuous infusion of high, daily escalating dose of fosfestrol. Fosfestrol was given in a 3.5 hr infusion in 0.9% normal saline at a starting dose of 1.5 g/d. The dose was increased daily in the same patient according to the following schedule: 1.5, 1.8, 2.4, 3.0, 3.6, 3.9, 4.5, 5.1 and 5.7 g/d. The duration of the infusion was prolonged to 7 or 10.5 hr, if a major side effect occurred. There was neither hematological nor cardiovascular toxicity. The main dose-limiting toxicities were nausea/vomiting in 17 patients, edema in 2 patients, and more than 5% weight gain in 3 patients. The planned maximal dose was reached in 10 patients during a 3.5 hr infusion, and in 3 additional patients, after infusion prolongation. Seven patients experienced a subjective improvement: Prostatic acid phosphatase and prostatic specific antigen decreased in 4 out of 11 and in 7 out of 12 patients, respectively. The suggested dose to phase II trial is 4 g/d in 3.5 hr infusion for a duration of up to 10 days.

Topics: Acid Phosphatase; Adenocarcinoma; Aged; Antineoplastic Agents; Biomarkers, Tumor; Bone Neoplasms; Combined Modality Therapy; Diethylstilbestrol; Drug Resistance; Humans; Infusions, Intravenous; Lung Neoplasms; Lymphatic Metastasis; Male; Middle Aged; Orchiectomy; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms

Among new highly potent antagonistic analogs of luteinizing hormone-releasing hormone (LH-RH), containing neutral hydrophilic D-ureidoalkyl amino acids such as D-Cit and D-Hci at position 6 and free of edematogenic and anaphylactoid reactions, Ac-D-Nal(2)1, D-Ph(4Cl)2, D-Pal(3)3, D-Cit6, D-Ala10 (LH-RH) (SB-75; Cetrorelix) was shown to be one of the most powerful. In this trial, we evaluated the response to 500 micrograms SB-75 given every 12 hr subcutaneously (sc) for 4 weeks in 11 patients with benign prostatic hyperplasia (BPH), and 6 weeks in 6 prostatic cancer patients (2 stage C, 4 stage D2). In patients with BPH presenting with prostatism and urinary outflow obstruction, there was a noticeable clinical improvement after the first week of SB-75 administration. This improvement continued during the course of treatment. Before therapy with SB-75, the serum levels of prostate-specific antigen (PSA) (6.73 +/- 1.46 ng/ml), acid phosphatases, total (12.67 +/- 1.15 U/l), and prostatic (2.27 +/- 0.34 U/l), were mildly elevated, but declined to normal values at 4 weeks: (2.13 +/- 0.59 ng/ml; P < 0.01), (7.68 +/- 0.89 U/l; P < 0.01), and (1.39 +/- 0.18 U/l; P < 0.01), respectively. Mean prostatic volume assessed by ultrasonography showed a significant decrease in all patients from 67.84 +/- 8.86 to 37.92 +/- 8.52 cm3; P < 0.01, which represents a reduction of 44%. In patients with prostate cancer, after the first week of therapy with SB-75, we observed a significant decrease in bone pain, relief in urinary outflow obstruction, and reversal of the signs of prostatism. Subjective improvement continued during the following weeks of treatment, so that the patients no longer needed analgesics. PSA, acid, and alkaline phosphatases gradually fell, achieving nearly normal values at 6 weeks. Initial serum testosterone levels in BPH and prostatic cancer patients were within normal limits, but during treatment with the antagonistic analog SB-75, fell to castration values. A major fall in free testosterone levels was observed after the first dose; the maximal inhibition was seen after 6-12 hr, with a simultaneous decrease in levels of both gonadotropins. Our results show that antagonist SB-75 can be safely administered for prolonged periods of time. The rapid shrinkage of the prostate and concomitant improvement in obstructive symptoms of prostatism obtained with antagonistic analog SB-75 in patients with BPH may decrease the morbidity of prostatic surgery and offer a th

Topics: Acid Phosphatase; Aged; Aged, 80 and over; Biomarkers, Tumor; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Humans; Infusions, Intravenous; Longitudinal Studies; Luteinizing Hormone; Male; Middle Aged; Prostate; Prostate-Specific Antigen; Prostatic Hyperplasia; Prostatic Neoplasms; Testosterone; Ultrasonography; Urination

A retrospective analysis of the results of an aggressive multimodal approach combining radical prostatectomy with adjuvant radiation, chemotherapy, or androgen deprivation therapy for patients with pathologic Stage D1 prostate carcinoma was performed to assess the impact of these therapies on survival, recurrence, local control, and morbidity.. Case records of 76 patients with pathologic Stage D1 tumors were reviewed. All had radical retropubic prostatectomy and were recommended adjuvant therapy based on the pathologic extent of the primary tumor and the number of involved lymph nodes.. With a median follow-up of 7 years, overall survival was estimated to be 88% and 66% at 5 and 10 years, respectively, and equaled age- and race-matched controls. Prostate cancer-specific survival at 5 and 10 years was 88% and 74%, respectively. The probability of developing a clinically detectable recurrence (excluding prostate-specific antigen [PSA]) was 29% and 62% at 5 and 10 years, respectively. When PSA was added to the detection data, the probability of developing a recurrence increased to 58% and 78% at 5 and 10 years, respectively. Recurrence and cause-specific survival correlated with Gleason sum. Univariate analysis of the adjuvant therapies demonstrated no effect on survival, but adjuvant radiation alone and in combination with androgen deprivation increased the time to recurrence. Local control was excellent, surgical morbidity was equivalent to that of all patients undergoing prostatectomy during the same time period, and the morbidity of adjuvant therapy was minimal.. Survival equivalent to age- and race-matched controls, with excellent control of the extensive primary tumor, can be achieved in patients with Stage D1 prostate carcinoma by a combination of radical prostatectomy and radiation therapy without the need for routine androgen deprivation therapy.

Topics: Acid Phosphatase; Adenocarcinoma; Chemotherapy, Adjuvant; Combined Modality Therapy; Diethylstilbestrol; Follow-Up Studies; Humans; Lymphatic Metastasis; Male; Neoplasm Recurrence, Local; Neoplasm Staging; Orchiectomy; Postoperative Complications; Prostate-Specific Antigen; Prostatectomy; Prostatic Neoplasms; Radiotherapy, Adjuvant; Retrospective Studies; Survival Rate

The effects of various chemotherapy regimens on endocrine-therapy-refractory prostate cancer were examined in 64 patients. Chemotherapy was started from the first evidence of relapse. The regimens of the initial chemotherapy were as follows: cisplatin (CDDP, 4 cases) and ifosfamide (4 cases) were given as single agents and vincristine, ifosfamide, and peplomycin (VIP, 8 cases); cyclophosphamide, doxorubicin, and CDDP (CAP, 14 cases); ifosfamide, doxorubicin, and CDDP (IAP, 24 cases); and etoposide, doxorubicin, and CDDP (EAP, 10 cases) were given as combinations. On the basis of the results, the patients were divided into two groups: single agents plus VIP and other combinations. In the CAP, IAP, and EAP groups, the cause-specific survival was similar, and the survival of these groups was longer than that of the single agents plus VIP group. Since patients with a long duration between the start of endocrine therapy and the start of chemotherapy were contained in the CAP, IAP, and EAP groups, comparison was performed without these cases. No difference was found between the two groups, suggesting that no superior regimen was found. The short-term effect was evaluated on the basis of the changes observed in prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP) levels at 3 months after the start of chemotherapy, and patients showing a complete response, partial response, or no change on any of the regimens exhibited longer survival than did those with progressive disease. Since the PSA doubling time estimated before the chemotherapy correlated with the change in the PSA values due to the chemotherapy, the rate of proliferation of the tumor influenced the effect of the chemotherapy. Thus, this finding suggests that slowly growing cancers show a better response to chemotherapy than do rapidly proliferating ones.

Topics: Acid Phosphatase; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cisplatin; Cyclophosphamide; Doxorubicin; Estrogens; Etoposide; Follow-Up Studies; Humans; Ifosfamide; Male; Middle Aged; Neoplasm Recurrence, Local; Orchiectomy; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Survival Rate; Vincristine

Fundamental and clinical studies of serum prostatic acid phosphatase (PAP) detected by a Delfia PAP kit were performed. The system is a time-resolved fluoroimmunoassay using europium as a tracer. The lower limit of detection was 0.2 ng/ml. Sera from 54 patients with prostate cancer, 20 with benign prostatic hypertrophy, 20 with urological malignancies other than prostate cancer and 140 adult males over 46 years old were determined. From the mean + 2 S.D. of serum PAP values obtained on the adult males, 1.5 ng/ml was considered as the upper normal level of adult males. By calculating the efficiency and ROC curve using the PAP values of prostate cancer and benign prostatic cancer, 2.5 ng/ml was decided as a cut-off value of this kit. The positive rates of adult males, prostate cancer, benign prostatic cancer and urological malignancies other than prostate cancer were 0.7%, 65%, 20% and 10%, respectively. The sensitivity of stage A2, B2, C and D1 + D2 was, 0%, 0%, 64% and 83%, respectively. The efficiency of the Delfia PAP kit was 52% and that of the Markit M PA kit was 71%. The correlation between the values assayed with the Delfia PAP kit and the Dinabot PAP kit was very high; the value obtained with the Delfia PAP kit was about 80% of that obtained with the Dinabot PAP kit.

Topics: Acid Phosphatase; Aged; Aged, 80 and over; Biomarkers, Tumor; Europium; Fluorescent Antibody Technique; Humans; Male; Middle Aged; Predictive Value of Tests; Prostate; Prostatic Hyperplasia; Prostatic Neoplasms; Reagent Kits, Diagnostic; ROC Curve; Sensitivity and Specificity

Bone scintigraphy is often performed to assess the response to systemic therapy of bone metastasis from prostate cancer. We examined the changes in bone scintigraphic findings and the agreement with AIP, AcP, or other tumor markers measured in the follow-up of patients with known bone metastasis after hormonal therapy. Out of 32 patients, 22 (69%) showed improved scintigraphic findings on the first follow-up bone scintigraphy after hormonal therapy. However, 7 out of 22 patients who showed improvement on the first follow-up scintigraphy, deteriorated thereafter. Changes in the scintigraphic findings were closely correlated with those in the measured tumor markers except for patients with small bone metastasis. Though there were no significant differences in the agreement ratios of the 6 tumor markers evaluated, AIP might be a practical and acceptable indicator. Bone X-ray findings did not change at all in almost half of the cases though the scintigraphic findings showed improvement or deterioration.

Topics: Acid Phosphatase; Aged; Alkaline Phosphatase; Biomarkers, Tumor; Bone and Bones; Bone Neoplasms; Estrogens; Follow-Up Studies; Humans; Male; Orchiectomy; Prostate-Specific Antigen; Prostatic Neoplasms; Prostatic Secretory Proteins; Proteins; Radiography; Radioimmunoassay; Radionuclide Imaging; Seminal Plasma Proteins; Time Factors

To assess the impact of prognostic factors, including continued (orchiectomy) versus discontinued androgen-suppression (nonorchiectomy) therapy, on chemotherapy response and survival of patients with hormone-refractory prostate cancer.. Analysis of five consecutive Southwest Oncology Group (SWOG) phase II chemotherapy trials was undertaken.. Two hundred five hormone-refractory patients were evaluated. Eighty-four percent had been orchiectomized. The median survival durations for the nonorchiectomy and orchiectomy patients were 6 and 7 months, respectively (P = .73). In a univariate analysis, orchiectomy patients had a significantly longer median time from diagnosis to first hormone therapy (1.1 v 0.1 years, P = .003), were more likely to have had chemotherapy initiated > or = 2 years from diagnosis (75% v 56%, P = .03), had a lower incidence of liver metastases (16% v 30%, P = .05), and had lower likelihood of being black (8% v 18%, P = .05) when compared with the nonorchiectomy group. Orchiectomy patients had a marginally significant longer median time from initial hormone treatment, more prior endocrine manipulations, lower median baseline alkaline phosphatase levels, and a lower likelihood of response to chemotherapy when compared with the nonorchiectomy group. Absence of liver metastases (P = .004), hemoglobin level > or = 10 g/dL (P < .001), acid phosphatase level > or = 1.2 IU/L (P = .05), response to chemotherapy (P = .001), and > or = 2 years from initial hormone treatment (P = .01) are important factors for survival.. This study failed to show obvious advantages in response to chemotherapy or survival for patients with continued gonadal suppression. A prospective randomized trial is suggested to evaluate the effect of this factor on progression-free and overall survival of patients with hormone-refractory prostate cancer receiving chemotherapy.

Topics: Acid Phosphatase; Aged; Aged, 80 and over; Analysis of Variance; Androgen Antagonists; Antineoplastic Agents; Drug Resistance; Hemoglobins; Humans; Liver Neoplasms; Male; Middle Aged; Orchiectomy; Prognosis; Prostatic Neoplasms; Remission Induction; Survival Rate; United States

The efficacy and tolerance of the nonsteroidal antiandrogen nilutamide in the treatment of prostatic cancer were studied in a large double-blind clinical trial initiated in 1986. Patients with metastatic prostatic cancer without prior endocrine manipulation underwent orchiectomy and were randomized to 1 of 2 groups receiving nilutamide (225 patients) or placebo (232). Nilutamide and placebo were evaluated for efficacy in 207 and 216 patients, respectively. Progression-free survival was significantly longer in the nilutamide group (median time to progression 20.8 months on nilutamide and 14.9 months on placebo, p = 0.005). Median time to death from prostatic cancer was 30.0 months in the placebo group and 37 months in the nilutamide group. Objective regressions were higher in the nilutamide group (41%) than in the placebo group (24%). Significant differences in favor of the nilutamide group were found at several intervals for bone pain, prostatic acid phosphatase, prostate specific antigen, alkaline phosphatase and bone scan isotope uptake. Nilutamide and orchiectomy constitute a more effective treatment for metastatic prostatic cancer than orchiectomy alone, and the adverse effects of nilutamide, usually minor, are outweighed by the significant improvements in most disease measures and progression-free survival.

Topics: Acid Phosphatase; Actuarial Analysis; Aged; Aged, 80 and over; Antineoplastic Agents; Bone Neoplasms; Combined Modality Therapy; Double-Blind Method; Follow-Up Studies; Humans; Imidazoles; Imidazolidines; Male; Middle Aged; Orchiectomy; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Survival Analysis

In response to the first administration of a luteinizing hormone-releasing hormone (LHRH) agonist, the secretion of pituitary gonadotropin increases sharply and gives rise to a transient surge in the concentration of serum testosterone. This effect reaches a peak 4 to 7 days after the start of therapy and results in the onset of clinical symptoms and signs of tumor flare in 5% to 10% of patients.. To determine whether the effects of the LHRH-induced flare reaction are preventable, cyproterone acetate (100 mg) and low-dose diethylstilbestrol (0.1 mg) were administered daily for 4 weeks to inhibit the pituitary before the initiation of therapy with a depot LHRH agonist, goserelin acetate (3.6 mg every 4 weeks). Diethylstilbestrol was stopped after 8 weeks to eliminate associated minor toxicity while administration of cyproterone acetate was continued to suppress vasomotor symptoms. Twenty-four men with histologically confirmed prostate cancer were enrolled in the study: 6 with Stage C, 2 with Stage D1, and 16 with Stage D2 disease.. Lead-in therapy reduced the concentration of serum testosterone into the castrate range within 1 week, and no significant change was observed in the mean level after administration of goserelin acetate. Neither was there an effect on the initial rate of normalization of serum prostate specific antigen (PSA); normal PSA values were obtained in 50% of patients after 10 weeks and in 70% after 32 weeks. In the subgroup of patients with Stage D2 disease, longer median survival was predicted by a normal serum PSA, either stable or decreasing, after 32 weeks of treatment. The regimen was well tolerated with a low incidence of hot flushes.. These results imply that in the absence of LHRH-induced tumor flare, prognosis is related to the ability of therapy to maintain a PSA nadir in the normal range.

Topics: Acid Phosphatase; Adult; Aged; Aged, 80 and over; Cyproterone Acetate; Diethylstilbestrol; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Goserelin; Humans; Luteinizing Hormone; Male; Middle Aged; Neoplasm Staging; Pilot Projects; Pituitary Gland; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Remission Induction; Survival Rate; Testosterone

Hormone-refractory metastatic prostate cancer remains a therapeutic challenge. Cyclophosphamide, methotrexate, and 5-fluorouracil (CMF), a drug combination that is active in solid tumors, was evaluated using specific response criteria.. Fifty-two eligible patients with measurable (19), evaluable (29), or bone scan only (4) metastatic prostate cancer were treated with cyclophosphamide, 100 mg/m2 every day by mouth, methotrexate, 15 mg/m2 intravenously weekly, and 5-fluorouracil, 300 mg/m2 intravenously weekly. Treatment was given continuously unless interrupted by toxicity or disease progression.. There were two partial responses (7%) among the evaluable patients. Six (32%) measurable patients and four (14%) evaluable patients had stable disease. Median time to progression was 3.2 months for measurable and 2.8 months for evaluable disease patients. Median survivals were 10.9 and 10.2 months, respectively. There was no difference between the two groups with regard to response rate or survival. Toxicity was acceptable and consisted primarily of myelosuppression.. CMF is minimally active in hormone-refractory metastatic prostate cancer.

Topics: Acid Phosphatase; Adenocarcinoma; Aged; Alkaline Phosphatase; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Bone Neoplasms; Cyclophosphamide; Fluorouracil; Humans; Male; Methotrexate; Middle Aged; Prostatic Neoplasms; Remission Induction; Survival Rate

From March 1987 to December 1990, 373 patients with stage C and D prostate cancer were randomized to receive either goserelin acetate alone or goserelin acetate plus flutamide. At a median follow-up time of 24 months, there was no significant difference in the response rate, progression-free and overall survival between the two treatment groups. In particular, median time to progression was 18 months in the goserelin arm and 24 months in the combined treatment arm (P = 0.09). However, median time to progression in stage D patients was 12 months in both treatment groups. Median time to death was 32 and 34 months, respectively. The combination regimen produced a more rapid normalisation of prostatic acid phosphatase levels and a prompt relief of bone pain. However, significantly more patients in the combination arm experienced treatment-related side-effects such as diarrhoea and increases in transaminase levels. The concurrent use of goserelin acetate and flutamide does not seem to significantly improve the results that can be achieved with goserelin acetate alone.

Topics: Acid Phosphatase; Aged; Aged, 80 and over; Flutamide; Goserelin; Humans; Male; Middle Aged; Prostatic Neoplasms; Time Factors

A total of 28 untreated patients with asymptomatic, stage D prostate cancer was randomized in a double-blinded fashion to receive finasteride (10 mg. per day), a 5 alpha-reductase inhibitor or placebo. Patients were evaluated at 3-week intervals by rectal examination, and serum prostate specific antigen (PSA) and prostatic acid phosphatase (PAP) levels, and at 6-week intervals by bone scan and transrectal ultrasound determinations of prostatic volume. Patients stopped the medication at week 6 at the discretion of the investigator when PSA levels increased from baseline. After 12 weeks all patients were reevaluated. Of the patients 13 received finasteride and 15 received placebo. The 2 groups did not differ statistically with respect to patient age, initial PSA and PAP level, or the extent of metastases on initial bone scan. A statistically significant decrease in the median percentage change from baseline in PSA at weeks 3 and 6 occurred in the finasteride group compared to the placebo group (-22.9% versus -2.9% and -15.1% versus +11.7%, respectively, p less than 0.05). Finasteride had no effect upon PAP, serum testosterone, prostatic volume or appearance of bone scans. A decrease in serum PSA in the finasteride treatment group suggests that finasteride exerts a minor effect in patients with prostate cancer. This effect does not approach that seen with medical or surgical castration yet because of the potency preserving feature and the lack of toxicity finasteride may warrant further study in the treatment of prostate cancer.

Topics: 5-alpha Reductase Inhibitors; Acid Phosphatase; Aged; Aged, 80 and over; Androstenes; Azasteroids; Biomarkers, Tumor; Double-Blind Method; Finasteride; Humans; Male; Middle Aged; Neoplasm Staging; Prostate-Specific Antigen; Prostatic Neoplasms; Quality of Life

One hundred forty-two patients with progressive, hormonally refractory advanced prostate carcinoma who had not received prior chemotherapy were randomized to receive either combination chemotherapy with 5-fluorouracil (5-FU), doxorubicin, and mitomycin C (FAM) or sequential chemotherapy with the same agents, i.e., mitomycin C, followed by doxorubicin on disease progression, followed by 5-FU. Objective tumor regressions were observed in 10 of 70 (14%) patients receiving the FAM treatment arm and 10 of 72 (14%) patients initially receiving mitomycin C. Of the 24 patients who received secondary therapy with doxorubicin alone, 3 (12.5%) achieved objective tumor regression. There were no responses among five patients who received tertiary therapy with 5-FU alone. The median survival time for all patients treated with the combination arm was 8.7 months, compared with 7.1 months for patients who received the FAM arm (P = 0.025). However, this modest survival advantage in favor of the FAM treatment arm must be weighed against significantly more myelosuppression experienced by these patients. The chemotherapeutic regimens used in this study have only minor clinical value in the treatment of hormonally refractory advanced prostate cancer.

Topics: Acid Phosphatase; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma; Doxorubicin; Fluorouracil; Humans; Leukopenia; Male; Mitomycin; Prostatic Neoplasms; Remission Induction; Survival Rate; Thrombocytopenia

We report preliminary results for the first 164 patients enrolled in a multicenter study comparing the endocrine effects, efficacy, and safety of 3.6 mg of goserelin acetate (Zoladex) and orchiectomy in patients with Stage D2 prostate cancer. Eighty-one patients were randomly allocated to receive Zoladex and 83 to orchiectomy. The median follow-up time for all patients was two hundred ten days. Median serum levels of testosterone were reduced to castrate levels (less than 50 ng/dL) within four weeks in both groups and remained suppressed for up to sixty weeks. An objective response according to modified criteria of the National Prostatic Cancer Project was observed in 81 percent and 78 percent of patients in the Zoladex and orchiectomy groups, respectively. There were no statistically significant differences between treatment groups in the distributions of time to treatment failure or time to disease progression. The most commonly reported adverse events in both treatment groups were hot flashes, cancer-related pain, unspecified pain, and urinary symptoms. These results suggest that Zoladex may offer an alternative to orchiectomy in the treatment of advanced prostate cancer.

Topics: Acid Phosphatase; Adenocarcinoma; Aged; Aged, 80 and over; Buserelin; Follow-Up Studies; Goserelin; Humans; Male; Middle Aged; Neoplasm Staging; Orchiectomy; Prospective Studies; Prostatic Neoplasms; Testosterone

A multicenter, randomized double-blind study was carried out in 203 patients with metastatic prostate cancer, in order to compare the efficacy of complete suppression of androgens achieved with surgical castration and nilutamide (Anandron), 100 mg t.i.d. The combined therapy was well-tolerated by patients, and they noted a better relief of bone pain after six months than those in the control group. There was a greater number of favorable responses in the combined treatment group. In addition, despite a similar median progression-free actuarial rate, the combined treatment (nilutamide plus orchiectomy) offered an improved survival time over orchiectomy alone.

Topics: Acid Phosphatase; Androgen Antagonists; Combined Modality Therapy; Double-Blind Method; Humans; Imidazoles; Imidazolidines; Male; Orchiectomy; Pain; Prostatic Neoplasms; Survival Rate

Flutamide (250 mg. orally 3 times daily) yielded a subjective response in 5 of 25 fully evaluable patients with hormone-resistant prostatic cancer. Four additional patients had early progression. A 40% or greater decrease in the pre-treatment prostate specific antigen level was observed in 7 of 24 patients and this finding was correlated with improved survival. Toxicity was mainly gastrointestinal and resulted in permanent discontinuation of flutamide in 5 patients. Flutamide or similar antiandrogens may have a role in the management of hormone-resistant prostatic cancer when relief of subjective symptoms should be an important treatment goal together with improvement of survival. However, before the drug should be used routinely in the management of hormone-resistant prostatic cancer phase 3 studies must confirm its effectiveness, especially in comparison to less expensive drugs.

Topics: Acid Phosphatase; Aged; Antigens, Neoplasm; Biomarkers, Tumor; Drug Evaluation; Flutamide; Humans; Male; Prostate-Specific Antigen; Prostatic Neoplasms

A depot preparation of leuprorelin acetate was assessed in 52 patients with advanced prostatic cancer. Patients received 3.75 mg, or occasionally 7.5 mg, leuprorelin acetate depot subcutaneously every 28 +/- 3 days for up to 2 years. Following treatment, there was one complete remission and 29 partial remissions; in other patients the disease was stable and in five it was progressive, with an estimated median time to progression of 500 days. Significant improvement in performance status, micturition problems and general well-being were reported. Suppression of serum testosterone and luteinizing hormone concentrations was maximal after 28 days and castration levels were maintained for up to 96 weeks. Tumour flare occurred in 15 (29%) patients during the first week of therapy but only one event was serious; sweating and flushing also occurred occasionally during the study. Of all administrations, 97% were free from any adverse local effect, the remaining events being mild in severity. It is concluded that once-monthly administration of leuprorelin acetate depot is effective in the management of advanced prostatic cancer and has an acceptable side-effect profile.

Topics: Acid Phosphatase; Aged; Aged, 80 and over; Alkaline Phosphatase; Antineoplastic Agents; Calcium; Clinical Trials as Topic; Creatinine; Delayed-Action Preparations; Gonadotropin-Releasing Hormone; Hemoglobins; Humans; Leuprolide; Luteinizing Hormone; Male; Middle Aged; Multicenter Studies as Topic; Prolactin; Prostatic Neoplasms; Testosterone

A collaborative multicenter trial was conducted by 17 Italian groups to verify whether the so-called total androgen blockade obtained with luteinizing hormone releasing hormone (LHRH) analogs combined with antiandrogens is more effective than conventional monotherapy in the treatment of advanced prostatic cancer. A total of 328 previously untreated patients were evaluated: 163 patients received Zoladex depot alone, 3.6 mg subcutaneously every 28 days, and 165 patients received Zoladex depot plus cyproterone acetate (CPA), 200 mg/day orally. The follow-up period ranged from 41-251 weeks. Treatment was well tolerated, and side-effects in both groups mainly comprised loss of libido and erections, hot flashes and breast swelling and tenderness. There was no significant difference in objective response after 6, 12 and 24 months of treatment between the 2 groups. Median time to disease progression was comparable in both groups: 55 weeks in the Zoladex group and 54 weeks in the Zoladex plus CPA group. The time to disease progression and the survival distribution was comparable in both groups. Although there were no significant differences in the overall subjective response to both treatments, a faster improvement, with respect to pain and performance status was noted in the Zoladex plus CPA group (8 weeks) compared to Zoladex alone (12 weeks). The addition of antiandrogen, by inhibiting the initial elevation of plasma testosterone, may prevent the disease flare-up which occurs in a small number of patients during the first few days of treatment with LHRH analogs alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acid Phosphatase; Aged; Androgen Antagonists; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Buserelin; Cyproterone; Cyproterone Acetate; Follow-Up Studies; Gonadotropin-Releasing Hormone; Goserelin; Humans; Male; Prostatic Neoplasms; Testosterone

A statistical analysis of prognostic factors in 175 patients with hormonally treated disseminated prostatic cancer was done. The prognostic significance of performance status (PS), hemoglobin (Hb), alkaline phosphatase (Alk P), and testosterone was assessed with a univariate analysis. The authors did not find significant prognostic value in age, tumor size or grade, prostatic acid phosphatase, and prostate-specific antigen in these patients. In a multivariate logistic model (Cox regression), PS, Hb, and Alk P were found useful for dividing patients into prognostic groups. The prognosis for high-risk patients on standard hormonal treatment was very poor. The authors concluded that research on prognostic factors is useful and permits a division of patients into risk groups that makes choice of treatment more accurate. The use of new treatment combinations as a start treatment is appropriate for high-risk patients with disseminated prostatic cancer.

Topics: Acid Phosphatase; Aged; Aged, 80 and over; Alkaline Phosphatase; Androgen Antagonists; Antineoplastic Agents; Follow-Up Studies; Gonadotropin-Releasing Hormone; Humans; Imidazoles; Imidazolidines; Male; Middle Aged; Multicenter Studies as Topic; Prognosis; Prostate; Prostatic Neoplasms; Retrospective Studies; Risk Factors; Survival Rate; Testosterone

Topics: Acid Phosphatase; Alkaline Phosphatase; Antineoplastic Agents; Estramustine; Hormones; Humans; Male; Multivariate Analysis; Prognosis; Prostatic Neoplasms

Gonadotropin-releasing hormone (GnRH) analogues administered for the treatment of advanced prostatic cancer induce a transient increase in plasma testosterone levels during the first week of treatment, often with a secondary rise in plasma levels of prostatic acid phosphatase and a flareup of disease. To determine whether the antiandrogen nilutamide (Anandron) blocks these effects, we carried out a multicenter, placebo-controlled study of nilutamide in men with prostatic cancer treated with the GnRH analogue buserelin. Thirty-six men with disseminated prostatic cancer and elevated plasma levels of prostatic acid phosphatase were randomly assigned to two groups. Group 1 included 17 men who received buserelin (500 micrograms daily subcutaneously) and nilutamide (300 mg daily by mouth); group 2 included 19 men treated with buserelin and placebo. Symptoms were assessed, and plasma was collected before treatment, daily for 14 days, and on days 18, 22, and 29 after the initiation of treatment. Bone pain appeared or worsened in 5 of the 17 men in group 1 and in 12 of the 19 men in group 2 (P less than 0.05). Acute urinary obstruction occurred in one man in group 2. Despite similar changes in the plasma testosterone levels in both groups, the median concentration of plasma prostatic acid phosphatase decreased almost immediately in group 1, but increased transiently, then decreased on day 14 in group 2. Median levels of prostate-specific antigen decreased immediately in group 1 and decreased on day 8 in group 2. We conclude that nilutamide can prevent the adverse consequences of the buserelin-induced transient rise in plasma testosterone levels in men with advanced prostate cancer treated with a GnRH analogue.

Topics: Acid Phosphatase; Aged; Androgen Antagonists; Buserelin; Drug Evaluation; Humans; Imidazoles; Imidazolidines; Male; Multicenter Studies as Topic; Neoplasm Metastasis; Prostatic Neoplasms; Testosterone

Ketoconazole high dose (H.D.) effectively reduces the testosterone production in both adrenals and testes. Its use in the management of (metastatic) prostate cancer has been advocated. Even in relapsing patients, after previous hormonal therapy, ketoconazole H.D. could be of value. Twenty-eight relapsing patients, of whom 15 were evaluable at three months, have been treated with ketoconazole H.D. As could be expected, objective response was seen in only a small number of patients followed up till nine months. Subjective improvement, however, was noticed in the majority of symptomatic patients. The side effects and toxicity of the therapy remain a major limitation for the use of ketoconazole, be it as first line treatment or as therapy for relapsing patients.

Topics: Acid Phosphatase; Adenocarcinoma; Aged; Aged, 80 and over; Androgen Antagonists; Clinical Trials as Topic; Gastrointestinal Diseases; Humans; Hydrocortisone; Ketoconazole; Male; Middle Aged; Prostatic Neoplasms; Random Allocation; Testosterone

The serum levels of gamma-Seminoprotein (gamma-Sm) were determined by enzyme immunoassay in 77 patients with prostatic cancer (30 untreated and 47 treated), 44 patients with benign prostatic hypertrophy and 12 patients with prostatitis. Serum levels of gamma-Sm in each disease were as follows; untreated prostatic cancer 23.2 +/- 18.3 ng/ml (positive rate 93%), treated prostatic cancer 4.7 +/- 8.3 (positive rate 25.5%), benign prostatic hypertrophy 3.6 +/- 3.3 (positive rate 23.7%), prostatitis 2.0 +/- 2.0 (positive rate 7.7%). Serum gamma-Sm levels in prostatic cancer were higher in advanced stage but relatively low in poorly differentiated adenocarcinoma. We consider that the level of serum gamma-Sm is a useful tumor marker as well as prostatic acid phosphatase (PAP) in diagnosis and follow-up of the patients with prostatic cancer.

Topics: Acid Phosphatase; Adenocarcinoma; Biomarkers, Tumor; Blood Proteins; Humans; Immunoenzyme Techniques; Japan; Male; Multicenter Studies as Topic; Neoplasm Staging; Predictive Value of Tests; Prostate; Prostatic Hyperplasia; Prostatic Neoplasms; Prostatic Secretory Proteins; Prostatitis; Seminal Plasma Proteins

From April 1984 to May 1986, 129 patients with prostate cancer entered a prospective trial with a new LH-RH agonist, Zoladex. Mean age was 72 years (range of 45-94 years) and, in most cases, patients had metastatic disease, not previously treated by chemotherapy or hormone therapy. Patients received a monthly injection of 3.6 mg. Serum testosterone was lowered into the range of castrate levels after 4 weeks of treatment. In 105 evaluable patients at 3 months, a 65% partial response (PR) rate was observed, with 11% stable and 24% progressive disease. Median time to progression was 37 weeks. Analysis of objective criteria revealed 30% PR for prostate volume and 51% CR-PR for prostatic acid phosphatases. Seventeen percent of lytic metastases had recalcified. One hundred twenty-nine patients were evaluable for toxicity. Endocrinological side effects were common: decrease in libido, 92%; impotence, 86%; hot flushes, 48%; and breast swelling or tenderness, 9%. Nonendocrinologic side effects were rare. The treatment is generally well accepted by patients owing to the convenient depot formulation and to the minor side effects.

Topics: Acid Phosphatase; Aged; Aged, 80 and over; Buserelin; Delayed-Action Preparations; Follicle Stimulating Hormone; France; Goserelin; Humans; Injections, Subcutaneous; Luteinizing Hormone; Male; Middle Aged; Multicenter Studies as Topic; Neoplasm Metastasis; Neoplasms, Hormone-Dependent; Prospective Studies; Prostate; Prostatic Neoplasms

We conducted a randomized clinical trial in men with stage D2 prostate cancer to test whether androgen priming potentiates the efficacy of cytotoxic chemotherapy. Eighty-five men with progressive prostate cancer refractory to orchiectomy were treated continuously with aminoglutethimide and hydrocortisone to lower adrenal androgen secretion and were administered cyclic intravenous (IV) chemotherapy. The patients were randomized to receive either androgen priming or no additional treatment for three days before and on the day of chemotherapy. Median duration of follow-up was 43 months. Response rate (remission plus disease stabilization) was not significantly different between the stimulation and control arm when the analysis was restricted to evaluable patients (79% v 73%, respectively) or when it was extended to all patients (46% v 61%). Median duration of response was similar for the stimulation and control arm (9 and 10 months, respectively). Median survival was 10 months in the stimulation and 15 months in the control group (P = .0047). The androgen sensitivity of the tumors was supported by the greater toxicity in the stimulation arm associated with androgen administration. Factors found to be independently associated with improved clinical outcome included a high Karnofsky score and hematocrit, long duration of response to the initial castration, and normalization of an elevated serum acid phosphatase on treatment. We conclude that in this group of patients with advanced disease, androgen priming does not potentiate the efficacy of chemotherapy and is actually associated with a worse outcome. Furthermore, our data emphasize the heterogeneity of biologic behavior of prostate cancer.

Topics: Acid Phosphatase; Aged; Aminoglutethimide; Antineoplastic Combined Chemotherapy Protocols; Clinical Trials as Topic; Cyclophosphamide; Doxorubicin; Fluorouracil; Fluoxymesterone; Follow-Up Studies; Humans; Hydrocortisone; Male; Prostatic Neoplasms; Random Allocation; Testosterone; Time Factors

From 1982 to 1985, the National Prostatic Cancer Treatment Group conducted a randomized prospective trial of single-agent or combination chemotherapy in 180 patients with metastatic prostatic disease refractory to hormonal therapy. All three of the treatment regimens, methotrexate, Adriamycin plus cyclophosphamide, cis-platinum plus 5-fluorouracil plus cyclophosphamide, showed similar survival and progression-free survival intervals. Future studies utilizing these or other agents, in similar or modified dosage schedules or delivery mechanisms, should note these results. Protocols designed to address subjective quality of life measures and other benefit ratios can be effectively employed considering this report.

Topics: Acid Phosphatase; Alkaline Phosphatase; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Clinical Trials as Topic; Cyclophosphamide; Doxorubicin; Fluorouracil; Humans; Male; Methotrexate; Prostatic Neoplasms; Random Allocation

One hundred and thirty-nine patients with advanced prostate cancer were entered into a randomised trial to test the efficacy and tolerance of goserelin 3.6 mg depot (Zoladex) versus stilboestrol 3 mg/day. As well as the usual clinical and radiological assessments of extent of disease, we used an immunoradiometric assay of prostate specific antigen (PSA) (Hybritech Europe) and normal laboratory enzymatic assays of acid phosphatase (AP) and alkaline phosphatase (ALKP) for biochemical assessment. The upper limit of normal for PSA was taken as 10 micrograms/l. The range of PSA was wide and differed significantly from that of AP and to a lesser extent ALKP in metastatic cases. PSA outperformed both AP and ALKP in both the local and advanced groups in terms of sensitivity. There was no correlation, however, between histological grade and level of PSA, AP or ALKP (the latter in cases with bone disease). In patients with metastatic disease diagnosed by bone scan, nine patients had one abnormal site/one "hot spot", and all of these had a PSA greater than twice the normal upper limit. Early death due to prostate cancer was noted in four patients with levels of PSA greater than 2500 micrograms/l. PSA is more sensitive than either enzymatic AP or ALKP in both locally advanced and metastatic prostate cancer and is useful in identifying those advanced cases who have single lesions on bone scan. In this series PSA gave an overall sensitivity of 89%, compared with 63% for AP and 64% for ALKP in patients with metastatic disease.

Topics: Acid Phosphatase; Alkaline Phosphatase; Antigens, Neoplasm; Biomarkers, Tumor; Bone Neoplasms; Buserelin; Diethylstilbestrol; Goserelin; Humans; Male; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Random Allocation

Ninety-five patients with stage C (C1 + C2) or D (D1 + D2) prostatic carcinoma were treated with the depot formulation of D-TRP-6 LH-RH ("Decapeptyl") for up to 33 months. Serum testosterone (T) levels were significantly reduced to castration levels within 4 weeks and maintained persistently low. Similarly, LH levels were decreased, although they remained in the normal range. Stimulation tests with either Gn-RH or HCG in course of treatment showed the achievement of a complete pituitary desensitization and almost a complete down-regulation of testicular LH receptors. Of 88 patients evaluable for response, about one-half showed an objective response. In most cases, subjective improvement with relief of bone pain and/or urinary symptoms was obtained without major side effects. These results indicate that the depot formulation of D-TRP-6 LH-RH offers an effective therapeutic alternative for patients with advanced prostatic cancer.

Topics: Acid Phosphatase; Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Carcinoma; Clinical Trials as Topic; Delayed-Action Preparations; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Humans; Luteinizing Hormone; Male; Middle Aged; Prostatic Neoplasms; Testosterone; Triptorelin Pamoate

Topics: Acid Phosphatase; Aged; Androgen Antagonists; Antineoplastic Combined Chemotherapy Protocols; Buserelin; Clinical Trials as Topic; Double-Blind Method; Humans; Imidazoles; Imidazolidines; Male; Prostatic Neoplasms

Response criteria and the reporting of results in clinical trials on drug therapy of stage D prostate cancer were evaluated by examination of studies listed in the Index Medicus 1980-1984. During this 5-year period, 70 studies (51 phase II and 16 phase III) were listed, comprising 3184 evaluable patients. Among 346 patients reported as having evaluable disease according to the WHO criteria, 198 had well-defined evaluable disease. A variety of response criteria were used, the NPCP criteria being the most frequent. Only three studies included solely patients with evaluable disease according to the WHO criteria. Reporting of results was often inadequate. The value of the most frequently used response parameters such as acid phosphatase, bone scan, per-rectal ultrasound, CT scan, bone pain and performance status is discussed. A system to standardise the reporting of results is proposed.

Topics: Acid Phosphatase; Bone Neoplasms; Clinical Trials as Topic; Drug Evaluation; Humans; Liver Neoplasms; Male; Pain Management; Prognosis; Prostatic Neoplasms; Radiography; Radionuclide Imaging; Soft Tissue Neoplasms

A total of 566 evaluable patients were accessioned to a phase III RTOG study of extended field irradiation in carcinoma of the prostate from 1976 to 1983. Eligible patients were those with locally advanced disease, either clinical Stage C or clinical Stage A2 or B with pelvic lymph node involvement. The treatment consisted of irradiation of the regional lymphatics followed by a boost to the prostate. The data have been analyzed extensively to identify variables of potential prognostic significance. The assessed factors include tumor size, clinical stage, the degree of histological differentiation, nodal status, serum acid phosphatase status, hormonal management status, age, and race. These factors have been assessed as to their interdependence and correlation with the clinical course (study endpoints) using univariate analyses and Cox's Regression model. Significant interdependence of tumor size and Gleason score and tumor size and acid phosphatase was identified. The population receiving hormonal management either prior to or during radiotherapy had a significantly higher proportion of high grade tumors. Correlation of the assessed variables and the study endpoints (local control, incidence of distant metastases, NED survival, survival) singled out the degree of histological differentiation as the most powerful prognostic factor for all the endpoints. Age proved a useful predictor of local control (younger patients failed at a significantly higher rate), as did tumor size. Elevation of serum acid phosphatase correlated well with the incidence of metastatic disease but was not a useful predictor of survival. Tumor size and hormonal management status correlated well with the incidence of metastatic disease but only when analyzed separately from other factors. Their prognostic value was absent when Cox regression analysis was applied. Nodal status did not correlate well with any of the study endpoints, indicating then that in patients with clinical Stage C disease, treated with definitive radiotherapy to the prostate and regional lymphatics, this parameter may have limited prognostic usefulness. Although patients who received concomitant hormonal management had a significantly higher proportion of high grade lesions, their clinical course fared favorably in comparison with the population not receiving concomitant hormonal management. This may indicate a beneficial effect of adjuvant hormonal treatment which needs to be tested in a prospective study.

Topics: Acid Phosphatase; Estrogens; Humans; Male; Neoplasm Recurrence, Local; Orchiectomy; Prognosis; Prostatic Neoplasms

During an 8-year period, 1,065 serum specimens were collected from 79 patients with prostate cancer of stages B2 to D1 (group I) and 51 patients with newly diagnosed stage D2 prostate cancer (group II) to evaluate statistically the relative reliability of elevated tumor-associated markers for progressive disease in prostate cancer. Forty of the group I patients and 21 of the group II patients presented a clinical progression of disease during follow-up. With the use of Gail's modification of Cox's regression model, serial acid phosphatase (AcP), total alkaline phosphatase (TAP), bone alkaline phosphatase (BAP), prostatic acid phosphatase (PAP), and prostate-specific antigen (PA) were analyzed. Results from group I patients revealed that only PA (P = .0002) and PAP (P = .0684) were prognostically important markers for detection of imminent disease progression. However, all markers were prognostically important in group II patients. Comparative studies indicated that PA (P = .0052) and PAP (P = .0359) were the more reliable markers for group I patients, whereas PA (P less than .0001), BAP (P = .0007), and PAP (P = .0206) were the more reliable markers for group II patients. Multivariate analyses revealed that, after adjustment for the effect of PA, no other marker was significantly related to the risk of progression. Elevated PA levels were predictive of increased risk 6 months before disease progression in group I patients only (P less than .0001). Overall, the apparent order of prognostic reliability for disease progression was found to be PA greater than PAP greater than BAP greater than AcP greater than TAP.

Topics: Acid Phosphatase; Alkaline Phosphatase; Antigens, Neoplasm; Bone and Bones; Bone Neoplasms; Clinical Trials as Topic; Double-Blind Method; Humans; Male; Neoplasm Recurrence, Local; Neoplasm Staging; Prognosis; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Random Allocation; Risk; Time Factors

Chronic administration of a depot form of D-Trp6 luteinizing hormone-releasing hormone (LH-RH), an LH-RH analogue (3 mg i.m. every 28 days for a mean period of 9.1 months), to 14 patients with locally extended or metastatic cancer of the prostate provided a good degree of disease control. After a slight and transient increase in gonadotropin secretion, the peptide induced a sharp and long-lasting inhibition of both gonadotropin and testosterone secretion, contemporaneously with clinical improvement and without any important side effects. These results are comparable to those recorded by others after daily administration of LH-RH analogues.

Topics: Acid Phosphatase; Aged; Antineoplastic Agents; Bone Neoplasms; Clinical Trials as Topic; Delayed-Action Preparations; Gonadotropin-Releasing Hormone; Gonadotropins, Pituitary; Humans; Male; Prostate; Prostatic Neoplasms; Testosterone; Triptorelin Pamoate

In a randomized, prospective trial, 199 previously untreated patients with Stage D2 prostatic cancer were treated with 3 mg/day diethylstilbestrol (DES) or 1 mg/day leuprolide acetate, a luteinizing hormone releasing hormone analog. Both DES and leuprolide suppressed testosterone to the desired castrate levels. Objective measures of disease, such as acid phosphatase levels, and subjective measures, such as bone pain, performance status, and mobility, showed similar decreases in both groups. No progression of disease was seen in 86 per cent of the leuprolide-treated group, compared with 85 per cent of the DES-treated group. The time to disease progression, development of adverse reaction requiring discontinuation of treatment, or death was identical for the two groups. Hot flashes were more common with leuprolide than with DES. Gynecomastia and breast tenderness, nausea and vomiting, and peripheral edema occurred more often in the DES group. Of those taking DES, 13 per cent discontinued treatment because of side effects, compared with 3 per cent of those taking leuprolide.

Topics: Acid Phosphatase; Antineoplastic Agents; Clinical Trials as Topic; Diethylstilbestrol; Gonadotropin-Releasing Hormone; Hormones; Humans; Leuprolide; Male; Prospective Studies; Prostatic Neoplasms; Random Allocation; Testosterone

Eighty-seven previously untreated patients with clinical stage D2 (bone metastases) prostate cancer have received the combination therapy with a pure antiandrogen and an LHRH agonist (or orchiectomy) as first treatment in a multicentre study for up to 34 months (average = 16.2 months). A positive objective response assessed according to the criteria of the US NPCP has been observed in all cases. Pain disappeared in all patients within 1 month and performance become normal in all (including 2 bedridden patients) within 4 months. Progression of the disease after a period of remission has been observed in only 8 patients. Only one patient has died from prostate cancer while 3 have died from other causes. The probability of continuing response and survival at 2 years for the patients who receive the combination treatment (Kaplan-Meier's method) is 81 and 91%, respectively. By contrast, in the randomized group who had orchiectomy alone, 4 of 7 have died from prostate cancer (P less than 0.05 as compared to combination therapy). In addition to a marked improvement in the remission rate and survival, combination therapy maintains a good quality of life, hot flashes and a decrease or loss of libido being the only side-effects.

Topics: Acid Phosphatase; Anilides; Bone and Bones; Bone Neoplasms; Dehydroepiandrosterone; Dehydroepiandrosterone Sulfate; Drug Therapy, Combination; Flutamide; Gonadotropin-Releasing Hormone; Humans; Male; Orchiectomy; Prostatic Neoplasms; Radionuclide Imaging; Testosterone

In a controlled, prospective, randomized clinical trial, we evaluated the safety and efficacy of leuprolide, a superactive analog of luteinizing hormone releasing hormone, given in a single subcutaneous injection dose of 1 mg per day, versus diethylstilbestrol (DES) 3 mg per day by mouth in patients with previously untreated Stage D2 prostatic adenocarcinoma. Eleven leuprolide patients and 10 DES patients were evaluated for therapeutic response. Eighty per cent of patients in each group experienced subjective improvement in bone pain and urinary obstructive signs and symptoms. Although the pooled percentages of complete, partial, and stable objective responses were greater for the leuprolide group than the DES group, the sums of the percentages of complete and partial objective responses were comparable for both treatment groups during the first forty-eight and sixty weeks of the study, respectively. In addition, patients not responding to leuprolide generally experienced no benefit with crossover to DES, and vice versa. Serious adverse reactions were more common in the DES group and included fatal myocardial infarction, arrhythmia, deep venous thrombosis, and gynecomastia. Vasomotor flushing, disease flare, and injection site irritation occurred most often in leuprolide patients, but did not require modification or discontinuation of treatment.

Topics: Acid Phosphatase; Adenocarcinoma; Antineoplastic Agents; Clinical Trials as Topic; Diethylstilbestrol; Dihydrotestosterone; Gonadotropin-Releasing Hormone; Humans; Leuprolide; Male; Middle Aged; Neoplasm Staging; Prostate; Prostatic Neoplasms; Random Allocation; Testosterone; Time Factors

We compared the clinical efficacy and safety of Buserelin treatment versus orchiectomy in 29 patients with newly diagnosed advanced prostatic cancer. There was no significant difference between the two treatment modalities in 1) reduction of plasma testosterone to below 100 ng/dl after 8 weeks, 2) objective clinical response rates in patients with stage D2 carcinoma, 3) induction of complete remission in patients with stages C and D1 carcinoma, or 4) relapse rates and death rates in patients with stage D2 carcinoma. After scoring stage D2 disease according to our aggressiveness analysis system, we found that patients with less aggressive neoplasms displayed a qualitatively better response and more prolonged remission. These data and the absence of estrogenic effects confirm Buserelin as a favorable alternative to orchiectomy in the treatment of prostatic cancer. Additionally, the study demonstrates the importance of considering the heterogeneity of the aggressiveness of stage D2 disease in assessing the benefits of clinical trials in prostatic carcinoma.

Topics: Acid Phosphatase; Bone and Bones; Buserelin; Estradiol; Flushing; Follow-Up Studies; Humans; Male; Orchiectomy; Prostatic Neoplasms; Radionuclide Imaging; Testosterone; Ultrasonics

Response criteria for phase II and phase II trials of prostate carcinoma patients of the EORTC Genito Urinary-Group are described. These criteria, initially closely related to National Prostatic Cancer Project criteria, have gone through a development into the direction of more stringency. Admission of patients to phase II trials is now restricted to those showing objectively measurable lesions, excluding bone metastases. World Health Organization criteria are applied to these patients. For phase III trials, progression to Metastatic TNM system status, time to progression, and duration of survival are recommended as end points. Measurable marker lesions, as for phase II trials and subjective and nonspecific response criteria, are accepted as parameters for progression. Response usually is not evaluated in these studies. Based on recent literature and personal experiences, the author suggests that serum acid phosphatase (SPAP) and volume changes of the primary tumor can be used as indicators for response under certain conditions. There is obviously a great need for further development of objective response criteria for prostatic cancer patients.

Topics: Acid Phosphatase; Bone Neoplasms; Clinical Trials as Topic; Humans; Male; Prostate; Prostatic Neoplasms; Ultrasonography

Evaluation of response to systemic therapy in metastatic prostate cancer is often difficult because of the infrequency of nonbony indicator lesions. The authors previously described a set of response criteria for Phase II and III studies which can be applied in patients with only bony disease. They have retrospectively evaluated response to Adriamycin (doxorubicin) and (5-fluorouracil) 5-FU in 38 patients with measurable soft tissue and visceral disease, using their response criteria for acid phosphatase and clinical status and standard definitions of response. No correlation was attempted for bone disease. Agreement between the results obtained with each system was good. Using this system of evaluating response, patients with metastatic prostate cancer with bone-dominant disease are eligible for Phase II and III studies.

Topics: Acid Phosphatase; Aged; Bone Neoplasms; Clinical Trials as Topic; Doxorubicin; Drug Evaluation; Fluorouracil; Humans; Male; Middle Aged; Prognosis; Prostatic Neoplasms; Soft Tissue Neoplasms

Seventy-two patients with advanced prostatic carcinoma without previous endocrine therapy were treated with an oral nonsteroidal antiandrogen, flutamide. Sixty-three patients (87.5%) had a favorable response, and 9 patients showed no response. Flutamide appears to be a safe antiandrogen, usually effective in the management of patients with advanced prostatic cancer who have had no prior endocrine therapy.

Topics: Acid Phosphatase; Adenocarcinoma; Adult; Aged; Anilides; Bone Neoplasms; Clinical Trials as Topic; Flutamide; Humans; Hydronephrosis; Male; Middle Aged; Prostatic Neoplasms; Soft Tissue Neoplasms; Urination Disorders

Metastatic prostatic cancer can be present in a variety of different ways. The authors describe the differences among stages D-0, D-1, and D-2 disease and present the treatment options for each of the substages. They summarize and integrate the clinical evidence that bears on the potential efficacy of each treatment.

Topics: Acid Phosphatase; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Brachytherapy; Carcinoma; Castration; Clinical Trials as Topic; Combined Modality Therapy; Diethylstilbestrol; Estrogens; Gonadotropin-Releasing Hormone; Hormones; Humans; Leuprolide; Lymph Node Excision; Lymphatic Metastasis; Male; Neoplasm Staging; Prostatectomy; Prostatic Neoplasms; Radioisotope Teletherapy

We compared the efficacy and safety of the gonadotropin-releasing hormone analogue, leuprolide (1 mg subcutaneously daily), with diethylstilbestrol (DES, 3 mg by mouth daily) in patients with prostate cancer and distant metastases (Stage D2) who had not previously received systemic treatment. Initial therapy (leuprolide or DES) was continued for as long as an objective response was noted; cross-over to the alternative arm occurred at the time of disease progression or intolerable adverse reactions. Ninety-eight patients were randomly assigned to leuprolide, and 101 to DES. Suppression of testosterone and dihydrotestosterone and decreases in acid phosphatase were comparable in the two groups. Patients receiving DES experienced more frequent painful gynecomastia (P less than 0.00001), nausea and vomiting (P = 0.02), edema (P = 0.008), and thromboembolism (P = 0.065) than those receiving leuprolide. The leuprolide group reported more "hot flashes" (P = 0.00001). Overall, 86 per cent of the leuprolide group had an objective response (complete response, 1 per cent; partial response, 37 per cent; stable disease, 48 per cent), as compared with 85 per cent of the DES group (complete, 2 per cent; partial, 44 per cent; stable, 39 per cent). Actual survival rates at one year were 87 per cent for the leuprolide group and 78 per cent for the DES group (P = 0.17). We conclude that leuprolide offers an important alternative treatment that is therapeutically equivalent to and causes fewer side effects than DES for the initial systemic management of metastatic prostate cancer.

Topics: Acid Phosphatase; Adult; Aged; Antineoplastic Agents; Diethylstilbestrol; Drug Evaluation; Gonadotropin-Releasing Hormone; Hormones; Humans; Leuprolide; Male; Middle Aged; Neoplasm Metastasis; Prostatic Neoplasms; Random Allocation

Twenty-nine patients with advanced prostatic adenocarcinoma were evaluated clinically, biochemically and radiologically and randomly assigned either to orchiectomy or to medical treatment. The latter consisted of the chronic administration of an LHRH agonistic analogue by parenteral and/or intranasal routes. Plasma testosterone levels fell to castrate values and remained so for as long as the follow-up lasted (24 months); estrogen levels fell as well. No change in basal cortisol, thyroxine or prolactin levels was noticed. A decrease in prostate size and improvement in prostatism occurred in all. Bone pain and radiology conventionally or by isotopic scanning, did not parallel the improvement seen in the primary disease locus. Similarly, the changes in alkaline phosphatase were minimal when compared to that of prostatic acid phosphatase. Both enzymes increased prior to or concurrently with relapse of the disease. The longest remission and survival was seen in patients with low enzyme levels, non diffuse bone metastases and high degree of tumor differentiation. Chronic use of agonistic analogues of LHRH induces effective castration in men with prostatic carcinoma and can replace orchiectomy or estrogen administration. The quantitative analysis of androgen receptors (AR) in subcellular fractions of tumor cells; the use of techniques to enhance the number of AR in the cytosol; and the determination of the type II/I regulatory subunit of protein kinase may be used to identify hormone independent clones and spare patients of unnecessary procedures.

Topics: Acid Phosphatase; Adenocarcinoma; Alkaline Phosphatase; Bone and Bones; Buserelin; Hormones; Humans; Male; Neoplasm Staging; Orchiectomy; Prostate; Prostatic Neoplasms; Radiography; Receptors, Androgen; Ultrasonography

8 patients with advanced prostatic carcinoma were treated with the luteinising-hormone releasing-hormone agonist, ICI 118630, for up to 3 months. Patients received subcutaneous injections of ICI 118630 (either 100 micrograms or 250 micrograms daily). At the higher dose level, plasma testosterone concentrations were significantly reduced by day 14 and approximated to those previously recorded in castrated or diethylstilboestrol-treated patients. Plasma concentrations of luteinising hormone and follicle-stimulating hormone were similarly reduced. Reduction in the dose, to 100 micrograms/day, similarly reduced plasma testosterone. ICI 118630 shows considerable potential for the management of patients with advanced carcinoma of the prostate.

Topics: Acid Phosphatase; Gonadotropin-Releasing Hormone; Goserelin; Humans; Injections, Subcutaneous; Male; Prostatic Neoplasms; Testosterone

In patients with metastatic hormone-relapsed adenocarcinoma of the prostate, adriamycin was compared to 5-fluorouracil in a randomized trial in 99 patients and adriamycin alone was studied in an open trial in 48 patients. Response to adriamycin was superior as judged by response of measurable disease (25 vs 8%; P less than 0.05) and survival (median 29 vs 24 weeks; Cox analysis, P less than 0.03), but comparable as judged by acid phosphatase response. Ambulatory status and site of metastases influenced rate of response to chemotherapy. Activity level, site of metastases, weight loss, and the symptom of protein aversion were prognostic factors for survival. Hematologic and gastrointestinal toxicity were frequent but were tolerated satisfactorily. Adriamycin therapy may be beneficial in patients with prostatic cancer after hormone therapy.

Topics: Acid Phosphatase; Adenocarcinoma; Clinical Trials as Topic; Doxorubicin; Fluorouracil; Humans; Male; Prognosis; Prostatic Neoplasms

A controlled, randomized trial of estramustine phosphate versus stilbestrol has been conducted in patients with previously untreated adenocarcinoma of the prostate. Both drugs were equally effective in decreasing serum testosterone and acid phosphatase levels. No therapeutic advantage of estramustine over stilbestrol was noted. At 3 months, 50% of tumours treated with stilbestrol had regressed compared with 36% treated with estramustine, at 1 year the rates were 50% and 21% respectively and at 2 years 50% and 9%. However, there was no difference in objective stabilization and regression rates between the two groups or in therapeutic failure rates.

Topics: Acid Phosphatase; Adenocarcinoma; Aged; Clinical Trials as Topic; Diethylstilbestrol; Double-Blind Method; Estramustine; Follow-Up Studies; Humans; Male; Middle Aged; Neoplasm Metastasis; Nitrogen Mustard Compounds; Prolactin; Prostatic Neoplasms; Random Allocation; Testosterone

Topics: Acid Phosphatase; Antineoplastic Agents; Bone Neoplasms; Carcinoembryonic Antigen; Cisplatin; Clinical Trials as Topic; Creatine Kinase; Doxorubicin; Humans; Male; Prostatic Neoplasms

Experiences resulting from Emcyt therapy in patients with both newly diagnosed and hormone refractory advanced prostate cancer, as well as on adjuvant to surgery or radiotherapy in earlier disease are presented. Data from trials of the National Prostatic Cancer Project (NPCP) and a series from Roswell Park Memorial Institute (RPMI) were divided into short-term (up to twenty weeks and up to fifty-two weeks in adjuvant trials) and long-term therapy. Baseline disease and patient characteristics and toxicities encountered in these two treatment-duration groups were compared. Patients in a more favorable health or disease status and/or responded to therapy were more frequently in the long-term group. Patients in the long-term group tended to have higher over-all incidences of toxicity; and although many had occurrences begin as early as those in the short-term group, they were able to tolerate the therapy for relatively long periods. The agent is thus both effective and can be given safety for long periods of time.

Topics: Acid Phosphatase; Alkaline Phosphatase; Anorexia; Cardiovascular Diseases; Clinical Trials as Topic; Diarrhea; Drug Administration Schedule; Estramustine; Humans; Male; Nausea; Neoplasm Staging; Nitrogen Mustard Compounds; Probability; Prostatic Neoplasms; Time Factors; Vomiting

Topics: Acid Phosphatase; Adenocarcinoma; Clinical Trials as Topic; Humans; Male; Neoplasm Staging; Placebos; Prognosis; Prostatectomy; Prostatic Neoplasms; Random Allocation

This is the fifth completed randomized clinical trial of the National Prostatic Cancer Project. There were 125 patients with histologically confirmed relapsing clinical stage D prostatic cancer randomized to receive hydroxyurea, methyl-chloroethyl-cyclohexy-nitrosourea or cyclophosphamide. All patients had received and failed previous hormonal therapy. Patients whose disease progressed after 12 weeks on the initial therapy were crossed over or randomized to receive an alternate drug. There were 98 patients available for comparison of treatments. Objective responses included patients with complete or partial regression as well as stable disease. The response rates were 35 per cent for cyclophosphamide, 30 per cent for methyl-chloroethyl-cyclohexy-nitrosourea and 15 per cent for hydroxyurea. Subjective response parameters included improvement in performance status and relief of pain. Pain was improved in a fifth of the patients on each treatment area. Methyl-chloroethyl-cyclohexy-nitrosourea and hydroxyurea showed activity in advanced prostatic cancer patients but at the expense of excessive toxicity. Cyclophosphamide continues to be the most active single agent in this type of patient, particularly with regard to duration of response and survival. There was a statistically demonstrable advantage for cyclophosphamide over hydroxyurea and a marginal advantage over methyl-chloroethyl-cyclohexy-nitrosourea in survival experience.

Topics: Acid Phosphatase; Aged; Clinical Trials as Topic; Cyclophosphamide; Drug Administration Schedule; Humans; Hydroxyurea; Male; Middle Aged; Nitrosourea Compounds; Probability; Prognosis; Prostatic Neoplasms; Random Allocation; Semustine

Topics: Acid Phosphatase; Aged; Antineoplastic Agents; Clinical Trials as Topic; Drug Evaluation; Estramustine; Humans; Male; Middle Aged; Nitrogen Mustard Compounds; Prostatic Neoplasms; Testosterone

A number of chemotherapeutic agents show moderate promise for the palliative treatment of metastatic prostatic carcinoma. Although patterns of metastatic disease make classic response rates difficult to obtain and interpret, doxorubicin, cyclophosphamide, dacarbazine (DTIC), and cisplatin have activity in patients who have failed conventional hormonal treatment. In most studies, a survival advantage is seen for responders to these and other chemotherapeutic agents, but no survival advantage has been seen for the treatment cohorts when compared to groups not receiving chemotherapy. Therefore, estimates of the usefulness of these agents must be considered tentative. Multiple drug therapy has not yet shown definite superiority to single agent treatment. The uses and limitations of acid phosphatase as a tumor marker, as well as particular difficulties in measuring tumor response in the disease, are detailed herein.

Topics: Acid Phosphatase; Adenocarcinoma; Antineoplastic Agents; Cisplatin; Clinical Trials as Topic; Cyclophosphamide; Doxorubicin; Drug Therapy, Combination; Estramustine; Fluorouracil; Humans; Lomustine; Male; Prednimustine; Prostatic Neoplasms

Categories of objective response to chemotherapy for 460 advanced relapsing prostate cancer patients evaluated in the initial first four randomized clinical trials of the National Prostatic Cancer Project were compared by survival and other patient and disease characteristics. The response criteria for stable were shown to delineate patients with markedly improved survival and other disease conditions relative to those designated as progression. Survival was similar for stable and partial regression patients despite more frequent reduction of primary tumor and subjective improvement in performance status, pain, and body weight in the partial regression patients. Consequently, we feel that in these studies the stable category is valid and useful for determining efficacy of treatment in patients with advancing prostate cancer.

Topics: Acid Phosphatase; Antineoplastic Agents; Body Weight; Clinical Trials as Topic; Humans; Male; Neoplasm Recurrence, Local; Pain; Prognosis; Prostatic Neoplasms; Research Design; Risk

Eighty-eight patients with metastatic and hormonally unresponsive carcinoma of the prostate gland were treated with a multiagent chemotherapy protocol. Because of the difficulty in evaluating the response of patients to therapy, data were collected in a prospective fashion and analyzed for clinical or laboratory changes that correlated with improved survivorship. Decrease of initially abnormal values of either acid or alkaline phosphotase into the normal range was associated with prolonged survival; weight gain of more than 10% was also associated with improved survival. Thirty-three patients demonstrated a fall of acid or alkaline phosphatase into the normal range or they increased their weight by at least 10%. The median survival time for this group of patients was 76.1 weeks as compared to 28.2 weeks for patients who failed to exhibit these changes. In future studies of the treatment of metastatic prostate cancer, these changes might be used as criteria of response to therapy.

Topics: Acid Phosphatase; Aged; Alkaline Phosphatase; Antineoplastic Agents; Body Weight; Bone Marrow; Castration; Clinical Trials as Topic; Drug Therapy, Combination; Estradiol Congeners; Humans; Male; Middle Aged; Neoplasm Metastasis; Prostatic Neoplasms

The results of radiation therapy of patients with carcinoma of the prostate category T3-4NxMo are compared with those of the hormonal therapy and with those of hormonal therapy combined with external irradiation. The type of first indicators of existing or threatening metastases has been evaluated, their appearance after first treatment and the period between their appearance and the development of clinical metastases have been assessed. These data and perhaps the bone-marrow serum acid phosphatase levels prior to treatment might be helpful in the choice of treatment. As damage due to irradiation has become minimal, radiation therapy should be preferred in all patients prone to cardio-vascular accidents and in healthy men up to about 75 years.

Topics: Academies and Institutes; Acid Phosphatase; Age Factors; Aged; Bone Neoplasms; Humans; Male; Neoplasm Metastasis; Netherlands; Prostatic Neoplasms; Radiotherapy Dosage

Estramustine phosphate (Estracyt) was used in the treatment of 154 patients with carcinoma of the prostate in stage IV. Sixty-three patients were given Estracyt from the outset (primary treatment group) and 91 had previously received some other endocrine therapy (secondary treatment group). All of the patients were observed for more than one year. The drug was given intravenously and/or orally. Objective remissions occurred in 46 (73.0%) of the 63 patients in the primary treatment group and subjective remissions in all the objective responders and in 12 additional patients (92.0%). The corresponding figures for the secondary treatment group were 28 (30.7%) and 52 (57.1%) of 91. The side-effects were negligible, and the drug was well tolerated. No cumulative toxic effect was observed in patients who had been receiving the treatment for more than five years. In our opinion the compound is valuable in the treatment of advanced prostatic carcinoma (stage IV).

Topics: Acid Phosphatase; Administration, Oral; Clinical Trials as Topic; Drug Evaluation; Estramustine; Follow-Up Studies; Humans; Injections, Intravenous; Male; Nitrogen Mustard Compounds; Prostatic Neoplasms; Remission, Spontaneous

The design and details of a prospective, randomized study protocol involving bipedal lymphography, and exploratory laparotomy with selective node biopsy in patients with apparently localized adenocarcinoma of the prostate are presented. The analysis includes the results of selected diagnostic tests, and an assessment of the accuracy of clinical vs. surgical staging in 50 unselected patients. Lymphatic metastases were found at the time of diagnostic laparotomy in 18 of the 50 patients (36%). Both increasing size (advanced T stage) and decreasing differentiation of the primary tumor were associated with an increased incidence of lymph node metastases. Of 25 patients with T1 and T2 tumors (Stage B), and 25 patients with T3 tumors (Stage C), lymphatic dissemination was found in 20 and 52%, respectively. Eleven of 20 patients (55%) with poorly differentiated tumors had lymph node metastasis, compared with only 2 or 11 patients (18%) with well-differentiated tumors. Twelve patients had a change in their clinical stage following exploratory laparotomy; in eight the stage was increased and in four it was decreased. Of 18 patients with lymphatic metastases, some of which were extensive and most of which were associated with increased serum acid phosphatase values, no evidence of concurrent bony or visceral dissemination was found. Although preliminary, this finding should stimulate the search for effective treatment in these patients who were previously thought to be incurable on the basis of probable vascular dissemination.

Topics: Acid Phosphatase; Adenocarcinoma; Adult; Aged; Bone and Bones; Bone Marrow; Humans; Laparotomy; Lymphatic Metastasis; Lymphography; Male; Middle Aged; Prostatic Neoplasms; Radiotherapy, High-Energy

Plasma zinc concentrations rise in men over the age of 55 years and fall in women of a similar age-group. They are higher in men with clinically diagnosed benign prostatic hyperplasia, but the level does not appear to be related to the size of the gland. Plasma zinc concentrations are not helpful in the diagnosis or management of carcinoma of the prostate, but may prove useful in excluding this diagnosis.

Topics: Acid Phosphatase; Adult; Aged; Alkaline Phosphatase; Clinical Trials as Topic; Creatinine; Female; Humans; Male; Middle Aged; Neoplasm Metastasis; Organ Size; Prostate; Prostatic Hyperplasia; Prostatic Neoplasms; Urea; Zinc

Topics: Acid Phosphatase; Adult; Aged; Alkaline Phosphatase; Calcium; Clinical Trials as Topic; Humans; Male; Medroxyprogesterone; Middle Aged; Neoplasm Metastasis; Prostatic Neoplasms; Time Factors

Topics: Acid Phosphatase; Cardiovascular Diseases; Clinical Trials as Topic; Diethylstilbestrol; Follow-Up Studies; Humans; Male; Placebos; Prostatectomy; Prostatic Neoplasms; Testis; Time Factors

Topics: Acid Phosphatase; Adenocarcinoma; Administration, Oral; Castration; Clinical Trials as Topic; Diethylstilbestrol; Evaluation Studies as Topic; Humans; Male; Neoplasm Metastasis; Pain; Placebos; Prostatic Neoplasms; Time Factors; Ureteral Obstruction

Topics: Acid Phosphatase; Aged; Carcinoma; Cardiovascular Diseases; Cerebrovascular Disorders; Clinical Trials as Topic; Diethylstilbestrol; Electrocardiography; Heart Failure; Humans; Ischemia; Male; Myocardial Infarction; Neoplasm Metastasis; Placebos; Plasminogen; Prognosis; Prostate; Prostatic Neoplasms; Pulmonary Embolism

Topics: Acid Phosphatase; Carcinoma; Castration; Clinical Trials as Topic; Diethylstilbestrol; Humans; Lactose; Male; Neoplasm Metastasis; Palpation; Placebos; Progesterone; Prognosis; Prostatectomy; Prostatic Neoplasms

Approximately, 90% of men with advanced prostate cancer will develop bone metastasis. However, there have been few reports about noninvasive biomarker to detect and predict clinical outcome of bone metastasis (BM) in prostate cancer patients.. We examined 1127 patients who underwent prostate biopsy from August 2012 to June 2017. We also investigated bone turnover markers such as bone-specific alkaline phosphatase, type I collagen cross-linked N-terminal telopeptide, C-terminal pyridinoline cross-linked telopeptide of type I collagen, and tartrate-resistant acid phosphatase type 5b (TRACP 5b).. A total of 282 patients were diagnosed as prostate cancer with complete clinical data, and 34 patients with bone metastasis. Multivariate analysis revealed C-terminal pyridinoline cross-linked telopeptide of type I collagen, tartrate-resistant acid phosphatase type 5b, and prostate-specific antigen (PSA) were independent biomarkers in detection of BM (p < 0.05, respectively). Furthermore, we developed predictive model formula based on tartrate-resistant acid phosphatase type 5b and PSA, for which the area under the curve was 0.95. In patients with bone metastasis, multivariate cox proportional hazards analysis revealed that this model was significantly associated with poor clinical outcome of cancer-specific survival (p < 0.05). In validation cohort with 137 patients, we also confirmed the utility of this model for diagnosis of BM (the area under the curve = 0.95).. Our developed formula of tartrate-resistant acid phosphatase type 5b in accordance with PSA may serve as the useful tool in diagnosis and prediction of clinical outcome for prostate cancer with bone metastasis.

Topics: Acid Phosphatase; Biomarkers; Biomarkers, Tumor; Bone Neoplasms; Collagen Type I; Humans; Male; Prognosis; Prostate-Specific Antigen; Prostatic Neoplasms; Tartrate-Resistant Acid Phosphatase

PAP-FcK and PSA-FcK prostate cancer antigenic proteins transiently co-expressed in plant induce their specific humoral immune responses in mice. Prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP) have been considered as immunotherapeutic antigens for prostate cancer. The use of a single antigenic agent is unlikely to be effective in eliciting immunotherapeutic responses due to the heterogeneous and multifocal nature of prostate cancer. Thus, multiple antigens have been combined to enhance their anti-cancer effects. In the current study, PSA and PAP were fused to the crystallizable region (Fc region) of immunoglobulin G1 and tagged with KDEL, the endoplasmic reticulum (ER) retention signal motif, to generate PSA-FcK and PAP-FcK, respectively, and were transiently co-expressed in Nicotiana benthamiana. Western blot analysis confirmed the co-expression of PSA-FcK and PAP-FcK (PSA-FcK + PAP-FcK) with a 1:3 ratios in the co-infiltrated plants. PSA-FcK, PAP-FcK, and PSA-FcK + PAP-FcK proteins were successfully purified from N. benthamiana by protein A affinity chromatography. ELISA showed that anti-PAP and anti-PSA antibodies successfully detected PAP-FcK and PSA-FcK, respectively, and both detected PSA-FcK + PAP-FcK. Surface plasmon resonance (SPR) analysis confirmed the binding affinity of the plant-derived Fc fusion proteins to FcγRI/CD64. Furthermore, we also confirmed that mice injected with PSA-FcK + PAP-FcK produced both PSA- and PAP-specific IgGs, demonstrating their immunogenicity. This study suggested that the transient plant expression system can be applied to produce the dual-antigen Fc fusion protein (PSA-FcK + PAP-FcK) for prostate cancer immunotherapy.

Topics: Acid Phosphatase; Animals; Cancer Vaccines; Humans; Immunity; Male; Mice; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms

The role of human prostatic acid phosphatase (PAcP, P15309|PPAP_HUMAN) in prostate cancer was investigated using a new proteomics tool termed signal sequence swapping (replacement of domains from the native cleaved amino terminal signal sequence of secretory/membrane proteins with corresponding regions of functionally distinct signal sequence subtypes). This manipulation preferentially redirects proteins to different pathways of biogenesis at the endoplasmic reticulum (ER), magnifying normally difficult to detect subsets of the protein of interest. For PAcP, this technique reveals three forms identical in amino acid sequence but profoundly different in physiological functions, subcellular location, and biochemical properties. These three forms of PAcP can also occur with the wildtype PAcP signal sequence. Clinical specimens from patients with prostate cancer demonstrate that one form, termed PLPAcP, correlates with early prostate cancer. These findings confirm the analytical power of this method, implicate PLPAcP in prostate cancer pathogenesis, and suggest novel anticancer therapeutic strategies.

Topics: Acid Phosphatase; Androgens; Antineoplastic Agents, Hormonal; Biomarkers, Tumor; Cell Line, Tumor; Cell Proliferation; Drug Resistance, Neoplasm; Early Detection of Cancer; Endoplasmic Reticulum; Humans; Isoenzymes; Male; Predictive Value of Tests; Prostatic Neoplasms; Protein Conformation; Structure-Activity Relationship

Adenoid basal cell carcinoma (ABC) is considered a rare cervical neoplasm which when present in 'pure' form, uniquely amongst apparently malignant cervical tumours, has never been reported to metastasise or lead to fatal patient outcome. We recently encountered a case of ABC that was morphologically reminiscent of prostatic differentiation, more specifically basal cell hyperplasia of the prostate. Immunohistochemistry was strongly positive for the prostate related marker NKX3.1 in the glandular cells, but there was no expression of prostate specific antigen (PSA) or prostatic acid phosphatase (PAP). However, subsequent review of five additional cervical ABCs demonstrated focal PAP expression in two of four tested cases, and all were NKX3.1 positive. NKX3.1 expression was also demonstrated in the glandular epithelium of 10 additional gynaecological lesions considered to show prostatic differentiation including five cases of cervical ectopic prostatic tissue, three ovarian teratomas with prostatic differentiation, and two vaginal tubulosquamous polyps. We suggest that some lesions traditionally classified as ABC may in fact represent a variant of prostatic differentiation within the cervix, possibly analogous to basal cell hyperplasia of the prostate.

Topics: Acid Phosphatase; Aged; Biomarkers, Tumor; Carcinoma, Basal Cell; Cell Differentiation; Cervix Uteri; Female; Homeodomain Proteins; Humans; Hyperplasia; Immunohistochemistry; Male; Middle Aged; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Transcription Factors; Uterine Cervical Neoplasms

Transcriptomic landscape of prostate cancer (PCa) shows multidimensional variability, potentially arising from the cell-of-origin, reflected in serum markers, and most importantly related to drug sensitivities. For example, Aggressive Variant Prostate Cancer (AVPC) presents low PSA per tumor burden, and characterized by de novo resistance to androgen receptor signaling inhibitors (ARIs). Understanding PCa transcriptomic complexity can provide biological insight and therapeutic guidance. However, unsupervised clustering analysis is hindered by potential confounding factors such as stromal contamination and stress-related material degradation.. To focus on prostate epithelial cell-relevant heterogeneity, we defined 1,629 genes expressed by prostate epithelial cells by analyzing publicly available bulk and single- cell RNA sequencing data. Consensus clustering and CIBERSORT deconvolution were used for class discovery and proportion estimate analysis. The Cancer Genome Atlas Prostate Adenocarcinoma dataset served as a training set. The resulting clusters were analyzed in association with clinical, pathologic, and genomic characteristics and impact on survival. Serum markers PSA and PAP was analyzed to predict response to docetaxel chemotherapy in metastatic setting.. We identified two luminal subtypes and two aggressive variant subtypes of PCa: luminal A (Adipogenic/AR-active/PSA-high) (30.0%); luminal S (Secretory/PAP-high) (26.0%); AVPC-I (Immune-infiltrative) (14.7%), AVPC-M (Myc-active) (4.2%), and mixed (25.0%). AVPC-I and AVPC-M subtypes predicted to be resistant to ARI and have low PSA per tumor burden. Luminal A and AVPC-M predicted to be resistant to docetaxel and have high PSA/PAP Ratio. Metastatic PCa patients with high PSA/PAP ratio (>20) had significantly shorter progression-free survival than those with low ratio (≤20) following docetaxel chemotherapy.. We propose four prostate adenocarcinoma subtypes with distinct transcriptomic, genomic, and pathologic characteristics. PSA/PAP ratio in advanced cancer may aid in determining which patients would benefit from maximized androgen receptor inhibition or early use of antimicrotubule agents.

Topics: Acid Phosphatase; Adenocarcinoma; Antineoplastic Agents; Biomarkers, Tumor; Docetaxel; Epithelial Cells; Gene Expression Profiling; Genomics; Humans; Male; Neoplasm Grading; Prostate-Specific Antigen; Prostatic Neoplasms; Retrospective Studies; Sequence Analysis, RNA; Transcriptome

Recently, we have found that two urinary glycoproteins, prostatic acid phosphatase (ACPP) and clusterin (CLU), combined with serum prostate-specific antigen (PSA) can serve as a three-signature panel for detecting aggressive prostate cancer (PCa) based on a quantitative glycoproteomic study. To facilitate the translation of candidates into clinically applicable tests, robust and accurate targeted parallel reaction monitoring (PRM) assays that can be widely adopted in multiple labs were developed in this study. The developed PRM assays for the urinary glycopeptides, FLN*ESYK from ACPP and EDALN*ETR from CLU, demonstrated good repeatability and a sufficient working range covering three to four orders of magnitude, and their performance in differentiating aggressive PCa was assessed by the quantitative analysis of urine specimens collected from 69 nonaggressive (Gleason score = 6) and 73 aggressive (Gleason ≥ 8) PCa patients. When ACPP combined with CLU, the discrimination power was improved from an area under a curve (AUC) of 0.66 to 0.78. By combining ACPP, CLU, and serum PSA to form a three-signature panel, the AUC was further improved to 0.83 (sensitivity: 84.9%, specificity: 66.7%). Since the serum PSA test alone had an AUC of 0.68, our results demonstrated that the new urinary glycopeptide PRM assays can serve as an adjunct to the serum PSA test to achieve better predictive power toward aggressive PCa. In summary, our developed PRM assays for urinary glycopeptides were successfully applied to clinical PCa urine samples with a promising performance in aggressive PCa detection.

Topics: Acid Phosphatase; Biomarkers, Tumor; Clusterin; Glycoproteins; Humans; Male; Prostate-Specific Antigen; Prostatic Neoplasms

Low Temperature Plasma (LTP) generates reactive oxygen and nitrogen species, causing cell death, similarly to radiation. Radiation resistance results in tumour recurrence, however mechanisms of LTP resistance are unknown. LTP was applied to patient-derived prostate epithelial cells and gene expression assessed. A typical global oxidative response (AP-1 and Nrf2 signalling) was induced, whereas Notch signalling was activated exclusively in progenitor cells. Notch inhibition induced expression of prostatic acid phosphatase (PAP), a marker of prostate epithelial cell differentiation, whilst reducing colony forming ability and preventing tumour formation. Therefore, if LTP is to be progressed as a novel treatment for prostate cancer, combination treatments should be considered in the context of cellular heterogeneity and existence of cell type-specific resistance mechanisms.

Topics: Acid Phosphatase; Cell Death; Cell Differentiation; Cell Line, Tumor; Cell Proliferation; Epithelial Cells; Gene Expression Regulation, Neoplastic; Humans; Male; NF-E2-Related Factor 2; Plasma Gases; Prostate; Prostatic Neoplasms; Radiation Tolerance; Reactive Nitrogen Species; Reactive Oxygen Species; Receptors, Notch; Signal Transduction; Stem Cells; Transcription Factor AP-1

Prostate cancer is a candidate for immunotherapy because cancer cells express tissue-specific proteins that can be therapeutic targets. However, immune checkpoint inhibitors and active immunization have performed poorly in clinical trials. We developed a novel virus-like particle (VLP) vaccine composed of bovine papillomavirus L1 protein engineered to display surface docking sites. We decorated VLPs with peptides encoding T cell epitopes from two prostate cancer-associated tumor antigens, prostate stem cell antigen (PSCA), and prostatic acid phosphatase (PAP-1 and PAP-2), and a neo-antigen, stimulator of prostatic adenocarcinoma-specific T cells (SPAS-1). The VLP vaccines induced a mean frequency of antigen-specific IFN-γ secreting CD8 + T cells of 2.9% to PSCA, 9.5% to SPAS-1, 0.03% to PAP-1, and 0.03% to PAP-2 in tumor-bearing TRAMP mice. We treated TRAMP mice at 19-20 weeks of age, when mice have advanced stages of carcinogenesis, with either VLP vaccine, anti-PD1 antibody, or combination immunotherapy. The VLP vaccine alone or in combination with anti-PD1 antibody significantly reduced tumor burden, while anti-PD1 antibody had a modest non-significant therapeutic effect. All treatments significantly increased CD3 + and CD8 + T cell infiltration into tumor tissue compared to control mice, and combination therapy resulted in significantly greater CD3 + and CD8 + T cell infiltration than monotherapy. Reduction in tumor burden in vaccine-treated mice was inversely correlated with CD8 + T cell numbers in tumor tissue. No other immunotherapy has shown efficacy in this animal model of advanced prostate cancer, making bovine papillomavirus VLPs an attractive vaccine technology to test in patients with metastatic prostate cancer.

Topics: Acid Phosphatase; Animals; Antigens, Neoplasm; Cancer Vaccines; Capsid Proteins; CD8-Positive T-Lymphocytes; Disease Models, Animal; Epitopes, T-Lymphocyte; GPI-Linked Proteins; Humans; Interferon-gamma; Male; Mice, Transgenic; Neoplasm Proteins; Prostate-Specific Antigen; Prostatic Neoplasms; Treatment Outcome; Vaccination; Vaccines, Virus-Like Particle

Prostate cancer (PCa) is one of the most common cancer in men. Although hormone-sensitive PCa responds to androgen-deprivation, there are no effective therapies for castration-resistant PCa. It has been recently suggested that proton pump inhibitors (PPIs) may increase the risk of certain cancers; however, association with PCa remains elusive. Here, we evaluated the tumorigenic activities of PPIs in vitro, in PCa cell lines and epithelial cells from benign prostatic hyperplasia (BPH) and in vivo, in PCa mice xenografts. PPIs increased survival and proliferation, and inhibited apoptosis in LNCaP cells. These effects were attenuated or absent in androgen-insensitive DU-145 and PC3 cells, respectively. Specifically, omeprazole (OME) promoted cell cycle progression, increased c-Myc expression, ErbB2 activity and PSA secretion. Furthermore, OME induced the phosphorylation of MAPK-ERK1/2, PI3K/Akt and GSK-3β, and blunted the expression and activity of cellular prostatic acid phosphatase. OME also increased survival, proliferation and PSA levels in BPH cells. In vivo, OME promoted tumor growth in mice bearing LNCaP xenografts. Our results indicate that PPIs display tumorigenic activities in PCa cells, suggesting that their long-term administration in patients should be carefully monitored.

Topics: Acid Phosphatase; Animals; Apoptosis; Cell Proliferation; Glycogen Synthase Kinase 3 beta; Humans; Male; Mice, Inbred NOD; Mice, SCID; Mitogen-Activated Protein Kinase 1; Mitogen-Activated Protein Kinase 3; Neoplasms, Hormone-Dependent; Omeprazole; PC-3 Cells; Phosphatidylinositol 3-Kinase; Phosphorylation; Prostatic Neoplasms; Proto-Oncogene Proteins c-akt; Proton Pump Inhibitors; Receptor, ErbB-2; Signal Transduction

To characterize the disease progression and median survival of patients with prostate cancer (PCa) according to the prostatic-specific acid phosphatase (PAP) analysis in a population-based study from the Surveillance, Epidemiology, and End Results (SEER) database.. Prostate cancer patients with completed PAP results were identified using the SEER database of the National Cancer Institute. The Mann-Whitney Sum test was utilized to compare the statistical significance for measurement data and ranked data. Data were stratified by ages, races, TNM Classification of Malignant Tumors (TNM), pathological grades, number of tumors, PAP, and survival duration. Multivariable logistic analysis was performed to identify predictors of the presence of invasion and metastases. Cox regression was analyzed for the factors associated with all-cause mortality and prostate cancer-specific mortality. Moreover, survival curve was used to detect the survival months. The unknown data were excluded from these tests.. In total, there are 5184 PAP+ patients and 3161 PAP- patients involved. The Mann-Whitney Sum test showed that slightly greater tumor size (. The findings of this study provide population-based estimates of the PCa progress and prognosis for patients with different PAP results, which may suggest a renewed period for the PAP.

Topics: Acid Phosphatase; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Disease Progression; Humans; Male; Middle Aged; Neoplasm Metastasis; Prostatic Neoplasms

In this work, a novel sensor based on immobilised copper phthalocyanine, 2,9,16,23-tetracarboxylic acid-polyacrylamide (Cu(II)TC Pc-PAA) was developed for determination of acid phosphatase (ACP) levels in nanomolar quantities. Detection was based on the measurement of enzymatically generated phosphate, with initial studies focused on phosphate detection at a Cu(II)TC Pc-PAA modified screen-printed gold transducer. The sensor was characterised in relation to operational performance (pH, response time, stability, linearity, and sensitivity) and common anionic interferents (nitrate, sulphate, chloride, and perchlorate). The functionalised surface also facilitated rapid detection of the enzyme bi-product 2-naphthol over the range 5-3000 μM. Quantitation of ACP was demonstrated, realising a linear response range of 0.5-20 nM and LOD of 0.5 nM, which is within the clinical range for this prostate cancer biomarker.

Topics: Acid Phosphatase; Biomarkers, Tumor; Electrochemistry; Electrodes; Gold; Humans; Hydrogen-Ion Concentration; Indoles; Limit of Detection; Male; Organometallic Compounds; Perchlorates; Printing; Prostatic Neoplasms; Surface Properties; Time Factors; Transducers

This study aimed to radiolabel finasteride, a novel 5α-reductase inhibitor, to evaluate its cancer targeting potential in experimental model of prostate carcinogenesis. Finasteride was effectively radiolabeled with

Topics: Acid Phosphatase; Animals; Carcinogenesis; Carcinogens; Disease Models, Animal; Electrophoresis; Finasteride; Hydrogen-Ion Concentration; Kinetics; Male; Methylnitrosourea; Prostate; Prostatic Neoplasms; Radiopharmaceuticals; Rats; Rats, Sprague-Dawley; Technetium; Time Factors; Tissue Distribution

Prostate adenocarcinoma is the most common form of prostate cancer. We have previously shown in a murine model that prostatic acid phosphatase (PAP) deficiency leads to increased cell proliferation and development of prostate adenocarcinoma. The association between PAP and prostate cancer has been reported. Indeed, high PAP enzymatic activity is detected in the serum of patients with metastatic disease while its expression is reduced in prostate cancer tissue. However, the molecular mechanisms behind the onset of the disease remains poorly understood. We previously identified a novel transmembrane prostatic acid phosphatase (TMPAP) isoform, which interacts with snapin. TMPAP is expressed on the plasma membrane, as well as endosomal/lysosomal and exosomal membrane vesicles by means of a tyrosine-based lysosomal targeting motif (Yxxϕ).. We used stable overexpression of the secreted isoform (SPAP) and TMPAP in LNCaP cells, live cell imaging, microarray and qRT-PCR analyses, and fluid phase uptake of HRP and transferrin.. Our results indicate that the stable overexpression of TMPAP, but not SPAP in LNCaP cells reduces cell growth while increasing endo/exocytosis and cell size. Specifically, cells overexpressing TMPAP accumulate in the G1 phase of the cell cycle, and show altered gene expression profile.. Our data suggests that TMPAP may function as a non-canonical tumor suppressor by delaying cell growth in G1 phase of the cell cycle.

Topics: Acid Phosphatase; Cell Cycle; Cell Line, Tumor; Cell Membrane; Cell Proliferation; G1 Phase; Humans; Male; Prostatic Neoplasms

Management of bone metastasis remains clinically challenging and requires the identification of new molecular target(s) that can be therapeutically exploited to improve patient outcome. Galectin-3 (Gal-3) has been implicated as a secreted factor that alters the bone microenvironment. Proteolytic cleavage of Gal-3 may also contribute to malignant cellular behaviors, but has not been addressed in cancer metastasis. Here, we report that Gal-3 modulates the osteolytic bone tumor microenvironment in the presence of RANKL. Gal-3 was localized on the osteoclast cell surface, and its suppression by RNAi or a specific antagonist markedly inhibited osteoclast differentiation markers, including tartrate-resistant acid phosphatase, and reduced the number of mature osteoclasts. Structurally, the 158-175 amino acid sequence in the carbohydrate recognition domain (CRD) of Gal-3 was responsible for augmented osteoclastogenesis. During osteoclast maturation, Gal-3 interacted and colocalized with myosin-2A along the surface of cell-cell fusion. Pathologically, bone metastatic cancers expressed and released an intact form of Gal-3, mainly detected in breast cancer bone metastases, as well as a cleaved form, more abundant in prostate cancer bone metastases. Secreted intact Gal-3 interacted with myosin-2A, leading to osteoclastogenesis, whereas a shift to cleaved Gal-3 attenuated the enhancement in osteoclast differentiation. Thus, our studies demonstrate that Gal-3 shapes the bone tumor microenvironment through distinct roles contingent on its cleavage status, and highlight Gal-3 targeting through the CRD as a potential therapeutic strategy for mitigating osteolytic bone remodeling in the metastatic niche.

Topics: Acid Phosphatase; Animals; Bone and Bones; Bone Neoplasms; Bone Remodeling; Breast; Breast Neoplasms; Cell Communication; Cell Differentiation; Cell Line, Tumor; Female; Galectin 3; Humans; Isoenzymes; Male; Mice; Myosins; Neoplasm Metastasis; Osteoclasts; Prostatic Neoplasms; RANK Ligand; Tartrate-Resistant Acid Phosphatase

Bone metastases develop in several malignancies (multiple myeloma, breast, prostate and lung carcinoma) and cause several complications. The aim of this study was to search for new biomarkers to use in monitoring of bone metastatic disease with the use of xMAP technology.. We assessed 62 oncological patients: 23 with no bone metastases, 28 with metastatic disease not having undergone therapy and 11 with metastatic disease treated by denosumab. Serum levels of dickkopf-related protein 1 (DKK1), growth differentiation factor-15 (GDF15), neuron-specific enolase (NSE), osteoprotegerin (OPG), osteonectin, periostin, tartrate-resistant acid phosphatase (TRAP5), tumor necrosis factor related weak inducer of apoptosis (TWEAK), chitinase-3-like protein 1 (YKL40), carboxy-terminal telopeptide (CTX) and procollagen type 1 N-terminal propeptide (PINP) were measured in each sample.. The following biomarkers were observed to have significantly higher levels in the groups of patients with metastases in comparison to metastasis-free patients: GDF15 (p<0.0001), osteonectin (p=0.0311), TRAP5 (p<0.0046), TWEAK (p<0.0343) and YKL40 (p<0.0034). The changes in DKK1, NSE, OPG and periostin were not significant.. We identified five new biomarkers: GDF15, osteonectin, TRAP5, TWEAK, and YKL40 as being promising markers for monitoring bone metastases.

Topics: Acid Phosphatase; Adipokines; Aged; Aged, 80 and over; Biomarkers, Tumor; Bone Neoplasms; Breast Neoplasms; Chitinase-3-Like Protein 1; Colorectal Neoplasms; Cytokine TWEAK; Female; Growth Differentiation Factor 15; Humans; Isoenzymes; Lectins; Lung Neoplasms; Male; Middle Aged; Osteonectin; Pilot Projects; Prostatic Neoplasms; Tartrate-Resistant Acid Phosphatase; Tumor Necrosis Factors

Topics: Acid Phosphatase; Adenocarcinoma; Biomarkers, Tumor; Carcinoma, Squamous Cell; Histocytochemistry; Humans; Immunohistochemistry; Kallikreins; Male; Microscopy; Middle Aged; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Sarcoma; Tumor Suppressor Protein p53; Vimentin

XB130 is a cytosolic adaptor protein involved in various physiological processes and oncogenesis of certain malignancies, but its role in the development of prostate cancer remains unclear. In current study, we examined XB130 expression in prostate cancer tissues and found that XB130 expression was remarkably increased in prostate cancer tissues and significantly correlated with increased prostate specific antigen (PSA), free PSA (f-PSA), prostatic acid phosphatase (PAP) and T classification. Patients with highly expressed XB130 had significantly decreased survival, which suggested XB130 as a possible prognostic indicator for prostate cancer. In vitro experiments showed that reduced XB130 expression restrained tumor growth both in vitro and in vivo. Furthermore, XB130 knockdown hindered transition of G1 to S phase in prostate cancer cell line DU145 and LNCap, which might contribute to the inhibition of cellular proliferation. Results from transwell assay demonstrated that downregulation of XB130 may attenuate invasion and metastasis of prostate cancer. Semiquantitative analysis of Western blot suggested that decreased XB130 expression was accompanied by diminished Akt signaling and EMT process. Thus, above observations suggest that XB130 may be a novel molecular marker and potent therapeutic target for prostate cancer.

Topics: Acid Phosphatase; Adaptor Proteins, Signal Transducing; Biopsy; Carcinogenesis; Cell Growth Processes; Cell Line, Tumor; Gene Expression Regulation, Neoplastic; Humans; Male; Neoplasm Metastasis; Oncogene Protein v-akt; Prostate-Specific Antigen; Prostatic Neoplasms; RNA, Small Interfering; Signal Transduction; Up-Regulation

Prostate cancer (PCa) is unique in its tendency to produce osteoblastic (OB) bone metastases. There are no existing therapies that specifically target the OB phase that affects 90% of men with bone metastatic disease. Prostatic acid phosphatase (PAP) is secreted by PCa cells in OB metastases and increases OB growth, differentiation, and bone mineralization. The purpose of this study was to investigate whether PAP effects on OB bone metastases are mediated by autocrine and/or paracrine alterations in the receptor activator of nuclear factor κ-B (RANK)/RANK ligand (RANKL)/osteoprotegerin (OPG) system. To investigate whether PAP modulated these factors and altered the bone reaction, we knocked down PAP expression in VCaP cells and stably overexpressed PAP in PC3M cells, both derived from human PCa bone metastases. We show that knockdown of PAP in VCaP cells decreased OPG while increasing RANK/RANKL expression. Forced overexpression of PAP in PC3M cells had the inverse effect, increasing OPG while decreasing RANK/RANKL expression. Coculture of PCa cells with MC3T3 preosteoblasts also revealed a role for secretory PAP in OB-PCa cross talk. Reduced PAP expression in VCaP cells decreased MC3T3 proliferation and differentiation and reduced their OPG expression. PAP overexpression in PC3M cells altered the bone phenotype creating OB rather than osteolytic lesions in vivo using an intratibial model. These findings demonstrate that PAP secreted by PCa cells in OB bone metastases increases OPG and plays a critical role in the vicious cross talk between cancer and bone cells. These data suggest that inhibition of secretory PAP may be an effective strategy for PCa OB bone lesions.

Topics: Acid Phosphatase; Animals; Bone Neoplasms; Cell Differentiation; Cell Line, Tumor; Cell Proliferation; Humans; Male; Mice; Mice, SCID; Osteoblasts; Osteoprotegerin; Prostatic Neoplasms; RANK Ligand; RNA, Small Interfering; Signal Transduction

The addition of phosphate groups is an essential requirement for the proper functioning of cyclin and cyclin dependent kinase which control various stages in the mitotic division of cancer cells. Thus limiting the availability of phosphate is likely to interfere with the metabolism of rapidly growing malignant cells. The human hormone glucagon and the anti metabolite mithramycin reduce serum phosphate by increasing phosphaturia and are both very effective in treating Paget's disease of bone, a precancerous condition. In this disorder large doses of glucagon given intravenously relieve bone pain and cause serum phosphate and alkaline phosphatase as well as urine hydroxyproline to fall, indicating a marked reduction in bone turnover. A constant iv infusion of glucagon was given to each of three patients all of whom had secondary malignant bone deposits. Two of the patients had primary prostate cancer and one had a squamous cell lung tumour. All three patients had relief of bone pain and a fall in serum alkaline phosphatase. Serum acid phosphatase also fell in the two patients with prostate cancer. It is proposed that the marked drop in serum phosphate due to glucagon causes intracellular phosphate to fall. This in turn disrupts the addition and removal of phosphate groups essential for the proper functioning of cyclin and cyclin dependent kinase. These two proteins control the transition from G1 to S (DNA synthesis phase) and G2 to M (mitotic phase) in the dividing cycle of malignant cells. Depriving a tumour of an essential ingredient used in phosphorylation reactions will disrupt its growth. It is also proposed that, by the same mechanism, glucagon induced hypophosphataemia renders malignant cells more sensitive to established chemotherapeutic agents and radiation waves. If this hypothesis proves to be correct, lowering intracellular phosphate may become an useful tool in cancer therapy. However extensive studies are necessary to determine whether mitosis in cancer cells can be advantageously disrupted by glucagon induced hypophosphataemia.

Topics: Acid Phosphatase; Alkaline Phosphatase; Bone and Bones; Carcinoma, Squamous Cell; Glucagon; Humans; Hydroxyproline; Hypophosphatemia, Familial; Insulin; Lung Neoplasms; Male; Mitosis; Models, Theoretical; Neoplasms; Osteitis Deformans; Phosphates; Phosphorylation; Prostatic Neoplasms

Prostatic acid phosphatase (PAP) expression increases proportionally with prostate cancer progression, making it useful in prognosticating intermediate to high-risk prostate cancers. A novel ligand that can specifically bind to PAP would be very helpful for guiding prostate cancer therapy. RNA aptamers bind to target molecules with high specificity and have key advantages such as low immunogenicity and easy synthesis. Here, human PAP-specific aptamers were screened from a 2'-fluoropyrimidine (FY)-modified RNA library by SELEX. The candidate aptamer families were identified within six rounds followed by analysis of their sequences and PAP-specific binding. A gel shift assay was used to identify PAP binding aptamers and the 6N aptamer specifically bound to PAP with a Kd value of 118 nM. RT-PCR and fluorescence labeling analyses revealed that the 6N aptamer bound to PAP-positive mammalian cells, such as PC-3 and LNCaP. IMR-90 negative control cells did not bind the 6N aptamer. Systematic minimization analyses revealed that 50 nucleotide sequences and their two hairpin structures in the 6N 2'-FY RNA aptamer were equally important for PAP binding. Renewed interest in PAP combined with the versatility of RNA aptamers, including conjugation of anti-cancer drugs and nano-imaging probes, could open up a new route for early theragnosis of prostate cancer.

Topics: Acid Phosphatase; Aptamers, Nucleotide; Binding Sites; Cell Line, Tumor; Drug Screening Assays, Antitumor; Humans; Male; Models, Molecular; Prostatic Neoplasms; SELEX Aptamer Technique

In this paper, we developed a near-infrared mercaptopropionic acid (MPA)-capped CuInS2 quantum dot (QD) fluorescence probe for the detection of acid phosphatases (ACP), which is an important biomarker and indicator of prostate cancer. The fluorescence of CuInS2 QDs could be quenched by Cu(2+), and then the addition of adenosine-5'-triphosphate (ATP) could effectively turn on the quenched fluorescence due to the strong interaction between Cu(2+) and ATP. The ACP could catalyze the hydrolysis of ATP, which would disassemble the complex of Cu(2+)-ATP. Therefore, the recovered fluorescence could be quenched again by the addition of ACP. In our method, the limit of detection (LOD) is considerably low for ACP detection in solution. Using the CuInS2 QDs fluorescence probe, we successfully performed in vitro imaging of human prostate cancer cells.

Topics: Acid Phosphatase; Adenosine Triphosphate; Copper; Fluorescence; Fluorescent Dyes; Humans; Indium; Limit of Detection; Male; Prostatic Neoplasms; Quantum Dots; Spectrometry, Fluorescence; Spectroscopy, Near-Infrared; Sulfides; Tumor Cells, Cultured

Immunotherapy is one of the attractive treatment strategies for advanced prostate cancer. The US Food and Drug Administration (FDA) previously approved the therapeutic vaccine, sipuleucel-T, which is composed of autologous antigen-presenting cells cultured with a fusion protein [prostatic acid phosphatase (PAP) and granulocyte-macrophage colony-stimulating factor (GMCSF)]. Although sipuleucel-T has been shown to prolong the median survival of patients for 4.1 months, more robust therapeutic effects may be expected by modifying the vaccination protocol. In the present study, we aimed to develop and validate a novel vaccination strategy using multiple PAP-fused cytokines for prostate cancer treatment. Using a super gene expression (SGE) system that we previously established to amplify the production of a recombinant protein, significant amounts of PAP-fused cytokines [human GMCSF, interleukin-2 (IL2), IL4, IL7 and mouse GMCSF and IL4] were obtained. We examined the activity of the fusion proteins in vitro to validate their cytokine functions. A significant upregulation of dendritic cell differentiation from monocytes was achieved by PAP-GMCSF when used with the other PAP-fused cytokines. The PAP-fused human IL2 significantly increased the proliferation of lymphocytes, as determined by flow cytometry. We also investigated the in vivo therapeutic effects of multiple PAP-fused cytokines in a mouse prostate cancer model bearing prostate-specific antigen (PSA)- and PAP-expressing tumors. The simultaneous intraperitoneal administration of PAP-GMCSF, -IL2, -IL4 and -IL7 significantly prevented tumor induction and inhibited the tumor growth in the PAP-expressing tumors, yet not in the PSA-expressing tumors. The in vivo therapeutic effects with the multiple PAP-fused cytokines were superior to the effects of PAP-GMCSF alone. We thus demonstrated the advantages of the combined use of multiple PAP-fused cytokines including PAP-GMCSF, and propose a promising prostatic antigen-vaccination strategy to enhance the therapeutic effects.

Topics: Acid Phosphatase; Adenocarcinoma; Animals; Antigens, Neoplasm; Cancer Vaccines; Cell Differentiation; Cells, Cultured; Dendritic Cells; Drug Screening Assays, Antitumor; Drug Synergism; Gene Expression; Genes, Synthetic; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Immunotherapy, Active; Interleukins; Lymphocyte Activation; Male; Mice; Mice, Inbred C57BL; Monocytes; Plasmids; Prostatic Neoplasms; Recombinant Fusion Proteins

Approximately 90 % of patients who die of prostate cancer (PCa) have bone metastases, often promoting osteoblastic lesions. We observed that 88 % of castration-resistant PCa (CRPC) bone metastases express prostatic acid phosphatase (PAP), a soluble secreted protein expressed by prostate epithelial cells in predominately osteoblastic (n = 18) or osteolytic (n = 15) lesions. Additionally, conditioned media (CM) of an osteoblastic PCa xenograft LuCaP 23.1 contained significant levels of PAP and promoted mineralization in mouse and human calvaria-derived cells (MC3T3-E1 and HCO). To demonstrate that PAP promotes mineralization, we stimulated MC3T3-E1 cells with PAP and observed increased mineralization, which could be blocked with the specific PAP inhibitor, phosphonic acid. Furthermore, the mineralization promoted by LuCaP 23.1 CM was also blocked by phosphonic acid, suggesting PAP is responsible for the mineralization promoting activity of LuCaP 23.1. In addition, gene expression arrays comparing osteoblastic to osteolytic CRPC (n = 14) identified betacellulin (BTC) as a gene upregulated during the osteoblastic response in osteoblasts during new bone formation. Moreover, BTC levels were increased in bone marrow stromal cells in response to LuCaP 23.1 CM in vitro. Because new bone formation does occur in osteoblastic and can occur in osteolytic CRPC bone metastases, we confirmed by immunohistochemistry (n = 36) that BTC was highly expressed in osteoblasts involved in new bone formation occurring in both osteoblastic and osteolytic sites. These studies suggest a role for PAP in promoting the osteoblastic reaction in CRPC bone metastases and identify BTC as a novel downstream protein expressed in osteoblasts during new bone formation.

Topics: Acid Phosphatase; Bone and Bones; Bone Neoplasms; Cell Line, Tumor; Humans; Male; Mass Spectrometry; Osteoblasts; Prostatic Neoplasms; Protein Tyrosine Phosphatases; Reverse Transcriptase Polymerase Chain Reaction; Tumor Microenvironment

Treatment options for patients with advanced prostate cancer remain limited and rarely curative. Prostatic acid phosphatase (PAP) is a prostate-specific protein overexpressed in 95% of prostate tumours. An FDA-approved vaccine for the treatment of advanced prostate disease, PROVENGE® (sipuleucel-T), has been shown to prolong survival, however the precise sequence of the PAP protein responsible for the outcome is unknown. As the PAP antigen is one of the very few prostate-specific antigens for which there is a rodent equivalent with high homology, preclinical studies using PAP have the potential to be directly relevant to clinical setting. Here, we show three PAP epitopes naturally processed and presented in the context of HHDII/DR1 (114-128, 299-313, and 230-244). The PAP-114-128 epitope elicits CD4(+) and CD8(+) T-cell-specific responses in C57BL/6 mice. Furthermore, when immunised in a DNA vector format (ImmunoBody®), PAP-114-128 prevents and reduces the growth of transgenic adenocarcinoma of mouse prostate-C1 prostate cancer cell-derived tumours in both prophylactic and therapeutic settings. This anti-tumour effect is associated with infiltration of CD8(+) tumour-infiltrating lymphocytes and the generation of high avidity T cells secreting elevated levels of IFN-γ. PAP-114-128 therefore appears to be a highly relevant peptide on which to base vaccines for the treatment of prostate cancer.

Topics: Acid Phosphatase; Adenocarcinoma; Amino Acid Sequence; Animals; Antigens, Neoplasm; Cancer Vaccines; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Cell Line, Tumor; Epitopes, T-Lymphocyte; Flow Cytometry; Humans; Interferon-gamma; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Peptides; Prostate; Prostatic Neoplasms; T-Lymphocytes; Vaccination; Vaccines, Subunit

Prostate cancer cell lines have been used in the search for biomarkers that are suitable for prostate cancer diagnosis. Unfortunately, many cell line studies have only involved single cell lines, partially characterized cell lines or were performed without controls, and this may have been detrimental to effective biomarker discovery. We have analyzed a panel of prostate cancer and nonmalignant control cell lines using current biomarkers and then investigated a set of prospective endosomal and lysosomal proteins to search for new biomarkers.. Western blotting was used to define the amount of protein and specific molecular forms in cell extracts and culture media from a panel of nonmalignant (RWPE-1, PNT1a, PNT2) and prostate cancer (22RV1, CaHPV10, DU-145, LNCaP) cell lines. Gene expression was determined by qRT-PCR.. HPV-18 transfected cell lines displayed a different pattern of protein and gene expression when compared to the other cell lines examined, suggesting that these cell lines may not be the most optimal for prostate cancer biomarker discovery. There was an increased amount of prostatic acid phosphatase and kallikrein proteins in LNCaP cell extracts and culture media, but variable amounts of these proteins in other prostate cancer cell lines. There were minimal differences in the amounts of lysosomal proteins detected in prostate cancer cells and culture media, but two endosomal proteins, cathepsin B and acid ceramidase, had increased gene and protein expression, and certain molecular forms showed increased secretion from prostate cancer cells (P ≤ 0.05). LIMP-2 gene and protein expression was significantly increased in prostate cancer compared to nonmalignant cell lines (P ≤ 0.05).. While the existing prostate cancer biomarkers and lysosomal proteins investigated here were not able to specifically differentiate between a panel of nonmalignant and prostate cancer cell lines, endosomal proteins showed some discriminatory capacity. LIMP-2 is a critical regulator of endosome biogenesis and the increased expression observed in prostate cancer cells indicated that other endosome related proteins may also be upregulated and could be investigated as novel biomarkers.

Topics: Acid Phosphatase; Biomarkers, Tumor; Cell Line, Tumor; Humans; Kallikreins; Male; Prostate; Prostatic Neoplasms; Protein Tyrosine Phosphatases

Fowlpox virus (FPV) is a double-stranded DNA virus with a history of use as a live attenuated vaccine in commercial poultry production systems. FPV is also highly amenable to genetic engineering, with a large cloning capacity and many nonessential sites available for integration, meaning that in recombinant form, several transgenes can be expressed simultaneously. Recombinant FPV has proven an effective prophylactic vaccine vector for other diseases of birds, as well as other animal species (Brun et al., Vaccine 26:6508-6528, 2008). These vectors do not integrate into the host genome nor do they undergo productive replication in mammalian cells; thus they have a proven and impeccable safety profile and have been progressed as prophylactic and therapeutic vaccine vectors for use in humans (Beukema et al., Expert Rev Vaccines 5:565-577, 2006; Lousberg et al., Expert Rev Vaccines 10:1435-1449, 2011). Furthermore, repeated immunization with FPV does not blunt subsequent vaccine responses, presumably because it is replication-defective, and thus larger doses can be routinely administered (Brun et al., Vaccine 26:6508-6528, 2008). This strengthens the case for FPV as a viable platform vaccine vector, as it means it can be used repeatedly in an individual to achieve different immunological outcomes. Here we describe in detail the construction of a recombinant variant of FPV expressing the prostate tumor-associated antigen prostatic acid phosphatase (PAP) in conjunction with the immunostimulatory cytokine, interleukin-2 (IL-2), which, if undertaken under the appropriate regulatory conditions and with approvals in place, would theoretically be amenable to clinical trial applications.

Topics: Acid Phosphatase; Animals; Antigens, Neoplasm; Chick Embryo; DNA, Recombinant; Fibroblasts; Fowlpox virus; Genetic Engineering; Genetic Vectors; Homologous Recombination; Humans; Interleukin-2; Male; Prostatic Neoplasms; Protein Tyrosine Phosphatases; Rats; Transfection

Protein glycosylation is a common posttranslational modification and glycan structural changes have been observed in several malignancies including prostate cancer. We hypothesized that altered glycosylation could be related to differences in gene expression levels of glycoprotein synthetic enzymes between normal and malignant prostate tissues.. We interrogated prostate cancer gene expression data for reproducible changes in expression of glycoprotein synthetic enzymes. Over-expression of GCNT1 was validated in prostate samples using RT-PCR. ELISA was used to measure core 2 O-linked glycan sialyl Lewis X (sLe(x) ) of prostate specific antigen (PSA), Mucin1 (MUC1), and prostatic acidic phosphatase (PAP) proteins.. A key glycosyltransferase, GCNT1, was consistently over-expressed in several prostate cancer gene expression datasets. RT-PCR confirmed increased transcript levels in cancer samples compared to normal prostate tissue in fresh-frozen prostate tissue samples. ELISA using PSA, PAP, and MUC1 capture antibodies and a specific core 2 O-linked sLe(x) detection antibody demonstrated elevation of this glycan structure in cancer compared to normal tissues for MUC1 (P = 0.01), PSA (P = 0.03) and near significant differences in PAP sLe(x) levels (P = 0.06). MUC1, PSA and PAP protein levels alone were not significantly different between paired normal and malignant prostate samples.. GCNT1 is over-expressed in prostate cancer and is associated with higher levels of core 2 O-sLe(x) in PSA, PAP and MUC1 proteins. Alterations of O-linked glycosylation could be important in prostate cancer biology and could provide a new avenue for development of prostate cancer specific glycoprotein biomarkers.

Topics: Acid Phosphatase; Aged; Glycosylation; Humans; Lewis X Antigen; Male; Middle Aged; Mucin-1; N-Acetylglucosaminyltransferases; Prostate-Specific Antigen; Prostatic Neoplasms; Protein Tyrosine Phosphatases; Sialyl Lewis X Antigen

For stratified 2 × 2 tables, standard approximate confidence limits can perform poorly from a strict frequentist perspective, even for moderate-sized samples, yet they are routinely used. In this paper, I show how to use importance sampling to compute highly accurate limits in reasonable time. The methodology is very general and simple to implement, and orders of magnitude are faster than existing alternatives.

Topics: Acid Phosphatase; Age Factors; Aged; Clinical Trials as Topic; Computer Simulation; Confidence Intervals; Data Interpretation, Statistical; Humans; Lymph Nodes; Male; Middle Aged; Prostatic Neoplasms

Tumor markers (TMs) play an important role in clinical rapid screening and diagnosis for prostate cancer (PCa). In this study, we describe a competitive method to establish the multiplex suspension array by tumor biomarkers coated on distinguishable microbeads which competing with free biomarkers for their complementary antibodies (Ab) in one single reaction system for simultaneous and combined detection of prostate TMs in human serum. The volumes of the targets coupled onto the beads and their complementary Abs were optimized. The suspension array standard curves correlated well with PCa biomarkers (R(2)>0.9968). PCa biomarker levels were quantified using median fluorescent intensities. The working ranges of prostate-specific antigen (PSA), prostate stem cell antigen (PSCA), prostate-specific membrane antigen (PSMA) and prostatic acid phosphatase (PAP) were 0.47-502.94, 1.00-923.35, 1.00-524.79, and 1.73-176.07ngmL(-1) in serum samples, respectively. This method was compared to indirect competitive enzyme linked immunosorbent assay. It was found that high concordance between the two technologies resulted from serum samples of the eight PCa patients. The multiplex suspension array technology is specific to PCa biomarkers, displayed no significant cross-reactivity, and remains stable for 6 months. We also characterized the bead surface microstructures under different conditions employing a field emission scanning electron microscope. The suspension array is a straightforward and reliable method for analysis of multiple TMs with simple operation, high sensitivity at a low cost.

Topics: Acid Phosphatase; Antibodies; Antigens, Surface; Biomarkers, Tumor; Biosensing Techniques; Glutamate Carboxypeptidase II; Humans; Male; Membrane Proteins; Prostate-Specific Antigen; Prostatic Neoplasms

The molecular mechanisms underlying prostate carcinogenesis are poorly understood. Prostatic acid phosphatase (PAP), a prostatic epithelial secretion marker, has been linked to prostate cancer since the 1930's. However, the contribution of PAP to the disease remains controversial. We have previously cloned and described two isoforms of this protein, a secretory (sPAP) and a transmembrane type-I (TMPAP). The goal in this work was to understand the physiological function of TMPAP in the prostate. We conducted histological, ultra-structural and genome-wide analyses of the prostate of our PAP-deficient mouse model (PAP(-/-)) with C57BL/6J background. The PAP(-/-) mouse prostate showed the development of slow-growing non-metastatic prostate adenocarcinoma. In order to find out the mechanism behind, we identified PAP-interacting proteins byyeast two-hybrid assays and a clear result was obtained for the interaction of PAP with snapin, a SNARE-associated protein which binds Snap25 facilitating the vesicular membrane fusion process. We confirmed this interaction by co-localization studies in TMPAP-transfected LNCaP cells (TMPAP/LNCaP cells) and in vivo FRET analyses in transient transfected LNCaP cells. The differential gene expression analyses revealed the dysregulation of the same genes known to be related to synaptic vesicular traffic. Both TMPAP and snapin were detected in isolated exosomes. Our results suggest that TMPAP is involved in endo-/exocytosis and disturbed vesicular traffic is a hallmark of prostate adenocarcinoma.

Topics: Acid Phosphatase; Adenocarcinoma; Animals; Cell Line, Tumor; Cell Transformation, Neoplastic; Disease Models, Animal; Male; Mice; Mice, Knockout; Models, Biological; Prostate; Prostatic Neoplasms; Protein Binding; Protein Transport; Protein Tyrosine Phosphatases; Pseudopodia; Vesicular Transport Proteins

Prostate cancer (PCa) is the most commonly diagnosed type of cancer in men in western industrialized countries. As a public health burden, the need for the invention of new cost-saving PCa immunotherapies is apparent. In this study, we present a DNA vaccine encoding for the prostate-specific antigen prostatic acid phosphatase (PAP) linked to the J-domain and the SV40 enhancer sequence. The PAP DNA vaccine induced a strong PAP-specific cellular immune response after electroporation (EP)-based delivery in C57BL/6 mice. Splenocytes from mice immunized with PAP recognized the naturally processed PAP epitopes, indicating that vaccination with the PAP-J gene broke its self-tolerance against PAP. Remarkably, DNA vaccination with PAP-J inhibited tumor growth in the Transgenic Adenocarcinoma of the Mouse Prostate (TRAMP) mouse model that closely resembled human PCa. Therefore, this study highlights a novel cancer immunotherapy approach with the potential to control PCa in clinical settings.

Topics: Acid Phosphatase; Amino Acid Motifs; Amino Acid Sequence; Animals; Antibodies; Antigens, Neoplasm; Cancer Vaccines; Cell Line; Disease Models, Animal; Disease Progression; Epitopes; Genetic Vectors; H-2 Antigens; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Peptides; Prostatic Neoplasms; Protein Binding; Protein Tyrosine Phosphatases; Self Tolerance; T-Lymphocytes, Cytotoxic; Vaccines, DNA

Sipuleucel-T was approved by the US Food and Drug Administration on April 29, 2010, as an immunotherapy for late-stage prostate cancer. To manufacture sipuleucel-T, mononuclear cells harvested from the patient are incubated with a recombinant prostatic acid phosphatase (PAP) antigen and reinfused. The manufacturer proposes that antigen-presenting cells exogenously activated by PAP induce endogenous T-cells to attack PAP-bearing prostate cancer cells. However, the lack of demonstrable tumor responses has prompted calls for scrutiny of the design of the trials in which sipuleucel-T demonstrated a 4-month survival benefit. Previously unpublished data from the sipuleucel-T trials show worse overall survival in older vs younger patients in the placebo groups, which have not been shown previously to be prognostic for survival in castration-resistant prostate cancer patients receiving chemotherapy. Because two-thirds of the cells harvested from placebo patients, but not from the sipuleucel-T arm, were frozen and not reinfused, a detrimental effect of this large repeated cell loss provides a potential alternative explanation for the survival "benefit." Patient safety depends on adequately addressing this alternative explanation for the trial results.

Topics: Acid Phosphatase; Age Factors; Aged; Aged, 80 and over; Aging; Cancer Vaccines; Clinical Trials as Topic; Humans; Immunotherapy; Male; Middle Aged; Neoplasms, Hormone-Dependent; Patient Selection; Prognosis; Prostatic Neoplasms; Protein Tyrosine Phosphatases; Research Design; Survival Analysis; Tissue Extracts

Molecular classification of diseases based on multigene expression signatures is increasingly used for diagnosis, prognosis, and prediction of response to therapy. Immunohistochemistry (IHC) is an optimal method for validating expression signatures obtained using high-throughput genomics techniques since IHC allows a pathologist to examine gene expression at the protein level within the context of histologically interpretable tissue sections. Additionally, validated IHC assays may be readily implemented as clinical tests since IHC is performed on routinely processed clinical tissue samples. However, methods have not been available for automated n-gene expression profiling at the protein level using IHC data. We have developed methods to compute expression level maps (signature maps) of multiple genes from IHC data digitized on a commercial whole slide imaging system. Areas of cancer for these expression level maps are defined by a pathologist on adjacent, co-registered H&E slides, allowing assessment of IHC statistics and heterogeneity within the diseased tissue. This novel way of representing multiple IHC assays as signature maps will allow the development of n-gene expression profiling databases in three dimensions throughout virtual whole organ reconstructions.

Topics: Acid Phosphatase; Antigens, CD34; Biomarkers, Tumor; Databases, Genetic; Gene Expression Profiling; Humans; Immunohistochemistry; Ki-67 Antigen; Male; Phosphopyruvate Hydratase; Prostatic Neoplasms; Protein Array Analysis; Protein Tyrosine Phosphatases; Software

Prostatic acid phosphatase (PAP) is a prostate cancer tumor antigen and is an immunological target in several active immunotherapy clinical trials for the treatment of prostate cancer. We and others have demonstrated that PAP-specific T-cell responses can be elicited and augmented following antigen-specific immunization in both humans and animal models. We have previously reported that prostate cancer patients immunized with a DNA vaccine encoding PAP (pTVG-HP) developed both CD4+ and CD8+ T-cell responses. PAP-specific, CD4+ T-cell proliferative responses were generated in three out of four HLA-DRB1*0101 patients suggesting the possibility that DR1-restricted epitopes exist.. To identify PAP-specific HLA-DRB1*0101 restricted epitopes, we immunized HLA-A2.01/HLA-DRB1*0101 (A2/DR1) transgenic mice with the pTVG-HP DNA vaccine. To map DRB1*0101-restricted epitopes, splenocytes from immunized mice were screened against a library of overlapping 15-residue, PAP-derived peptides using an IFNγ ELISPOT assay.. We identified four HLA-DRB1*0101 epitopes for PAP in A2/DR1 mice (PAP(161-175) , PAP(181-195) , PAP(191-205) , and PAP (351-365) ). T cells specific for one epitope (PAP(181-195) ) were found to be augmented after immunization in a HLA-DRB1*0101+ prostate cancer patient.. The identification of MHC class II epitopes may provide tools to directly monitor immune responses after vaccination and may be important for the design of future prostate cancer vaccines.

Topics: Acid Phosphatase; Amino Acid Sequence; Animals; CD4-Positive T-Lymphocytes; Epitope Mapping; Epitopes, T-Lymphocyte; HLA-A2 Antigen; HLA-DR1 Antigen; Humans; Leukocytes, Mononuclear; Male; Mice; Mice, Transgenic; Molecular Sequence Data; Prostate; Prostatic Neoplasms; Protein Tyrosine Phosphatases; T-Lymphocytes; Vaccines, DNA

Ductal adenocarcinoma of the prostate is considered to be a rare variant of prostatic adenocarcinoma when compared to the more common acinar adenocarcinoma. We report here a case of ductal adenocarcinoma of the prostate in a 68-year old man who presented with complaints of abdominal pain, retention of urine and hematuria of one month duration. Clinical examination showed prostatomegaly. The serum Prostate Specific Antigen (PSA) value was raised to 79ng/mL. Histopathological and immunohistochemical evaluation of resected specimen of prostate revealed ductal adenocarcinoma of the prostate. The patient was lost to follow up and presented four years after the initial diagnosis with metastasis to the bone and testis. Though prostatic cancers have the ability for wide spread dissemination, metastasis to testis is rare. Immunohistochemical staining with PSA and Prostatic Acid Phosphatase (PAP) can help in establishing prostatic nature of the neoplasm. We are reporting this case because of the rarity of metastasis of prostatic carcinoma to testis and for stressing the need for keeping in mind the possibility of metastatic carcinoma also while dealing with testicular tumors.

Topics: Acid Phosphatase; Adenocarcinoma; Aged; Humans; Male; Prostate-Specific Antigen; Prostatic Neoplasms; Protein Tyrosine Phosphatases; Testicular Neoplasms

We report a novel continuous and sensitive fluorescence turn-on assay for ACPs, which consists of a cationic conjugated polyelectrolyte (PPE4+) and a commonly used phosphatase substrate p-nitrophenyl phosphate (pNPP). The kinetics of the ACP catalyzed hydrolysis of the substrate pNPP was monitored by the fluorescence change of PPE4+ and corresponding kinetic parameters were derived to be consistent with the literature reports. The applications of PPE4+/pNPP-based ACP assay in high-throughput screening of ACP inhibitors and detection of prostatic acid phosphotase (PAP) in vitro were demonstrated.

Topics: Acid Phosphatase; Aniline Compounds; Catalysis; Drug Design; Electrolytes; Humans; Hydrolysis; Kinetics; Male; Models, Chemical; Nitrophenols; Organophosphorus Compounds; Phosphoric Monoester Hydrolases; Polymers; Prostatic Neoplasms; Protein Tyrosine Phosphatases; Spectrometry, Fluorescence

For primary bladder tumors, distinguishing urothelial carcinoma (UC) invading the fibromuscular stroma of the prostate (pT4a) from in situ UC involving prostatic ducts can be difficult. Immunohistochemical markers (cytokeratin [CK]5/6, CK5, CK7, CK20, p53, p63, high-molecular-weight keratin [HMWK], androgen receptor, prostate-specific antigen [PSA], prostate specific acid phosphatase [PSAP], laminin, CD44s, CD141) were assessed for their usefulness in determining depth of UC invasion in the prostate. In cystoprostatectomy specimens containing in situ UC in prostatic ducts, both CK5/6 and CK5 clearly differentiated prostatic basal cells from in situ UC. The remaining markers were not effective in determining depth of tumor invasion. Double-stain combinations CK7/CK5 and p53/CK5 were performed and robustly color contrasted in situ tumor from surrounding basal cells. The use of CK5/6, CK5, CK7/CK5, or p53/CK5 is recommended to assist in determining the depth of UC invasion in the prostate when histologic findings are equivocal.

Topics: Acid Phosphatase; Biomarkers, Tumor; Carcinoma in Situ; Humans; Hyaluronan Receptors; Keratin-20; Keratin-5; Keratin-6; Keratin-7; Laminin; Male; Neoplasm Invasiveness; Neoplasm Staging; Prostate-Specific Antigen; Prostatic Neoplasms; Tumor Suppressor Protein p53; Urinary Bladder Neoplasms; Urothelium

The Youden index, a main summary index for the receiver operating characteristic (ROC) curve, is a comprehensive measurement for the effectiveness of a diagnostic test. For a continuous-scale diagnostic test, the optimal cut point for positive disease is the cut point leading to the maximization of the sum of sensitivity and specificity. Finding the Youden index of the test is equivalent to maximize the sum of sensitivity and specificity for all the possible values of the cut point. In this paper, we propose new nonparametric confidence intervals for the Youden index. Extensive simulation studies are conducted to compare the relative performance of the new intervals with the existing parametric interval for the index. Our simulation results indicate that the newly developed nonparametric intervals are competitive with the existing parametric interval when the underlying distributions are correctly specified, and they outperform the existing parametric interval when the underlying distributions are misspecified. The new intervals are robust and easy to implement in practice. A real example is also used to illustrate the application of the proposed intervals.

Topics: Acid Phosphatase; Biomarkers; Computer Simulation; Confidence Intervals; Diagnostic Tests, Routine; Humans; Male; Models, Statistical; Neoplasm Metastasis; Prostatic Neoplasms; ROC Curve; Statistical Distributions; Statistics, Nonparametric

Regulatory T cells play important roles in cancer development and progression by limiting the generation of innate and adaptive anti-tumor immunity. We hypothesized that in addition to natural CD4(+)CD25(+) regulatory T cells (Tregs) and myeloid-derived suppressor cells, tumor Ag-specific Tregs interfere with the detection of anti-tumor immunity after immunotherapy. Using samples from prostate cancer patients immunized with a DNA vaccine encoding prostatic acid phosphatase (PAP) and a trans-vivo delayed-type hypersensitivity (tvDTH) assay, we found that the detection of PAP-specific effector responses after immunization was prevented by the activity of PAP-specific regulatory cells. These regulatory cells were CD8(+)CTLA-4(+), and their suppression was relieved by blockade of CTLA-4, but not IL-10 or TGF-β. Moreover, Ag-specific CD8(+) Tregs were detected prior to immunization in the absence of PAP-specific effector responses. These PAP-specific CD8(+)CTLA-4(+) suppressor T cells expressed IL-35, which was decreased after blockade of CTLA-4, and inhibition of either CTLA-4 or IL-35 reversed PAP-specific suppression of tvDTH response. PAP-specific CD8(+)CTLA-4(+) T cells also suppressed T cell proliferation in an IL-35-dependent, contact-independent fashion. Taken together, these findings suggest a novel population of CD8(+)CTLA-4(+) IL-35-secreting tumor Ag-specific Tregs arise spontaneously in some prostate cancer patients, persist during immunization, and can prevent the detection of Ag-specific effector responses by an IL-35-dependent mechanism.

Topics: Acid Phosphatase; Animals; Cancer Vaccines; CD8-Positive T-Lymphocytes; Cells, Cultured; Clinical Trials as Topic; Coculture Techniques; CTLA-4 Antigen; Epitopes, T-Lymphocyte; Growth Inhibitors; Humans; Interleukins; Male; Mice; Mice, SCID; Prostatic Neoplasms; Protein Tyrosine Phosphatases; T-Lymphocytes, Regulatory; Tumor Escape; Vaccines, DNA

Zinc is an important micronutrient involved in structural and regulatory functions in mammalian cells. It inhibits proliferation of both androgen-dependent and -independent prostate cancer in vitro. However, no report is available on the chemopreventive role of zinc on prostate cancer initiation in in vivo model. The main purpose of this study was to assess the chemopreventive effects of zinc on prostate carcinogenesis induced by a single dose of N-methyl-N-nitrosourea (MNU) and continuous testosterone administration in Sprague-Dawley rats.. In this study, prostate cancer was induced in Sprague-Dawley rats using MNU+ testosterone (MNU + T). Rats were simultaneously treated with zinc (100 ppm) thrice a week. Serum and tissue activity of prostatic acid phosphatase (PAcP) was measured using biochemical analysis. Serum and tissue zinc levels were assessed by atomic absorption spectrophotometry. The ventral prostatic citrate level, phase I drug-metabolizing enzymes such as cytochrome P450, cytochrome b(5), cytochrome b(5) reductase, cytochrome C reductase, phase II enzyme like glutathione-S-transferase, lipid peroxidation, hydrogen peroxide (H(2)O(2)), and reduced glutathione were also analyzed by biochemical assays. Protein expressions of p53, proliferating cell nuclear antigen (PCNA), caspase-3, and B-cell lymphoma protein-X(L) (Bcl-X(L)) were detected by Western blot analysis. Histopathological evaluation of ventral prostate was studied using hematoxylin and eosin staining method.. MNU + T-treated rats showed 60, 50, and 30% of hyperplastic, dysplastic, and prostatic intraepithelial neoplastic changes, respectively, in ventral prostate, whereas MNU + T along with zinc-treated rats showed an incidence of each 10% of hyperplasia, dysplasia, and prostatic intraepithelial neoplasia in the ventral prostate. Serum zinc level and PAcP activity were significantly increased in MNU + T-treated rats, whereas these were decreased in zinc-treated rats. The ventral prostatic PAcP and glutathione-S-transferase activities, zinc, citrate, reduced glutathione levels, and protein levels of p53, caspase-3 were significantly decreased in MNU + T-treated rats, whereas increased in zinc-treated rats. Phase I drug-metabolizing enzyme activities, lipid peroxidation, H(2)O(2) levels, PCNA, and Bcl-X(L) levels were increased in MNU + T-treated rats, whereas these levels were restored to within normal limits in zinc-treated rats.. This study suggests that zinc may have a beneficial effect against MNU and testosterone-induced prostate carcinogenesis. Thus, it may act as a potential chemopreventive agent in targeting the prostate cancer.

Topics: Acid Phosphatase; Animals; Anticarcinogenic Agents; bcl-X Protein; Body Weight; Lipid Peroxidation; Male; Methylnitrosourea; Organ Size; Prostatic Neoplasms; Rats; Rats, Sprague-Dawley; Testosterone; Tumor Suppressor Protein p53; Zinc

Topics: Acid Phosphatase; Adenocarcinoma; Antigen-Presenting Cells; Antigens, Neoplasm; Cancer Vaccines; Clinical Trials, Phase III as Topic; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Male; Prostatic Neoplasms; Recombinant Fusion Proteins; T-Lymphocytes, Cytotoxic; T-Lymphocytes, Regulatory; Tissue Extracts

With the exception of skin cancer, prostatic adenocarcinoma represents the most common cancer among men in the United States and the second most common cause of cancer mortality. Mortality is often associated with metastatic disease, which in the case of prostatic adenocarcinoma typically involves bones and only rarely affects the skin. Although clinical history and examination, laboratory tests and routine pathology can suggest the prostate as a source of metastatic disease, immunohistochemistry - specifically, for prostate-specific antigen (PSA) - is often used to help establish the diagnosis. We report a case of cutaneous metastatic prostatic adenocarcinoma presenting in the inguinal region of a 78-year-old man 5 years after his initial diagnosis. The case is unusual in that the clinical appearance mimicked a vascular proliferation and in that the metastatic prostatic adenocarcinoma failed to express PSA. Rather, expression of prostatic acid phosphatase was observed.

Topics: Acid Phosphatase; Adenocarcinoma; Aged; Humans; Immunohistochemistry; Male; Prostate-Specific Antigen; Prostatic Neoplasms; Protein Tyrosine Phosphatases; Skin Neoplasms; Transurethral Resection of Prostate

Sipuleucel-T (PROVENGE; Dendreon) is the first therapeutic cancer vaccine to be approved by the U.S. Food and Drug Administration. In men who have metastatic castration-resistant prostate cancer with no or minimal symptoms, sipuleucel-T prolongs median survival by 4.1 months compared with results in those treated with placebo. At 3 years, the proportion of patients in the vaccine group who were alive was 50% higher than that in the control group (31.7% versus 21.7%, respectively). Sipuleucel-T, which is designed to elicit an immune response to prostatic acid phosphatase, uses the patient's own immune system to recognize and combat his cancer. Currently, no other agents are available that offer a survival benefit for this population of asymptomatic patients who have not been treated with chemotherapy, except for docetaxel (whose inherent toxicities often lead patients and physicians to delay administration until symptoms develop). Straightforward strategies to increase the efficacy of sipuleucel-T are likely to provide even greater benefit. The preclinical and clinical development of sipuleucel-T is reviewed, and approaches to enhance efficacy are considered herein.

Topics: Acid Phosphatase; Cancer Vaccines; Clinical Trials as Topic; Drug Approval; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Immunization; Leukocytes, Mononuclear; Male; Prostatic Neoplasms; Protein Tyrosine Phosphatases; Recombinant Fusion Proteins; Tissue Extracts; United States; United States Food and Drug Administration

Prostate cancer is the most common cancer and the second leading cause of cancer deaths among males in most Western countries. Autologous cellular immunotherapy for the treatment of cancer seeks to induce tumor-specific immunity in the patient and is consequently dependent on a suitable target antigen and effective presentation of that antigen to the patient's immune system. Prostatic acid phosphatase (PAP) has been tested as a target antigen due to its high and apparently specific expression in the prostate. We used a variety of approaches to analyze PAP expression, including immunohistochemistry, in situ hybridization, and quantitative polymerase chain reaction. We complemented these laboratory-based techniques with an in silico analysis of reported PAP expression in human cDNA libraries. Our studies confirmed that, while PAP expression is not restricted to prostate tissues, its expression in other human tissues is approximately 1-2 orders of magnitude less than that observed in the prostate. The relative specificity of PAP expression in the prostate supports its use as a target of autologous cellular immunotherapy. The approach described here, involving the use of multiple correlates of tissue-specific expression, is warranted as a prerequisite in selecting any suitable target for immunotherapy.

Topics: Acid Phosphatase; Aged; Carcinoma; Humans; Immunohistochemistry; In Situ Hybridization; Male; Middle Aged; Organ Specificity; Pancreas; Prostate; Prostatic Neoplasms; Protein Tyrosine Phosphatases; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger

Vitamin D is considered as an important determinant of bone turnover as well as cancer growth. Using a murine model of bone metastasis, we investigated the effect of vitamin D deficiency on prostate cancer cell growth in bone.. Three-week-old male nude mice were fed either normal chow (control) or a diet deficient in vitamin D. The latter diet resulted in severe hypovitaminosis D within 6 weeks. At this point of time, 5 × 10(4)  cells of the prostate cancer cell line, PC-3, were injected either into the bone marrow (tibia) or subcutaneously into soft tissues. Osteoprotegerin (OPG) was co-administered in subgroups of mice to suppress bone remodeling. Osteolytic lesions were monitored by serial X-ray, while soft tissue tumor growth was measured by caliper. All tissues were analyzed by micro-CT and histology at endpoint.. Bone turnover was significantly accelerated in vitamin D deficient compared to vitamin D sufficient mice from week 6 onwards. Intra-tibially implanted PC-3 cells resulted in mixed osteolytic and osteosclerotic lesion. At endpoint, osteolytic and osteosclerotic lesion areas, total tumor area, and tumor mitotic activity were all significantly increased in vitamin D deficient mice compared to controls. Regardless of diet, OPG reduced bone turnover, total tumor, and osteosclerotic area as well as tumor mitotic activity, while promoting cell apoptosis. In contrast, vitamin D deficiency did not alter tumor growth in soft tissues.. Vitamin D deficiency stimulates prostate cancer growth in bone through modulating the bone microenvironment.

Topics: Acid Phosphatase; Animals; Bone Neoplasms; Bone Remodeling; Calcitriol; Cell Line, Tumor; Histocytochemistry; Isoenzymes; Male; Mice; Mice, Inbred BALB C; Mice, Nude; Osteoprotegerin; Peptide Fragments; Procollagen; Prostatic Neoplasms; Specific Pathogen-Free Organisms; Tartrate-Resistant Acid Phosphatase; Tomography, X-Ray Computed; Vitamin D; Vitamin D Deficiency

MVA-BN-PRO (BN ImmunoTherapeutics) is a candidate immunotherapy product for the treatment of prostate cancer. It encodes 2 tumor-associated antigens, prostate-specific antigen (PSA), and prostatic acid phosphatase (PAP), and is derived from the highly attenuated modified vaccinia Ankara (MVA) virus stock known as MVA-BN. Past work has shown that the immunogenicity of antigens can be improved by targeting their localization to exosomes, which are small, 50- to 100-nm diameter vesicles secreted by most cell types. Exosome targeting is achieved by fusing the antigen to the C1C2 domain of the lactadherin protein. To test whether exosome targeting would improve the immunogenicity of PSA and PAP, 2 additional versions of MVA-BN-PRO were produced, targeting either PSA (MVA-BN-PSA-C1C2) or PAP (MVA-BN-PAP-C1C2) to exosomes, while leaving the second transgene untargeted. Treatment of mice with MVA-BN-PAP-C1C2 led to a striking increase in the immune response against PAP. Anti-PAP antibody titers developed more rapidly and reached levels that were 10- to 100-fold higher than those for mice treated with MVA-BN-PRO. Furthermore, treatment with MVA-BN-PAP-C1C2 increased the frequency of PAP-specific T cells 5-fold compared with mice treated with MVA-BN-PRO. These improvements translated into a greater frequency of tumor rejection in a PAP-expressing solid tumor model. Likewise, treatment with MVA-BN-PSA-C1C2 increased the antigenicity of PSA compared with treatment with MVA-BN-PRO and resulted in a trend of improved antitumor efficacy in a PSA-expressing tumor model. These experiments confirm that targeting antigen localization to exosomes is a viable approach for improving the therapeutic potential of MVA-BN-PRO in humans.

Topics: Acid Phosphatase; Adenocarcinoma; Animals; Antibodies, Neoplasm; Antigens, Neoplasm; Antigens, Surface; Cancer Vaccines; Drug Delivery Systems; Exosomes; Humans; Immunotherapy, Active; Male; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Milk Proteins; Prostate-Specific Antigen; Prostatic Neoplasms; Protein Structure, Tertiary; Protein Tyrosine Phosphatases; Th1 Cells; Vaccines, Attenuated; Vaccinia virus; Xenograft Model Antitumor Assays

A central question in cancer biology is what changes cause a healthy cell to form a tumor. Gene expression data could provide insight into this question, but it is difficult to distinguish between a gene that causes a change in gene expression from a gene that is affected by this change. Furthermore, the proteins that regulate gene expression are often themselves not regulated at the transcriptional level. Here we propose a Bayesian modeling framework we term RegNetB that uses mechanistic information about the gene regulatory network to distinguish between factors that cause a change in expression and genes that are affected by the change. We test this framework using human gene expression data describing localized prostate cancer progression.. The top regulatory relationships identified by RegNetB include the regulation of RLN1, RLN2, by PAX4, the regulation of ACPP (PAP) by JUN, BACH1 and BACH2, and the co-regulation of PGC and GDF15 by MAZ and TAF8. These target genes are known to participate in tumor progression, but the suggested regulatory roles of PAX4, BACH1, BACH2, MAZ and TAF8 in the process is new.. Integrating gene expression data and regulatory topologies can aid in identifying potentially causal mechanisms for observed changes in gene expression.

Topics: Acid Phosphatase; Bayes Theorem; Carcinoma; DNA-Binding Proteins; Gene Expression Regulation, Neoplastic; Gene Regulatory Networks; Homeodomain Proteins; Humans; Male; Paired Box Transcription Factors; Prostate; Prostatic Neoplasms; Protein Tyrosine Phosphatases; Transcription Factor TFIID; Transcription Factors

The Youden index is a widely used measure in the framework of medical diagnostics, where the effectiveness of a biomarker (screening marker or predictor) for classifying a disease status is studied. When the biomarker is continuous, it is important to determine the threshold or cut-off point to be used in practice for the discrimination between diseased and healthy populations. We introduce two methods aimed at estimating the Youden index and its associated threshold. The first one is a modified version of a recent approach based on the delta method, and the second one is based on the adjusted empirical likelihood for quantiles in the setting of a two-sample problem. We also include CIs for both of them. In the simulation study, we compare both methods under different scenarios. Finally, a real example of prostatic cancer, well known in the literature, is analysed to provide the reader with a better understanding of the new methodology.

Topics: Acid Phosphatase; Biomarkers; Humans; Likelihood Functions; Male; Models, Statistical; Prostatic Neoplasms; Statistics, Nonparametric

We identified the molecular target by histone deacetylase (HDAC) inhibitors for exploring their potential prostate cancer (PCa) therapy. Upon HDAC inhibitors-treatment, LNCaP cell growth was suppressed, correlating with increased cellular prostatic acid phosphatase (cPAcP) expression, an authentic protein tyrosine phosphatase. In those cells, ErbB-2 was dephosphorylated, histone H3/H4 acetylation and methylation increased and cyclin proteins decreased. In PAcP shRNA-transfected C-81 cells, valproic acid (VPA) efficacy of growth suppression was diminished. Further, VPA pre-treatment enhanced androgen responsiveness of C-81, C4-2 and MDA PCa2b-AI cells. Thus, cPAcP expression is involved in growth suppression by HDAC inhibitors in PCa cells, and VPA pre-treatments increase androgen responsiveness.

Topics: Acid Phosphatase; Antineoplastic Agents; Blotting, Northern; Blotting, Western; Cell Line, Tumor; Cell Proliferation; Cell Separation; Flow Cytometry; Histone Deacetylase Inhibitors; Humans; Male; Phosphorylation; Prostatic Neoplasms; Protein Tyrosine Phosphatases; Receptor, ErbB-2; Valproic Acid

Previous studies have suggested that zinc exerts anticarcinogenic and antiproliferative effects against prostate cancer both in vitro and in rat ventral prostate. Zinc accumulation diminishes early in the course of prostate malignancy and it inhibits the growth of several carcinoma cells through induction of cell cycle arrest and apoptosis. In this study, we have investigated the influence of zinc on N-methyl-N-nitrosourea (MNU) and testosterone (T)-induced prostatic intraepithelial neoplasia in the dorsolateral prostate of Sprague Dawley (SD) rats. The results indicate that zinc plays an important role in prostate carcinogenesis. Increased tumor incidence was accompanied by a decrease in prostatic acid phosphatase activity, citrate, zinc, glutathione-S-transferase, reduced glutathione, p53, B-cell lymphoma protein (Bcl-2)-associated X protein and caspase-3 levels in MNU + T-treated rats. On the contrary, significantly increased phase I drug metabolizing enzyme activities, lipid peroxide, hydrogen peroxide, proliferating cell nuclear antigen, Bcl-2 and Bcl-X(L) protein levels were observed in the dorsolateral prostate of MNU + T-treated rats. Simultaneous zinc supplementation significantly reversed these effects in MNU + T-treated rats. Signs of dysplasia, a characteristic of prostatic intraepithelial neoplasia, were evident in the dorsolateral prostatic tissue sections by MNU + T administration. However, zinc supplementation has reversed these effects in the dorsolateral prostatic histoarchitecture. These results suggest that zinc may act as an essential trace element against MNU and testosterone-induced prostatic preneoplastic progression in SD rats.

Topics: Acid Phosphatase; Animals; Blotting, Western; Carcinogens; Male; Methylnitrosourea; Proliferating Cell Nuclear Antigen; Prostate; Prostatic Neoplasms; Protein Tyrosine Phosphatases; Rats; Rats, Sprague-Dawley; Testosterone; Tumor Suppressor Protein p53; Zinc Compounds

To investigate diagnostic values of the detection of TMPRSS2-ERG gene fusion in metastatic prostate cancer.. A total of 32 fine needle aspiration (FNA) specimens of metastatic prostate carcinomas were retrieved from the pathology files at MD Anderson Cancer Center. The metastatic sites included the pelvic and remote lymph nodes, liver, bone, and thyroid gland. Immunohistochemical staining for PSA, PAP, synaptophysin, chromogranin A was performed. TMPRSS2-ERG gene fusion was evaluated on sections of cell blocks by fluorescence in situ hybridization (FISH) using ERG gene break-apart probes.. The mean age of the patients was 67 years. Twenty-six patients had a previous history of prostatic adenocarcinoma, while 6 patients presented initially with metastasis. In 11 patients, the metastatic lesions showed characteristic features of small cell carcinoma (SCC) and were positive for synaptophysin (9/9), chromogranin A (7/8), but negative for prostatic specific antigen (7/7). FISH analysis demonstrated a rearrangement of ERG gene in 10 of 32 cases (31.3%), and the rearrangement was associated with deletion of the 5' ERG gene in 6 cases. In addition, the copy number of ERG rearrangement gene locus was increased in 8 cases. Among the 11 cases with SCC features, a rearrangement of ERG gene was present in 5 cases, of which a deletion of the 5' ERG gene and increased copy number were seen in 3 cases.. TMPRSS2-ERG gene fusion can be evaluated in FNA specimens of metastatic prostate cancer. Metastatic prostate cancers have a high prevalence of TMPRSS2-ERG gene fusion along with a frequent copy number increase of ERG gene. TMPRSS2-ERG gene fusion persists in metastatic prostate cancers and even in those with poorly differentiated SCC features. Therefore, an identification of the TMPRSS2-ERG gene fusion may be used to establish the prostatic origin of metastasis.

Topics: Acid Phosphatase; Adenocarcinoma; Aged; Aged, 80 and over; Biopsy, Fine-Needle; Carcinoma, Small Cell; Chromogranin A; Follow-Up Studies; Gene Fusion; Gene Rearrangement; Humans; In Situ Hybridization, Fluorescence; Liver Neoplasms; Lymphatic Metastasis; Male; Middle Aged; Oncogene Proteins, Fusion; Prostate-Specific Antigen; Prostatic Neoplasms; Protein Tyrosine Phosphatases; Synaptophysin

Prostate cancer (PCa) bone metastases are a major cause of morbidity and mortality. There are no effective therapies for PCa bone metastases that prolong survival. Prostatic acid phosphatase (PAP) is a secretory protein expressed by PCa cells. We demonstrate that PAP is strongly expressed in PCa bone metastases in 7/7 patients, while prostate-specific antigen (PSA) is only weakly expressed. The human PCa cell line VCaP secretes PAP and induces an osteoblastic reaction in bone similar to that seen in human PCa bone metastases. Coculture of MC3T3 mouse preosteoblast cells with VCaP cells induces MC3T3 cell growth and differentiation as measured by alkaline phosphatase secretion, and this effect is inhibited by addition of the PAP-inhibitor, l-tartrate. Taken together, these data indicate that PAP is expressed in PCa bone metastases and may play a causal role in the osteoblastic phase of the disease.

Topics: Acid Phosphatase; Animals; Bone Neoplasms; Cell Differentiation; Cell Line, Tumor; Gene Expression Regulation, Enzymologic; Gene Expression Regulation, Neoplastic; Humans; Male; Mice; Osteoblasts; Osteogenesis; Prostate-Specific Antigen; Prostatic Neoplasms; Protein Tyrosine Phosphatases

Sipuleucel-T is a therapeutic cancer vaccine approved for the treatment of castration- or hormone-refractory prostate cancer. Through a novel process, it activates the body's own antigen-presenting cells to induce an immune response to prostatic acid phosphatase, a protein found on prostate cancer cells. A treatment course consists of three total infusions spread 2 weeks apart. Throughout all phases of clinical trials, sipuleucel-T has been shown to be safe and well tolerated. Sipuleucel-T has demonstrated an ability to increase overall survival by approximately 4 months when compared with placebo. However, sipuleucel-T has not shown any improvement in affecting patients' time to disease progression.

Topics: Acid Phosphatase; Animals; Cancer Vaccines; Clinical Trials as Topic; Drug Administration Schedule; Humans; Male; Orchiectomy; Prostatic Neoplasms; Protein Tyrosine Phosphatases; Tissue Extracts; Treatment Outcome

Prostatic acid phosphatase (PAP) has been investigated as the target of several antigen-specific anti-prostate tumor vaccines. The goal of antigen-specific active immunotherapies targeting PAP would ideally be to elicit PAP-specific CD8+ effector T cells. The identification of PAP-specific CD8+ T-cell epitopes should provide a means of monitoring the immunological efficacy of vaccines targeting PAP, and these epitopes might themselves be developed as vaccine antigens. In the current report, we hypothesized that PAP-specific epitopes might be identified by direct identification of pre-existing CD8+ T cells specific for HLA-A2-restricted peptides derived from PAP in the blood of HLA-A2-expressing individuals. 11 nonamer peptides derived from the amino acid sequence of PAP were used as stimulator antigens in functional ELISPOT assays with peripheral blood mononuclear cells from 20 HLA-A2+ patients with prostate cancer or ten healthy blood donors. Peptide-specific T cells were frequently identified in both groups for three of the peptides, p18-26, p112-120, and p135-143. CD8+ T-cell clones specific for three peptides, p18-26, p112-120, and p299-307, confirmed that these are HLA-A2-restricted T-cell epitopes. Moreover, HLA-A2 transgenic mice immunized with a DNA vaccine encoding PAP developed epitope-specific responses for one or more of these three peptide epitopes. We propose that this method to first identify epitopes for which there are pre-existing epitope-specific T cells could be used to prioritize MHC class I-specific epitopes for other antigens. In addition, we propose that the epitopes identified here could be used to monitor immune responses in HLA-A2+ patients receiving vaccines targeting PAP to identify potentially therapeutic immune responses.

Topics: Acid Phosphatase; Animals; Antigens, Neoplasm; Cancer Vaccines; CD8-Positive T-Lymphocytes; Clone Cells; Epitopes, T-Lymphocyte; HLA-A2 Antigen; Humans; Immunization; Interferon-gamma; Lymphocyte Activation; Male; Mice; Mice, Transgenic; Peptide Fragments; Prostatic Neoplasms; Protein Binding; Protein Tyrosine Phosphatases

To assess the diagnostic accuracy of serum bone turnover markers for detection of bone metastasis in patients with prostate cancer (PCa) and to assess the usefulness of these markers as predictors of mortality from PCa.. Serum total alkaline phosphatase, bone-specific alkaline phosphatase, carboxy-terminal pyridinoline cross-linked telopeptide parts of type-I collagen (1CTP), tartrate-resistant acid phosphatase type 5 b, and prostate-specific antigen (PSA) levels were measured in 222 patients (58 with bone metastasis, 57 with T2M0 PCa, 55 with T3M0 PCa, and 52 without PCa). Multivariate stepwise logistic regression analysis was used to identify independent predictors of bone metastasis. Correlation of serum marker levels with bone metastasis was assessed using receiver operating characteristics analysis. Multivariate Cox proportional hazards analysis was used to predict cause-specific survival in PCa patients with bone metastasis.. Serum total alkaline phosphatase, bone-specific alkaline phosphatase, 1CTP, tartrate-resistant acid phosphatase type 5 b, and PSA levels were significantly elevated in patients with bone metastasis, and correlated significantly with the extent of disease on bone scintigraphy. Multivariate stepwise logistic regression analysis demonstrated that serum PSA and 1CTP were significant predictors of bone metastasis. Receiver operating characteristics analyses showed that serum 1CTP level was the most reliable predictor of bone metastasis (area under the curve = 0.85). Multivariate Cox proportional hazards analysis revealed that only serum 1CTP was an independent prognostic factor for PCa-related death.. Serum 1CTP level was a more reliable marker than the others to detect bone metastatic spread and to predict survival probability in PCa patients with bone metastasis.

Topics: Acid Phosphatase; Adenocarcinoma; Aged; Aged, 80 and over; Alkaline Phosphatase; Analysis of Variance; Biomarkers, Tumor; Bone Neoplasms; Cohort Studies; Collagen Type I; Humans; Immunohistochemistry; Isoenzymes; Kaplan-Meier Estimate; Logistic Models; Male; Middle Aged; Multivariate Analysis; Neoplasm Staging; Probability; Prognosis; Proportional Hazards Models; Prostate-Specific Antigen; Prostatic Neoplasms; Survival Analysis; Tartrate-Resistant Acid Phosphatase

Prostate cancer is one of the most prevalent cancers in men. Replication-competent oncolytic herpes simplex virus (oHSV) vectors are a powerful antitumor therapy that can exert at least two effects: direct cytocidal activity that selectively kills cancer cells and induction of antitumor immunity. In addition, oHSV vectors can also function as a platform to deliver transgenes of interest. In these studies, we have examined the expression of a xenogeneic homologue of the prostate cancer antigen, prostatic acid phosphatase (PAP), with the goal of enhancing virotherapy against PAP-expressing tumors. PAP has already been used for cancer vaccination in patients with prostate cancer. Here we show that treatment with oHSV bPDelta6 expressing xenogeneic human PAP (hPAP) significantly reduces tumor growth and increases survival of C57/BL6 mice bearing mouse TRAMP-C2 prostate tumors, whereas expression of syngeneic mouse PAP (mPAP) from the same oHSV vector did not enhance antitumor activity. Treatment of mice bearing metastatic TRAMP-C2 lung tumors with oHSV-expressing hPAP resulted in fewer tumor nodules. To our knowledge, this is the first report of oncolytic viruses being used to express xenoantigens. These data lend support to the concept of combining oncolytic and immunogenic therapies as a way to improve therapy of metastatic prostate cancer.

Topics: Acid Phosphatase; Animals; Cytotoxicity, Immunologic; Gene Transfer Techniques; Immunization; Male; Mice; Mice, Inbred C57BL; Oncolytic Virotherapy; Oncolytic Viruses; Prostatic Neoplasms; Protein Tyrosine Phosphatases; Simplexvirus; Transgenes

Protein-protein interactions and protein complex/aggregate formation play an essential role in almost all biological functions and activities. Through a nanoparticle aggregation immunoassay, we discovered that some proteins are substantially more complexed/aggregated in cancer tissues than normal tissues. This study examined four biomarkers proteins, CA125, CEA (carcinoembryonic antigen), CA19-9 and PAP (prostatic acid phosphatase) in ovarian, colon and prostate tissue lysates. The most exciting results were observed from the PAP assay of prostate tissues: prostate cancer can be clearly distinguished from normal prostate and prostate with benign conditions such as BPH (benign prostate hyperplasia) based on the complex/aggregation level of PAP in prostate tissue lysates. The complex/aggregate level of a protein can be potential biomarkers for cancer detection and diagnosis.

Topics: Acid Phosphatase; Adult; Aged; Aged, 80 and over; Antibodies; Biomarkers, Tumor; CA-125 Antigen; CA-19-9 Antigen; Carcinoembryonic Antigen; Colonic Neoplasms; Diagnosis, Differential; Female; Gold; Humans; Immunoassay; Male; Membrane Proteins; Metal Nanoparticles; Middle Aged; Neoplasms; Ovarian Neoplasms; Prostatic Hyperplasia; Prostatic Neoplasms; Protein Binding; Protein Conformation; Protein Tyrosine Phosphatases; Proteins; Sensitivity and Specificity

Topics: Acid Phosphatase; Antigens, Neoplasm; Cancer Vaccines; Dendritic Cells; Drug Approval; Humans; Male; Prostatic Neoplasms; Protein Tyrosine Phosphatases; United States; United States Food and Drug Administration

Topics: Acid Phosphatase; Alkaline Phosphatase; Animals; Bone Neoplasms; Dogs; Estrogens; History, 20th Century; Humans; Male; Orchiectomy; Prostatic Neoplasms; Testosterone; United States

Cellular prostatic acid phosphatase (cPAcP), an authentic tyrosine phosphatase, is proposed to function as a negative growth regulator of prostate cancer (PCa) cells in part through its dephosphorylation of ErbB-2. Nevertheless, the direct interaction between cPAcP and ErbB-2 has not been shown nor the specific dephosphorylation site of ErbB-2 by cPAcP. In this report, our data show that the phosphorylation level of ErbB-2 primarily at Tyr(1221/2) correlates with the growth rate of both LNCaP and MDA PCa2b human PCa cells. Further, cPAcP reciprocally co-immunoprecipitated with ErbB-2 in a non-permissive growth condition. Expression of wild type cPAcP, but not inactive mutant, by cDNA in cPAcP-null LNCaP C-81 cells results in decreased tyrosine phosphorylation of ErbB-2 including Tyr(1221/2). Concurrently, Tyr(317) phosphorylation of p52(Shc), proliferating cell nuclear antigen expression, and cell growth are decreased in these cells. Conversely, decreased cPAcP expression by short hairpin RNA in LNCaP C-33 cells was associated with elevated phosphorylation of ErbB-2 initially at Tyr(1221/2). Its downstream p52(Shc), ERK1/2, Akt, Src, STAT-3, and STAT-5 were activated, and cell proliferation, proliferating cell nuclear antigen, and cyclin D1 expression were increased. Stable subclones of C-33 cells by small interfering PAcP had elevated Tyr(1221/2) phosphorylation of ErbB-2 and exhibited androgen-independent growth and increased tumorigenicity in xenograft female animals. In summary, our data together indicate that in prostate epithelia, cPAcP interacts with and dephosphorylates ErbB-2 primarily at Tyr(1221/2) and hence blocks downstream signaling, leading to reduced cell growth. In PCa cells, decreased cPAcP expression is associated with androgen-independent cell proliferation and tumorigenicity as seen in advanced hormone-refractory prostate carcinomas.

Topics: Acid Phosphatase; Animals; Cell Line, Tumor; Cell Proliferation; Female; Gene Expression Regulation, Neoplastic; Humans; Male; Mice; Neoplasm Transplantation; Phosphorylation; Prostatic Neoplasms; Protein Tyrosine Phosphatases; Receptor, ErbB-2; Subcellular Fractions; Tyrosine

Seminal vesicle invasion by prostatic carcinoma is directly associated with tumor staging; verification is challenging when the tumor demonstrates cribriform or papillary growth patterns or there are back-to-back small-gland proliferations. P504S is overexpressed in prostatic carcinoma and high-grade prostatic intraepithelial neoplasia with cytoplasmic immunoreactivity. p63 has positive immunoreactivity in basal cell nuclei of benign prostatic glands. Many researchers use a combination of these antibodies and their different colors.. To evaluate the usefulness of a single-color P504S/p63 cocktail immunostain in verifying prostatic carcinoma within the seminal vesicle.. Sections from 57 radical prostatectomy specimens of pathologic stage pT3b that contain seminal vesicle with prostatic carcinoma involvement were immunostained with primary antibodies against prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP) and a cocktail of antibodies against P504S and p63.. Prostatic carcinoma cells from all 57 cases were diffusely positive for P504S, PSA, and PAP with cytoplasmic staining and no p63 nuclear staining. Seminal vesicle epithelium from all 57 cases was negative for all 3 markers with distinct p63 nuclear staining of the basal cells. Benign prostatic tissue was positive for PSA and PAP, as well as for p63, but negative for P504S.. The P504S/p63 one-color cocktail is a practical and cost-effective stain to differentiate prostatic carcinoma that involves the seminal vesicle from seminal vesicle epithelium. It is superior to PSA or PAP when sections contain both seminal vesicle and benign glands because PSA and PAP cannot distinguish benign from malignant glands.

Topics: Acid Phosphatase; Carcinoma; Cost-Benefit Analysis; Humans; Immunohistochemistry; Male; Membrane Proteins; Neoplasm Invasiveness; Neoplasm Staging; Prostate; Prostate-Specific Antigen; Prostatectomy; Prostatic Neoplasms; Protein Tyrosine Phosphatases; Racemases and Epimerases; Seminal Vesicles; Staining and Labeling

NKX3.1 is a prostatic tumor suppressor gene located on chromosome 8p. Although most studies have shown that staining for NKX3.1 protein is positive in the majority of primary prostatic adenocarcinomas, it has been shown to be downregulated in many high-grade prostate cancers, and completely lost in the majority of metastatic prostate cancers (eg, in 65% to 78% of lesions). A recent study showed that NKX3.1 staining with a novel antibody was highly sensitive and specific for high-grade prostatic adenocarcinoma when compared with high-grade urothelial carcinoma. This raised the question that this antibody may perform better than earlier used antibodies in metastatic prostate tumors. However, the sensitivity and specificity for prostate carcinomas for this antibody in metastatic lesions was not determined. Although prostate-specific antigen (PSA) and prostatic-specific acid phosphatase (PSAP) are excellent tissue markers of prostate cancer, at times they may be expressed at low levels, focally, or not at all in poorly differentiated primary and metastatic prostatic adenocarcinomas. The purpose of this study was to determine the performance of NKX3.1 as a marker of metastatic adenocarcinoma of prostatic origin. Immunohistochemical staining against NKX3.1, PSA, and PSAP was carried out on a tissue microarray (TMA) (0.6-mm tissue cores) of hormone naïve metastatic prostate adenocarcinoma specimens from lymph nodes, bone, and soft tissue. To determine the specificity of NKX3.1 for prostatic adenocarcinoma, we used TMAs that contained cancers from various sites including the urinary bladder, breast, colon, salivary gland, stomach, pancreas, thyroid, and central nervous system, and standard paraffin sections of cancers from other sites including the adrenal cortex, kidney, liver, lung, and testis. Overall 349 nonprostatic tumors were evaluated. Any nuclear staining for NKX3.1 was considered positive and the percentage of cells with nuclear staining and their mean intensity level were assessed visually. Sensitivity was calculated by considering a case positive if any TMA core was positive. The sensitivity for identifying metastatic prostatic adenocarcinomas overall was 98.6% (68/69 cases positive) for NKX3.1, 94.2% (65/69 cores positive) for PSA, and 98.6% (68/69 cores positive) for PSAP. The specificity of NKX3.1 was 99.7% (1/349 nonprostatic tumors positive). The sole positive nonprostatic cancer case was an invasive lobular carcinoma of the breast. NKX3.1 seems

Topics: Acid Phosphatase; Adenocarcinoma; Antibody Specificity; Biomarkers, Tumor; Bone Neoplasms; Cell Differentiation; Homeodomain Proteins; Humans; Immunohistochemistry; Lymph Nodes; Male; Neoplasms, Unknown Primary; Predictive Value of Tests; Prostate-Specific Antigen; Prostatic Neoplasms; Protein Tyrosine Phosphatases; Sensitivity and Specificity; Soft Tissue Neoplasms; Tissue Array Analysis; Transcription Factors

Prostate carcinoma is among the most common solid tumors to secondarily involve the male breast. Prostate specific antigen (PSA) and prostate-specific acid phosphatase (PSAP) are expressed in benign and malignant prostatic tissue, and immunohistochemical staining for these markers is often used to confirm the prostatic origin of metastatic carcinoma. PSA expression has been reported in male and female breast carcinoma and in gynecomastia, raising concerns about the utility of PSA for differentiating prostate carcinoma metastasis to the male breast from primary breast carcinoma. This study examined the frequency of PSA, PSAP, and hormone receptor expression in male breast carcinoma (MBC), female breast carcinoma (FBC), and gynecomastia.. Immunohistochemical staining for PSA, PSAP, AR, ER, and PR was performed on tissue microarrays representing six cases of gynecomastia, thirty MBC, and fifty-six FBC.. PSA was positive in two of fifty-six FBC (3.7%), focally positive in one of thirty MBC (3.3%), and negative in the five examined cases of gynecomastia. PSAP expression was absent in MBC, FBC, and gynecomastia. Hormone receptor expression was similar in males and females (AR 74.1% in MBC vs. 67.9% in FBC, p = 0.62; ER 85.2% vs. 68.5%, p = 0.18; and PR 51.9% vs. 48.2%, p = 0.82).. PSA and PSAP are useful markers to distinguish primary breast carcinoma from prostate carcinoma metastatic to the male breast. Although PSA expression appeared to correlate with hormone receptor expression, the incidence of PSA expression in our population was too low to draw significant conclusions about an association between PSA expression and hormone receptor status in breast lesions.

Topics: Acid Phosphatase; Aged; Breast Neoplasms; Breast Neoplasms, Male; Carcinoma; Diagnosis, Differential; Female; Gynecomastia; Humans; Immunohistochemistry; Male; Middle Aged; Predictive Value of Tests; Prostate-Specific Antigen; Prostatic Neoplasms; Protein Tyrosine Phosphatases; Receptors, Androgen; Receptors, Estrogen; Receptors, Progesterone; Receptors, Steroid; Tissue Array Analysis

Topics: Acid Phosphatase; Biomarkers, Tumor; Humans; Male; Prostatic Neoplasms; Protein Tyrosine Phosphatases

Metastasis to bone is the leading cause of morbidity and mortality in advanced prostate cancer patients. Considering the complex reciprocal interactions between the tumor cells and the bone microenvironment, there is increasing interest in developing combination therapies targeting both the tumor growth and the bone microenvironment. In this study, we investigated the effect of simultaneous blockade of BMP pathway and RANK/RANKL axis in an osteolytic prostate cancer lesion in bone. We used a retroviral vector encoding noggin (RetroNoggin) to antagonize the effect of BMPs and RANK:Fc, which is a recombinant RANKL antagonist was used to inhibit RANK/RANKL axis. The tumor growth and bone loss were evaluated using plain radiographs, hind limb tumor measurements, micro PET/CT ((18)FDG and (18)F-fluoride tracer), and histology. Tibias implanted with PC-3 cells developed pure osteolytic lesions at 2-weeks with progressive increase in cortical bone destruction at successive time points. Tibias implanted with PC-3 cells over expressing noggin (RetroNoggin) resulted in reduced tumor size and decreased bone loss compared to the implanted tibias in untreated control animals. RANK:Fc administration inhibited the formation of osteoclasts, delayed the development of osteolytic lesions, decreased bone loss and reduced tumor size in tibias implanted with PC-3 cells. The combination therapy with RANK:Fc and noggin over expression effectively delayed the radiographic development of osteolytic lesions, and decreased the bone loss and tumor burden compared to implanted tibias treated with noggin over expression alone. Furthermore, the animals treated with the combination strategy exhibited decreased bone loss (micro CT) and lower tumor burden (FDG micro PET) compared to animals treated with RANK:Fc alone. Combined blockade of RANK/RANKL axis and BMP pathway resulted in reduced tumor burden and decreased bone loss compared to inhibition of either individual pathway alone in osteolytic prostate cancer lesion in bone. These results suggest that simultaneous targeting of tumor cells and osteoclasts may be the most effective method of inhibiting the progression of established osteolytic metastatic lesions in vivo.

Topics: Acid Phosphatase; Animals; Bone Morphogenetic Proteins; Cell Line, Tumor; Fluorine Radioisotopes; Fluorodeoxyglucose F18; Hindlimb; Humans; Isoenzymes; Male; Mice; Mice, SCID; Neoplasm Transplantation; Osteolysis; Positron-Emission Tomography; Prostatic Neoplasms; RANK Ligand; Receptor Activator of Nuclear Factor-kappa B; Tartrate-Resistant Acid Phosphatase; Tibia; Tomography, X-Ray Computed

Prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP) are glycoproteins secreted by prostate epithelial cells, and have a long clinical history of use as serum biomarkers of prostate cancers. These two proteins are present at significantly higher concentrations in seminal plasma, making this proximal fluid of the prostate a good source for purifying enough protein for characterization of prostate disease associated changes in glycan structures. With the use of seminal fluid samples representative of normal control, benign prostatic disease and prostate cancers, PAP and PSA were enriched by thiophilic absorption chromatography. Released N-linked glycan constituents from both proteins were analyzed by a combination of normal phase HPLC and MALDI-TOF spectrometry. For PSA, 40 putative glycoforms were determined, and 21 glycoforms were determined for PAP. PAP glycans were further analyzed with a hybrid triple quadrupole/linear ion trap mass spectrometer to assign specific glycoform classes to each of the three N-linked sites. The glycans identified in these studies will allow for more defined targeting of prostate disease-specific changes for PAP, PSA and other secreted prostatic glycoproteins.

Topics: Acid Phosphatase; Biomarkers, Tumor; Carbohydrate Conformation; Carbohydrate Sequence; Glycomics; Humans; Male; Molecular Sequence Data; Polysaccharides; Prostate-Specific Antigen; Prostatic Neoplasms; Protein Tyrosine Phosphatases; Semen; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

Epidemiological data indicate that intake of one form of vitamin E, gamma-tocopherol, may reduce prostate cancer risk, and several in vitro studies have demonstrated that gamma-tocopherol can inhibit prostate cancer cell growth. The purpose of the present study was to confirm effects of gamma-tocopherol on prostate cancer in the transgenic rat for adenocarcinoma of prostate (TRAP) model established in our laboratory.. In Experiment 1, heterozygous male TRAP rats 5 weeks of age received alpha-tocopherol at the concentration of 50 mg/kg in the diet, or gamma-tocopherol at 50 or 100 mg/kg for 10 weeks. In Experiment 2, TRAP rats of 3 weeks of age were given gamma-tocopherol at 50, 100, or 200 mg/kg diet for 7 weeks.. gamma-Tocopherol did not affect body weight gain, organ weights or serum levels of either testosterone or estradiol. However, quantitative evaluation of prostatic lesions demonstrated significantly suppression of sequential progression from PIN to adenocarcinoma in a dose-dependent manner, along with clear activation of caspases 3 and 7 in the ventral lobe in both experiments.. The present study clearly demonstrated that gamma-tocopherol suppresses prostate tumor progression in an in vivo TRAP model, and could be a candidate chemopreventive agent for human prostate cancer.

Topics: Acid Phosphatase; Adenocarcinoma; Animals; Animals, Genetically Modified; Antioxidants; Ceramides; Chromatography, High Pressure Liquid; gamma-Tocopherol; Humans; Isoenzymes; Male; Mice; Prostatic Neoplasms; Rats; Tartrate-Resistant Acid Phosphatase; Tocopherols

Clinical management of incidental prostate cancer (IPC) remains challenging since its clinical course cannot be predicted by conventional histopathology. Aiming to define predictive factors in IPC, we correlated the immunohistochemically detected expression of prostate-specific antigen (PSA), prostatic acid phosphatase (PSAP), alpha-methylacyl-CoA racemase (AMACR, p504s), and androgen receptor in transurethral resection specimens with Gleason scores and histologic staging on the corresponding radicals in a cohort of 54 patients (mean age, 65.9 years; range, 49-80 years). PSAP expression showed a significant correlation with tumor staging (rho = -0.37; p = 0.02) but not with Gleason scores (rho = -0.06; p = 0.69). K-statistics revealed a highly significant moderate interobserver agreement concerning the evaluation of PSAP staining (K = 0.47; p < 0.001). In contrast, the other markers assessed failed to correlate with conventional histopathology. Therefore, PSAP might be predictive of tumor stage in IPC and represent a valuable adjunct for clinical decisions in terms of individual therapeutic management.

Topics: Acid Phosphatase; Adenocarcinoma; Aged; Aged, 80 and over; Biomarkers, Tumor; Fluorescent Antibody Technique, Direct; Humans; Immunoenzyme Techniques; Incidental Findings; Male; Middle Aged; Neoplasm Staging; Predictive Value of Tests; Prognosis; Prostate; Prostate-Specific Antigen; Prostatectomy; Prostatic Neoplasms; Protein Tyrosine Phosphatases; Racemases and Epimerases; Transurethral Resection of Prostate

The xenotropic murine leukemia virus-related virus (XMRV) has recently been detected in prostate cancer tissues and may play a role in tumorigenesis. It is currently unclear how this virus is transmitted and which factors promote its spread in the prostate. We show that amyloidogenic fragments known as semen-derived enhancer of virus infection (SEVI) originating from prostatic acid phosphatase greatly increase XMRV infections of primary prostatic epithelial and stromal cells. Hybrid simian/human immunodeficiency chimeric virus particles pseudotyped with XMRV envelope protein were used to demonstrate that the enhancing effect of SEVI, or of human semen itself, was at the level of viral attachment and entry. SEVI enhanced XMRV infectivity but did not bypass the requirement for the xenotropic and polytropic retrovirus receptor 1. Furthermore, XMRV RNA was detected in prostatic secretions of some men with prostate cancer. The fact that the precursor of SEVI is produced in abundance by the prostate indicates that XMRV replication occurs in an environment that provides a natural enhancer of viral infection, and this may play a role in the spread of this virus in the human population.

Topics: Acid Phosphatase; Cell Line, Tumor; Cells, Cultured; Fibroblasts; Gammaretrovirus; Humans; Male; Prostatic Neoplasms; Protein Tyrosine Phosphatases; Retroviridae Infections

Bone metastasis is a frequent and catastrophic consequence of prostate cancer for which only palliative treatment is available. Animal models of bone metastatic prostate cancer are necessary for understanding disease mechanisms but few models exist.. We have used the murine prostate carcinoma cell line RM1 to generate a bone metastatic model of prostate cancer. Repeated intracardiac injection of RM1 cells followed by isolation of cells from bone tumors has yielded a cell line with strong bone-metastatic potential, RM1 bone metastatic (BM).. This cell line metastasizes to multiple bony sites in over 95% of injected C57BL/6 mice and is far less tropic to soft tissues. Bone tumors produced by the RM1(BM) cell line show no preference for particular skeletal sites as most bones are affected. Histology, and micro-computed tomography show that RM1(BM) cells form osteolytic tumors, but with evidence of osteoblastic changes. In vitro the RM1 cells express E-cadherin but not vimentin, do not form colonies in soft agar, are non-invasive but are more motile than the parent cell line.. This model provides a novel means for identifying cellular and molecular mechanisms that contribute to bone metastasis and allow for preclinical testing of therapies to prevent and treat tumor metastasis to bone. Finally as the syngeneic tumor cells are injected into immunocompetent mice, this model will provide a means to study interactions between the immune system, tumors and bone, and therapies that target such interactions.

Topics: Acid Phosphatase; Animals; Bone Neoplasms; Cell Adhesion; Cell Line, Tumor; Cell Movement; Disease Models, Animal; Histocytochemistry; Immunocompetence; Male; Mice; Mice, Inbred C57BL; Microscopy, Fluorescence; Osteocalcin; Prostatic Neoplasms; Tomography, X-Ray Computed

Topics: Acid Phosphatase; Adenocarcinoma; Adjuvants, Immunologic; Cancer Vaccines; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Immunotherapy; Injections, Intradermal; Male; Neoplasm Staging; Prostatic Neoplasms; Protein Tyrosine Phosphatases; Recombinant Proteins; Time Factors; Tissue Extracts; Treatment Outcome; Vaccines, DNA

Survival and capability of cancer cells to form metastases fundamentally depend on interactions with their microenvironment. Secondary tumors originating from prostate carcinomas affect remodeling of bone tissue and can induce both osteolytic and osteocondensing lesions. However, particular molecular mechanisms responsible for selective homing and activity of cancer cells in bone microenvironment have not been clarified yet. Growth/differentiation factor-15 (GDF-15), a distant member of the TGF-beta protein family, has recently been associated with many human cancers, including prostate. We show that both pure GDF-15 and the GDF-15-containing growth medium of 1,25(OH)(2)-vitamin D(3)-treated prostate adenocarcinoma LNCaP cells suppress formation of mature osteoclasts differentiated from RAW264.7 macrophages and bone-marrow precursors by M-CSF/RANKL in a dose-dependent manner. GDF-15 inhibits expression of c-Fos and activity of NFkappaB by delayed degradation of IkappaB. Moreover, GDF-15 inhibits expression of carbonic anhydrase II and cathepsin K, key osteoclast enzymes, and induces changes in SMAD and p38 signaling. The lack of functional osteoclasts can contribute to accumulation of bone matrix by reduction of bone resorption. These results unveil new role of GDF-15 in modulation of osteoclast differentiation and possibly in therapy of bone metastases.

Topics: Acid Phosphatase; Animals; Calcitriol; Carbonic Anhydrase II; Cathepsin K; Cell Differentiation; Cell Line; Cell Line, Tumor; Culture Media, Conditioned; Dose-Response Relationship, Drug; Femur; Growth Differentiation Factor 15; Humans; Isoenzymes; Macrophage Colony-Stimulating Factor; Macrophages; Male; Mice; Mice, Inbred Strains; NF-kappa B; Osteoclasts; Prostatic Neoplasms; Proto-Oncogene Proteins c-fos; RANK Ligand; Tartrate-Resistant Acid Phosphatase; Time Factors

Adenocarcinomas of the bladder are rare, with the diagnosis dependent on exclusion of secondary involvement by direct extension or metastatic spread from other sites. The recent description of an unusual form of urothelial-type mucinous prostatic adenocarcinoma raises a novel differential diagnosis between adenocarcinomas of the prostate and bladder, and investigation into the utility of classic prostatic immunohistochemical antigens in bladder adenocarcinoma is warranted. We identified 37 primary infiltrating adenocarcinomas of the bladder, which included signet ring cell carcinomas (n=11), urachal adenocarcinomas (n=5), and enteric adenocarcinoma (n=21). Also included for comparison were 3 cases, each of bladder villous adenomas and bladder adenocarcinoma in situ. Tissue microarrays were constructed from each case, with each specimen represented by multiple 1.0-mm cores to assess for tumor protein heterogeneity. Immunohistochemistry for prostate-specific antigen (PSA), prostate specific acid phosphatase (PSAP), P501S (prostein), and prostate specific membrane antigen (PSMA) was performed, and moderate to strong immunoreactivity was considered a positive result. Of the 37 adenocarcinomas, all were negative for PSA and PSAP (0/37; 0%). In contrast, a minority of bladder adenocarcinomas was labeled with the prostate antigens P501S and PSMA. P501S showed moderate diffuse cytoplasmic staining in 4/37 cases (11%), including 3 enteric-type adenocarcinomas and 1 mucinous adenocarcinoma. Additionally, 1 case of adenocarcinoma in situ demonstrated diffuse cytoplasmic staining for P501S. The granular perinuclear staining pattern of P501S typically seen in prostatic adenocarcinoma was absent in all cases of bladder adenocarcinoma. PSMA showed diffuse cytoplasmic staining in 4/37 (11%) infiltrating adenocarcinomas (including 1 signet ring carcinoma and 3 enteric-type adenocarcinomas), and in 1 case of adenocarcinoma in situ. Membranous PSMA staining was evident in an additional 3 tumors, 1 urachal mucinous adenocarcinoma, 1 nonurachal mucinous and signet ring cell adenocarcinoma, and 1 nonurachal villous adenoma. In conclusion, although all cases of bladder adenocarcinoma examined were negative for PSA and PSAP, the surprising finding that a subset of invasive and in situ adenocarcinomas of the bladder demonstrated immunoreactivity for P501S and PSMA should warrant caution when using these markers in differentiating prostatic from bladder adenocarcinomas. The lack o

Topics: Acid Phosphatase; Adenocarcinoma; Adenoma, Villous; Antigens, Neoplasm; Diagnosis, Differential; Humans; Immunohistochemistry; Male; Membrane Proteins; Prostate-Specific Antigen; Prostatic Neoplasms; Protein Tyrosine Phosphatases; Tissue Array Analysis; Urinary Bladder Neoplasms

Mature cystic teratomas of the ovary containing prostatic remnants are reported in 2 women aged 31 and 20 years. Both cases showed the expected histology of mature teratomas with a mixture of ecto- and endodermal structures lying in a fibrous stroma. In both cases, the foci of prostate tissue were composed of typical prostatic glands arranged in acinar structures. One case displayed a transitional cell-lined duct resembling the urethra. Prostate glands showed intense positive immunostaining with prostatic specific antigen and prostatic acidic phosphatase. Focal images suggesting high-grade prostatic intraepithelial neoplasia were detected in 1 case. The literature on this unusual finding in these common tumors is reviewed and commented on.

Topics: Acid Phosphatase; Adult; Biomarkers, Tumor; Female; Humans; Male; Ovarian Neoplasms; Ovariectomy; Prostate; Prostate-Specific Antigen; Prostatic Intraepithelial Neoplasia; Prostatic Neoplasms; Protein Tyrosine Phosphatases; Teratoma; Treatment Outcome

During the normal turnover of prostate epithelium, stem cells in the basal cell layer produce an intermediate cell population that gives rise to fully differentiated secretory luminal cells. This process is extensively studied in relation to the development of prostate disease, in particular, to elucidate the origin and nature of prostate cancer. We previously showed that the mRNA of a poorly characterised intercellular adhesion molecule, cadherin-10, is strongly expressed in human prostate. Using anticadherin-10 antibodies, immunohistochemistry, and confocal microscopy, we have examined the pattern of cadherin-10 expression in relation to human prostate epithelial differentiation markers (E-cadherin, CD44, and cytokeratins (CK) 14, 18 and 19) in archival paraffin-embedded and fixed-frozen histopathological specimens in individual and serial sections. In non-neoplastic prostate, E-cadherin is expressed by all basal and luminal epithelial cells, while cadherin-10 is variably expressed in luminal cells where it is colocalised with E-cadherin at basolateral plasma membranes. Cadherin-10 is absent in CK14- and/or CD44-positive basal cells, but is expressed in CK18-positive luminal cells (differentiated secretory cells), a subset of CK19-positive intermediate/luminal cells, but not CK19-positive basal cells. Small foci of prostate cancer express E-cadherin, CK19 and CK18, but cadherin-10 expression is low or undetectable. These findings suggest that the expression of cadherin-10 is associated with the later stages of differentiation of luminal secretory cells, indicating a specific role in secretory cell terminal differentiation. While prostate cancer cells express secretory cell markers (eg, CK18, prostate-specific antigen) and the more generally expressed E-cadherin, their failure to express cadherin-10 further emphasises a role for this cadherin in normal prostate organisation and function.

Topics: Acid Phosphatase; Adenocarcinoma; Biomarkers; Cadherins; Cell Differentiation; Epithelial Cells; Humans; Hyaluronan Receptors; Immunoenzyme Techniques; Keratins; Male; Microscopy, Confocal; Prostate; Prostatic Hyperplasia; Prostatic Neoplasms; Protein Tyrosine Phosphatases

Because prostate cancer is, in its early stages, an androgen-dependent pathology, treatments aiming at decreasing testosterone plasma concentration have been developed for many years now. However, a significant proportion of patients suffer a relapse after a few years of hormone therapy. The androgen-independent stage of prostate cancer has been shown to be associated with the development of neuroendocrine differentiation. We previously demonstrated that neuroendocrine prostate cancer cells derived from LNCaP cells overexpress CaV3.2 T-type voltage-dependent calcium channels. We demonstrate here using prostatic acid phosphatase as a marker of prostate secretion and FM1-43 fluorescence imaging of membrane trafficking that neuroendocrine differentiation is associated with an increase in calcium-dependent secretion which critically relies on CaV3.2 T-type calcium channel activity. In addition, we show that these channels are expressed by neuroendocrine cells in prostate cancer tissues obtained from patients after surgery. We propose that CaV3.2 T-type calcium channel up-regulation may account for the alteration of secretion during prostate cancer development and that these channels, by promoting the secretion of potential mitogenic factors, could participate in the progression of the disease toward an androgen-independent stage.

Topics: Acid Phosphatase; Androgens; Biomarkers, Tumor; Calcium; Calcium Channels, T-Type; Carcinoma, Neuroendocrine; Cell Differentiation; Cell Line, Tumor; Growth Substances; Hormone Replacement Therapy; Humans; Male; Prostatic Neoplasms; Protein Tyrosine Phosphatases; Testosterone; Up-Regulation

To perform a retrospective analysis to assess the utility of pretreatment serum prostatic acid phosphatase (PAP) as a predictor of cause-specific survival (CSS) in patients with higher risk prostate cancer treated with palladium-103 (103Pd) brachytherapy and supplemental external beam radiotherapy (EBRT).. From 1992 to 1996, 193 patients with clinically localized prostate adenocarcinoma, a pretreatment PAP level, and Gleason score 7 or more, and/or a prostate-specific antigen (PSA) level of 10 ng/mL or more were treated with 103Pd brachytherapy and supplemental EBRT. The patients underwent EBRT of 41.4 Gy to a limited pelvic field and 103Pd brachytherapy with a prescribed minimum 103Pd dose of 80 Gy. Multivariate analysis was performed to analyze the predictive value of PAP, PSA, and Gleason score on CSS.. The 10-year CSS rate for patients with a PAP level of less than 1.5, 1.5 to 2.4, and 2.5 U/L or more was 93%, 87%, and 75%, respectively (P = 0.013). The 10-year CSS rate for patients with a PSA level of less than 10, 10 to 20, and greater than 20 ng/mL was 92%, 76%, and 83%, respectively (P = 0.393). The 10-year CSS rate for patients with a Gleason score of 6, 7, 8, and 9 was 90%, 89%, 70%, and 68%, respectively (P = 0.002). On Cox multivariate regression analysis, PAP (hazard ratio 1.31, P <0.0001) and Gleason score (hazard ratio 2.37, P = 0.0007) were associated with CSS. PSA was not predictive of CSS (P = 0.393).. The results of this study demonstrated that PAP is a stronger predictor of CSS than PSA or Gleason score in men with higher risk prostate cancer treated with 103Pd brachytherapy and EBRT. Given the findings of this analysis, the use of PAP should be reconsidered in these patients.

Topics: Acid Phosphatase; Adenocarcinoma; Adult; Aged; Aged, 80 and over; Brachytherapy; Humans; Male; Middle Aged; Multivariate Analysis; Palladium; Predictive Value of Tests; Proportional Hazards Models; Prostatic Neoplasms; Protein Tyrosine Phosphatases; Radioisotopes; Radiotherapy Dosage; Retrospective Studies

Prostate-specific antigen (PSA) and prostate-specific acid phosphatase (PSAP) are produced by prostate carcinoma cells. Their secretion has implications in both prostate cancer diagnosis and progression. The mechanisms involved in PSA and PSAP secretion in response to androgens have remained relatively unknown. The small GTPase Rab27a regulates exocytosis in several tissues. Here, we present methods for the characterization of Rab27a and its effector JFC1/Slp1 as key components of the secretory machinery that regulates exocytosis in prostate carcinoma cells.

Topics: Acid Phosphatase; Cell Line, Tumor; Down-Regulation; Exocytosis; Humans; Male; Membrane Proteins; Permeability; Prostate-Specific Antigen; Prostatic Neoplasms; Protein Interaction Mapping; Protein Structure, Tertiary; Protein Transport; Protein Tyrosine Phosphatases; rab GTP-Binding Proteins; rab27 GTP-Binding Proteins; RNA, Small Interfering; Vesicular Transport Proteins

The clinical value of serum tartrate-resistant acid phosphatase (TRACP), prostate specific antigen (PSA), alkaline phosphatase (ALP), and prostatic acid phosphatase (PACP) for the prediction of bone metastases in prostate cancer were investigated.. TRACP, PACP, ALP, and PSA serum levels were measured in 215 patients with prostate cancer, including 160 without and 55 with bone metastases. Correlation of serum marker levels with bone metastases was assessed using receiver operating characteristics (ROC) analysis. Sensitivity, specificity, accuracy, positive and negative predictive values were calculated for each serum marker. Multivariate stepwise logistic regression analysis was used to identify independent predictors for the presence of bone metastasis.. Mean serum TRACP, PACP, ALP, and PSA levels were significantly elevated in patients with bone metastases compared with those without (P < 0.05). PSA and PACP levels increased significantly with clinical stage of the disease, whereas TRACP and ALP levels only increased significantly in stage D2. Serum TRACP levels correlated significantly with extent of disease on bone scans. ROC analyses showed no significant differences in area under the curve for these markers. Logistic regression analysis demonstrated that PSA, ALP, and TRACP were significant predictors of bone metastasis. Predicted and observed risks of bone metastasis were well correlated when TRACP, ALP, and PSA were combined and bone scan could have been omitted in 70% of patients by assessing these three markers.. Serum TRACP can be considered a useful predictor of bone metastases in prostate cancer. A combination of TRACP, ALP, and PSA can obviate the need for a bone scan in 70% of cases.

Topics: Acid Phosphatase; Aged; Alkaline Phosphatase; Biomarkers; Bone Neoplasms; Humans; Isoenzymes; Male; Predictive Value of Tests; Prostate-Specific Antigen; Prostatic Neoplasms; Tartrate-Resistant Acid Phosphatase

Conventional treatment of recurrent and metastasized prostate cancer (CaP) remains inadequate; this fact mandates development of alternative therapeutic modalities, such as specific active or passive immunotherapy. Previously, we reported the identification of a novel highly immunogenic HLA-A*0201-restricted Prostatic Acid Phosphatase-derived peptide (PAP-3) by a two-step in vivo screening in an HLA-transgenic (HHD) mouse system. In the present study we aimed at elucidating the efficiency of PAP-3-based vaccine upon active antitumor immunization. To this end we established preventive and therapeutic carcinoma models in HHD mice. The 3LL murine Lewis lung carcinoma clone D122 transduced to express HLA-A*0201 and PAP served as a platform for these models. The HLA-A*0201-PAP-3 complex specific recombinant single chain scFV-PAP-3 antibodies were generated and used to confirm an endogenous PAP processing resulting in PAP-3 presentation by HLA-A*0201. PAP-3 based vaccines significantly decreased tumor incidence in a preventive immunization setting. Therapeutic vaccination of HHD mice with PAP-3 led to rejection of early established tumors and to increase of mouse survival. These results strongly support a therapeutic relevance of the identified CTL epitope upon active antitumor immunization. The newly established carcinoma model presented herein might be a useful tool for cancer vaccine design and optimization.

Topics: Acid Phosphatase; Animals; Cancer Vaccines; Carcinoma, Lewis Lung; Epitopes, T-Lymphocyte; HLA-A Antigens; HLA-A2 Antigen; Humans; Immunotherapy; Lymphokines; Male; Mice; Mice, Transgenic; Microscopy, Confocal; Polymerase Chain Reaction; Prostatic Neoplasms; Protein Tyrosine Phosphatases; Sialoglycoproteins

Prostatic acid phosphatase (PAP) is a prostate cancer tumor antigen and a prostate-specific protein shared by rats and humans. Previous studies indicated that Copenhagen rats immunized with a recombinant vaccinia virus expressing human PAP (hPAP) developed PAP-specific cytotoxic T cells (CTL) with cross reactivity to rat PAP (rPAP) and evidence of prostate inflammation. Viral delivery of vaccine antigens is an active area of clinical investigation. However, a potential difficulty with viral-based immunizations is that immune responses elicited to the viral vector might limit the possibility of multiple immunizations. In this paper, we investigate the ability of another genetic immunization method, a DNA vaccine encoding PAP, to elicit antigen-specific CD8+ T cell immune responses. Specifically, Lewis rats were immunized with either a plasmid DNA-based (pTVG-HP) or vaccinia-based (VV-HP) vaccine each encoding hPAP. We determined that rats immunized with a DNA vaccine encoding hPAP developed a Th1-biased immune response as indicated by proliferating PAP-specific CD4+ and CD8+ cells and IFNgamma production. Rats immunized with vaccinia virus encoding PAP did not develop a PAP-specific response unless boosted with a heterologous vaccination scheme. Most importantly, multiple immunizations with a DNA vaccine encoding the rat PAP homologue (pTVG-RP) could overcome peripheral self-tolerance against rPAP and generate a Th1-biased antigen-specific CD4+ and CD8+ T cell response. Overall, DNA vaccines provide a safe and effective method of generating prostate antigen-specific T cell responses. These findings support the investigation of PAP-specific DNA vaccines in human clinical trials.

Topics: Acid Phosphatase; Animals; Autoantigens; Cancer Vaccines; CD8-Positive T-Lymphocytes; Enzyme-Linked Immunosorbent Assay; Flow Cytometry; Genetic Vectors; Humans; Male; Plasmids; Prostatic Neoplasms; Protein Tyrosine Phosphatases; Rats; Rats, Inbred Lew; Transduction, Genetic; Vaccines, DNA; Vaccinia virus

We previously reported that several DNA fragments from human prostate-specific membrane antigen (hPSM), mouse prostatic acid phosphatase (mPAP), and human prostate-specific antigen (hPSA) genes were selected and fused to create a novel hPSM-mPAP-hPSA fusion gene (named 3P gene), and human secondary lymphoid tissue chemokine (SLC), 3P, and human IgG Fc genes were inserted into pcDNA3.1 to construct a DNA vaccine, designated pSLC-3P-Fc. In this report, to establish a more efficient treatment for immunotherapy against prostate cancer, the construct was transfected into B16F10 to generate gene-modified tumor cell vaccine (named B16F10-SLC-3P-Fc). In poorly immunogenic B16F10 mouse melanoma model, the immunization with B16F10-SLC-3P-Fc resulted in a strong antitumor response and 50% of tumor-bearing mice achieved long-term survival (>120 days). In vivo depletion of lymphocytes indicated that CD8(+) T cells were involved in the direct tumor killing, whereas CD4(+) T lymphocytes were required for the induction of CD8(+) CTL response in B16F10-SLC-3P-Fc-immunized mice. Splenocytes from B16F10-SLC-3P-Fc-immunized mice specifically recognized and lysed PSM, PAP, PSA, and 3P expressing tumor cells. The combined therapy of B16F10-SLC-3P-Fc plus anti-B7-H1 MAbs further enhanced the immune response. Rechallenge experiment showed that a persistent memory response was successfully induced by the combined therapy. These observations suggest pSLC-3P-Fc-modified tumor cells could serve as a vaccine against prostate cancer, and the therapy combined with anti-B7-H1 MAbs further enhanced the antitumor immune response.

Topics: Acid Phosphatase; Animals; Antigen Presentation; Antigens, CD; Antigens, Neoplasm; Antigens, Surface; B7-H1 Antigen; Cancer Vaccines; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Chemokines; Chemotaxis, Leukocyte; Cytotoxicity, Immunologic; Dendritic Cells; Humans; Immunotherapy; Injections, Subcutaneous; Male; Mice; Mice, Inbred C57BL; Prostate-Specific Antigen; Prostatic Neoplasms; Protein Tyrosine Phosphatases; Survival Rate; Tumor Cells, Cultured; Vaccines, DNA

We are developing a noninvasive approach for targeting imaging and therapeutic radionuclides to prostate cancer. Our method, Enzyme-Mediated Cancer Imaging and Therapy (EMCIT), aims to use enzyme-dependent, site-specific, in vivo precipitation of a radioactive molecule within the extracellular space of solid tumors. Advanced methods for data mining of the literature, protein databases, and knowledge bases (IT. Omics LSGraph and Ingenuity Systems) identified prostatic acid phosphatase (PAP) as an enzyme overexpressed in prostate cancer and secreted in the extracellular space. Using AutoDock 3.0 software, the prodrug ammonium 2-(2'-phosphoryloxyphenyl)-6-iodo-4-(3H)-quinazolinone (IQ(2-P)) was docked in silico into the X-ray structure of PAP. The data indicate that IQ(2-P) docked into the PAP active site with a calculated inhibition constant (K(i)) more favorable than that of the PAP inhibitor alpha-benzylaminobenzylphosphonic acid. When (125)IQ(2-P), the radioiodinated form of the water-soluble prodrug, was incubated with PAP, rapid hydrolysis of the compound was observed as exemplified by formation of the water-insoluble 2-(2'-hydroxyphenyl)-6-[(125)I]iodo-4-(3H)-quinazolinone ((125)IQ(2-OH)). Similarly, the incubation of IQ(2-P) with human LNCaP, PC-3, and 22Rv1 prostate tumor cells resulted in the formation of large fluorescent IQ(2-OH) crystals. No hydrolysis was seen in the presence of normal human cells. Autoradiography of tumor cells incubated with (125)IQ(2-P) showed accumulation of radioactive grains ((125)IQ(2-OH)) around the cells. We anticipate that the EMCIT approach will enable the active in vivo entrapment of radioimaging and radiotherapeutic compounds within the extracellular spaces of primary prostate tumors and their metastases.

Topics: Acid Phosphatase; Carcinoma; Computer Simulation; Drug Delivery Systems; Extracellular Space; Humans; Iodine Radioisotopes; Male; Models, Biological; Models, Molecular; Prodrugs; Prostatic Neoplasms; Protein Tyrosine Phosphatases; Quaternary Ammonium Compounds; Quinazolinones; Tumor Cells, Cultured

The crucial role of CD4 T-cells in anti-tumor immune response is widely recognized, yet the identification of HLA class II-restricted epitopes derived from tumor antigens has lagged behind compared to class I epitopes. This is particularly true for prostate cancer. Based on the hypothesis that successful cancer immunotherapy will likely resemble autoimmunity, we searched for the CD4 T-cell epitopes derived from prostatic proteins that are restricted by human leukocyte antigen (HLA)-DRB1*1501, an allele associated with granulomatous prostatitis (GP), a disease that may have an autoimmune etiology. One of the antigens implicated in the development of autoimmunity in the prostate is prostatic acid phosphatase (PAP), which is also considered a promising target for prostate cancer immunotherapy.. We immunized transgenic (tg) mice engineered to express HLA-DRB1*1501 with human PAP. A library of overlapping 20-mer peptides spanning the entire human PAP sequence was screened in vitro for T-cell recognition by proliferative and interferon (IFN)-gamma enzyme-linked immunosorbent spot (ELISPOT) assays.. We identified two 20-mer peptides, PAP (133-152), and PAP (173-192), that were immunogenic and naturally processed from whole PAP in HLA-DRB1*1501 tg mice. These peptides were also capable of stimulating CD4 T lymphocytes from HLA-DRB1*1501-positive patients with GP and normal donors.. These peptides can be used for the design of a new generation of peptide-based vaccines against prostate cancer. The study can also be helpful in understanding the role of autoimmunity in the development of some forms of chronic prostatitis.

Topics: Acid Phosphatase; Alleles; Amino Acid Sequence; Animals; Cancer Vaccines; CD4-Positive T-Lymphocytes; Cells, Cultured; Epitopes; HLA-DR Antigens; HLA-DR2 Antigen; HLA-DRB1 Chains; Humans; Male; Mice; Mice, Transgenic; Molecular Sequence Data; Peptides; Prostatic Neoplasms; Prostatitis; Protein Tyrosine Phosphatases

Abnormal differentiation in epithelial stem cells or their immediate proliferative progeny, the transiently amplifying population (TAP), may explain malignant pathogenesis in the human prostate. These models are of particular importance as differing sensitivities to androgen among epithelial cell subpopulations during differentiation are recognised and may account for progression to androgen independent prostate cancer. Androgens are crucial in driving terminal differentiation and their indirect effects via growth factors from adjacent androgen responsive stroma are becoming better characterised. However, direct effects of androgen on immature cells in the context of a prostate stem cell model have not been investigated in detail and are studied in this work. In alpha2beta1hi stem cell enriched basal cells, androgen analogue R1881 directly promoted differentiation by the induction of differentiation-specific markers CK18, androgen receptor (AR), PSA and PAP. Furthermore, treatment with androgen down-regulated alpha2beta1 integrin expression, which is implicated in the maintenance of the immature basal cell phenotype. The alpha2beta1hi cells were previously demonstrated to lack AR expression and the direct effects of androgen were confirmed by inhibition using the anti-androgen bicalutamide. AR protein expression in alpha2beta1hi cells became detectable when its degradation was repressed by the proteosomal inhibitor MG132. Stratifying the alpha2beta1hi cells into stem (CD133(+)) and transient amplifying population (TAP) (CD133(-)) subpopulations, AR mRNA expression was found to be restricted to the CD133(-) (TAP) cells. The presence of a functional AR in the TAP, an androgen independent subpopulation for survival, may have particular clinical significance in hormone resistant prostate cancer, where both the selection of immature cells and functioning AR regulated pathways are involved.

Topics: AC133 Antigen; Acid Phosphatase; Aged; Aged, 80 and over; Androgen Antagonists; Anilides; Antigens, CD; Cell Differentiation; Cell Proliferation; Cell Transformation, Neoplastic; Cells, Cultured; Cysteine Proteinase Inhibitors; Dose-Response Relationship, Drug; Epithelial Cells; Fibroblast Growth Factor 7; Glycoproteins; Humans; Integrin alpha2beta1; Keratin-18; Leupeptins; Male; Metribolone; Middle Aged; Neoplastic Stem Cells; Nitriles; Peptides; Phenotype; Prostate-Specific Antigen; Prostatic Neoplasms; Proteasome Endopeptidase Complex; Proteasome Inhibitors; Protein Tyrosine Phosphatases; Receptors, Androgen; RNA, Messenger; Signal Transduction; Testosterone Congeners; Tosyl Compounds

Prostatic urothelial-type adenocarcinoma arises through a process of glandular metaplasia of the prostatic urethral urothelium and subsequent in situ adenocarcinoma sometimes associated with villous adenoma. These prostatic adenocarcinomas are analogous to nonurachal adenocarcinomas arising in the bladder from cystitis glandularis. Only 2 cases of urothelial-type adenocarcinoma from an institution other than our own have been previously described. The distinction between adenocarcinoma from another organ secondarily involving the prostate, usual adenocarcinoma of the prostate, and prostatic urothelial-type adenocarcinoma can present a significant diagnostic challenge and has significant therapeutic implications. Fifteen cases of prostatic urothelial-type adenocarcinoma were retrieved from the consult files of one of the authors. Mean patient age at diagnosis was 72 years (range 58 to 93 y). All men had negative colonoscopies, clinically excluding a colonic primary. Bladder primaries were ruled out clinically or pathologically in radical resection specimens. Follow-up was available on all men with a mean of 50.3 months (range 2 to 161 mo). All men presented with urinary obstruction symptoms with 3 (20%) also having mucusuria and 2 (13.3%) also having hematuria. Four men (26.7%) developed metastatic disease and 8 (53.3%) died of disease. In 8/15 (53%) cases, glandular metaplasia of the prostatic urethra and contiguous transition to adenocarcinoma were identified. Multiple histologic patterns were observed including dissection of the stroma by mucin pools 15/15 (100%), villous features 7/15 (47%), necrosis 2/15 (13.3%), signet ring cells 3/15 (20%), perineural invasion 1/15 (6.7%), focal squamous differentiation 1/15 (6.7%), and a granulomatous inflammatory response 1/15 (6.7%). Immunohistochemical stains were negative for prostate specific antigen, prostate specific acid phosphatase, CDX2, and beta-catenin in all cases. Stains were positive for high molecular weight cytokeratin in 12/12 cases (100%), and CK7 and CK20 in 10/12 cases (83.3%). Prostatic urothelial-type adenocarcinoma is a rare aggressive cancer arising in the prostate. The differential diagnosis includes conventional prostatic mucinous adenocarcinoma and secondary infiltration from a colonic or bladder adenocarcinoma. Immunohistochemistry for prostate specific antigen, prostate specific acid phosphatase, and high molecular weight cytokeratin along with morphology can help rule out conventional

Topics: Acid Phosphatase; Adenocarcinoma; Adenocarcinoma, Mucinous; Aged; Aged, 80 and over; beta Catenin; CDX2 Transcription Factor; Cell Differentiation; Diagnosis, Differential; Follow-Up Studies; Homeodomain Proteins; Humans; Immunohistochemistry; Keratin-20; Keratin-7; Male; Middle Aged; Mucins; Neoplasm Invasiveness; Prognosis; Prostate-Specific Antigen; Prostatic Neoplasms; Protein Tyrosine Phosphatases; Time Factors; Urothelium

Novel prognostic indexes clinically applicable for patients with Stage IV prostate cancer are needed because prostate-specific antigen (PSA) tests occasionally fail to reflect the prognostic outcome. We investigated various clinicopathologic parameters in men with Stage IV prostate cancer and evaluated the utility of the PSA/prostatic acid phosphatase (PAP) ratio as a prognostic index.. We reviewed 241 patients with Stage IV prostate cancer, who were treated in Niigata Cancer Center Hospital from 1992 to 2004. Survival curves were generated using the Kaplan-Meier method. Univariate and multivariate analyses of survival associations, including age, performance status, clinical presentation, disease localization, pathologic findings, and serologic markers, were conducted using the log-rank test and Cox proportional hazard models.. The 5-year overall survival rate using the Kaplan-Meier method for all 241 patients was 43.0%. No significant difference was found in the survival rates according to PSA level. However, the 5-year survival rate was significantly lower in patients with a PSA/PAP ratio of less than 3.0 (P = 0.0022): 24.2% and 48.0% in those with a PSA/PAP ratio of less than 3.0 and 3.0 or greater, respectively. On multivariate analysis using the proportional hazards model, the statistically significant prognostic factors of overall survival were alkaline phosphatase (P = 0.0413), lactate dehydrogenase (P = 0.0409), and the PSA/PAP ratio (P = 0.0113).. The PSA/PAP ratio is a valuable prognostic indicator in men with Stage IV prostate cancer. Although our study found that other laboratory tests also had a prognostic influence, the PSA/PAP ratio was an essential index implicated in the physiopathology of prostate cancer.

Topics: Acid Phosphatase; Aged; Aged, 80 and over; Alkaline Phosphatase; Biomarkers, Tumor; Bone Neoplasms; Hemoglobins; Humans; Kaplan-Meier Estimate; L-Lactate Dehydrogenase; Male; Middle Aged; Prognosis; Prostate-Specific Antigen; Prostatic Neoplasms; Protein Tyrosine Phosphatases; Survival Rate

Activation of immune defense mechanisms against tumor antigens appears to be a promising therapeutic option for advanced prostate cancer (PCa). Specific immunotherapy critically depends on target antigens that are selectively expressed in the tumorous and optional in the normal prostate tissue in sufficient amounts. Although several prostate antigens have been described and some have already been used in clinical trials, a detailed comparative evaluation of their tissue-specificity and expression levels is still lacking. We determined the transcript levels of eight prostate targets (PSA, PAP, PSCA, PSGR, Prostein, PSMA, AIbZIP, trp-p8) in 16 different tissues by quantitative PCR and calculated a tissue-specificity index (TSI) for each molecule. Besides a preferential expression in prostate for all targets, striking differences in the expression levels and TSI were revealed which may be important for the selection of appropriate antigens for immunotherapy of PCa.

Topics: Acid Phosphatase; Antigens, Neoplasm; Antigens, Surface; Basic-Leucine Zipper Transcription Factors; Cyclic AMP Response Element-Binding Protein; Gene Expression; Glutamate Carboxypeptidase II; GPI-Linked Proteins; Humans; Immunotherapy; Male; Membrane Glycoproteins; Membrane Proteins; Neoplasm Proteins; Nuclear Proteins; Organ Specificity; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Protein Tyrosine Phosphatases; Receptors, Odorant; RNA, Messenger; TRPM Cation Channels

Prostatic acid phosphatase (PAP) is a prostate tumor antigen currently being investigated as a target antigen in several human vaccine trials, some with evidence of clinical benefit. We have previously demonstrated that plasmid DNA vaccines encoding either human or rat PAP can elicit antigen-specific cellular and humoral immunity in rat models. The current study was performed to determine the safety and potential immunological efficacy in rodents of large and repetitive doses of a GMP-grade plasmid DNA vaccine encoding human PAP, pTVG-HP. Fifty-four male Lewis rats were immunized intradermally at 2-week intervals with 100, 500, or 1,500 microg pTVG-HP with 5 microg recombinant rat GM-CSF protein given as a vaccine adjuvant. An additional 12 male Lewis rats served as controls with groups immunized with 1,500 microg of a parental DNA vector not encoding human PAP, and a group that received GM-CSF protein only without plasmid DNA. Groups of animals (n=3-6) were euthanized after two, four, or six immunizations with collections of tissues and blood for toxicity assessment and immunological analysis. No significant toxicities were observed in terms of animal weights, histopathology, hematological changes, or changes in serum chemistries. Six of fifty-four were found to have subtle evidence of possible renal toxicity, however these findings were not statistically different from control animals. The vaccine was found to be effective in eliciting PAP-specific CD4 and CD8 T cells, predominantly Th1 in type, in all immunized animals at all doses and numbers of immunizations. PAP-specific IgG were detected in a dose-dependent fashion, with titers increasing after multiple immunizations. These studies demonstrate that, in rats, immunization with the pTVG-HP vaccine is safe and effective in eliciting PAP-specific cellular and humoral immune responses. These findings support the further clinical evaluation of pTVG-HP in patients with prostate cancer.

Topics: Acid Phosphatase; Animals; Antibody Formation; Cancer Vaccines; Enzyme-Linked Immunosorbent Assay; Immunity, Cellular; Immunoglobulin G; Male; Plasmids; Prostate; Prostatic Neoplasms; Rats; Rats, Inbred Lew; Spleen; T-Lymphocytes; Vaccines, DNA

DNA vaccines provide an attractive technology against cancer because of their safety record in humans and ease of construction, testing and manufacture. In this study, several DNA fragments encoding multiple cytotoxic T lymphocyte (CTL) and T helper cell epitopes were selected from human prostate-specific membrane antigen (hPSM), mouse prostatic acid phosphatase (mPAP), and human prostate-specific antigen (hPSA). These DNA fragments were ligated together to form a novel fusion gene, termed the 3P gene. The secondary lymphoid tissue chemokine (SLC), 3P and human immunoglobulin G Fc genes were inserted into pcDNA3.1 to construct a DNA vaccine, designated pSLC-3P-Fc. After vaccination, the DNA is taken up by cells that produce and secrete the SLC-3P-Fc fusion proteins, termed chemotactic antigen (chemo-antigen). The secreted chemo-antigens, in addition to promoting the co-localization of naive, non-polarized memory T cells and dendritic cells, are efficiently captured and processed by dendritic cells via receptor-mediated endocytosis and then cross-presented to both major histocompatibility complex class I and class II in a cognate manner. The results of this study demonstrate that vaccination with pSLC-3P-Fc by gene gun inoculation induced a strong antitumour response in a mouse tumour model, which significantly inhibited tumour growth and prolonged the survival time of the tumour-bearing mice. In vitro, the secreted SLC-3P-Fc fusion protein can attract lymphocytes from human peripheral blood mononuclear cells (PBMC); when human lymphocytes were stimulated by pSLC-3P-Fc-transfected autologous PBMC, CTLs were induced which could specifically kill hPSM-, hPAP-, or hPSA-expressing tumour cells. These observations provide a new vaccine strategy for cancer therapy through promoting the co-localization of lymphocytes and the concomitant enhancement of antigen-specific CD4+ helper and CD8+ cytotoxic T-cell responses against tumour.

Topics: Acid Phosphatase; Animals; Antigen Presentation; Antigens, Neoplasm; Antigens, Surface; Biolistics; Blotting, Western; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Chemokines; Chemotaxis, Leukocyte; Cytotoxicity, Immunologic; Dendritic Cells; Epitopes, T-Lymphocyte; Glutamate Carboxypeptidase II; Male; Mice; Mice, Inbred C57BL; Prostate-Specific Antigen; Prostatic Neoplasms; Protein Tyrosine Phosphatases; Survival Rate; Transfection; Tumor Cells, Cultured; Vaccines, DNA

To evaluate the significance of prostatic acid phosphatase (PAP), we analyzed 1,029 prostate cancer patients who were treated at the Niigata Cancer Center. We classified clinically localized prostate cancer with elevated PAP as stage DO. When stage DO was not taken into acount, the 5-year cause-specific survival rate for stage A, B, C and D was 94.7, 97.9, 87.7 and 42.4%, respectively. Taking stage DO into account, the cause-specific survival curve for stage DO patients was similar to those for stage B,C patients. The 5-year cause-specific survival rate for stage DO was 92.2% considering above 3 ng/ml as elevated PAP. A significant correlation was found between PAP and cause-specific survival for all cases but no correlation was found for non-metastatic disease patients. The significance of PAP in the staging of prostate cancer is limited.

Topics: Acid Phosphatase; Adenocarcinoma; Aged; Aged, 80 and over; Humans; Male; Middle Aged; Prognosis; Prostatic Neoplasms; Protein Tyrosine Phosphatases; Survival Analysis

Neuroendocrine (NE) cells increase in high grade/stage prostate cancer (PC) and may contribute to androgen-independent cancer. Their immunohistochemical phenotype has not been studied in detail and conflicting results have been reported.. PC tissue was stained immunohistochemically for luminal secretory cell-associated cytokeratin, basal cell markers, ki-67, androgen receptor (AR), PSA, prostate acid phosphatase (PAP), and alpha-methylacyl coenzyme A racemase (AMACR).. The NE cells are positive for AE1/AE3, Cam 5.2, and negative for basal cell markers. They are negative for AR, PSA, and Ki-67 but positive for PAP. The benign NE cells are negative for AMACR while the malignant NE cells are positive for AMACR.. NE cells of PC constitute a unique subset of cancer cells, which have a unique immunohistochemical profile. They do not express AR, consistent with their resistance to hormonal therapy. They are post-mitotic cells but are malignant and part of the tumor.

Topics: Acid Phosphatase; Androgen Antagonists; Drug Resistance, Neoplasm; Gene Expression Regulation, Neoplastic; Humans; Immunohistochemistry; Keratins; Ki-67 Antigen; Male; Neuroendocrine Tumors; Phenotype; Prostate-Specific Antigen; Prostatic Neoplasms; Racemases and Epimerases; Receptors, Androgen

We retrospectively reviewed the cytologic features of metastatic prostatic ductal carcinoma (PDC) in 23 cases, clinical manifestations, and clinical outcomes. Cytologic smears typically showed tumor cells with abundant cytoplasm and oval nuclei arranged in papillary groups or flat and folded sheets, some of which showed peripheral nuclear palisading. However, these features could be focal, subtle, and even indistinguishable from those of acinar carcinoma, particularly when the ductal component was predominantly of a cribriform and solid pattern or coexisted with acinar carcinoma. A determination of a prostatic origin of a metastatic PDC, based on cytomorphologic features alone, could be difficult. Immunostaining for prostate-specific antigen and prostatic acid phosphatase proved helpful in determining a definitive diagnosis. The median followup of patients was 82 months, the median overall survival was 77 months, and the 5-year overall survival rate was 72%. Tumor growth pattern did not correlate with prognosis, but visceral metastasis conveyed a poor prognosis. The correlation with clinical and radiologic findings, a high index of suspicion, and the use of immunoperoxidase studies are important in making an accurate diagnosis.

Topics: Acid Phosphatase; Aged; Biomarkers, Tumor; Biopsy, Needle; Carcinoma, Ductal; Humans; Immunoenzyme Techniques; Male; Middle Aged; Prognosis; Prostate-Specific Antigen; Prostatic Neoplasms; Protein Tyrosine Phosphatases; Retrospective Studies; Survival Rate

Precursors of prostate-specific antigen (proPSA) have been previously shown to be more concentrated in prostate cancer tissue. This study characterizes the immunohistochemical staining (IHS) of proPSA forms in metastatic prostate cancer compared with prostate specific antigen (PSA) and prostatic acid phosphatase (PAP). A tissue microarray, consisting of 74 cases of metastatic prostate carcinoma and control tissues, was used. IHS, using monoclonal antibodies against proPSA with a truncated proleader peptide containing 2 amino acids ([-2]pPSA), native ([-5/-7]pPSA), PSA, and PAP, was analyzed. The monoclonal antibodies were specific for both benign and malignant prostatic glandular tissue. IHS with [-5/-7]pPSA showed the least number of cases with negative staining (3%), and the most number of cases with moderate or strong staining (76%). In the 60 cases where all 4 stains could be evaluated, none of them were negative for proPSA and positive for PSA or PAP, and all 7 cases that were negative for both PSA and PAP showed IHS to proPSA. [-5/-7]pPSA (native proPSA) may be a better marker than PSA and PAP in characterizing metastatic prostate adenocarcinoma, with most of the cases showing positivity for the marker. Even cases that were negative for PSA and PAP, were reactive for proPSA. Such enhanced detection is particularly important in poorly differentiated carcinomas involving metastatic sites where prostate carcinoma is a consideration. A panel of markers, including proPSA, should be performed when metastatic prostate carcinoma is in the differential diagnosis.

Topics: Acid Phosphatase; Adenocarcinoma; Biomarkers, Tumor; Humans; Immunoenzyme Techniques; Male; Prostate-Specific Antigen; Prostatic Neoplasms; Protein Precursors; Protein Tyrosine Phosphatases; Tissue Array Analysis

Thrombospondin-1 (TSP-1) is a multifunctional matricellular glycoprotein involved in several mechanisms critical to the formation and progression of solid tumors including cell adhesion, proliferation, migration, invasion, and angiogenesis. However, work related to TSP-1 expression and functionality in prostate cancer is limited. Expression experiments in the present study demonstrated lower expression of TSP-1 in the prostate cancer cell lines DU 145 and LNCaP compared to SV40-immortalized prostatic epithelial cells PNT 1A. All three cell lines expressed the TSP-1 receptor CD36. Exogenously added TSP-1 modulated the cellular phenotype of LNCaP cells, which demonstrated decreased proliferation rate and partly entered apoptosis. Collectively, these data support the concept that partial or complete loss of TSP-1 synthesis may provide tumor cells with a proliferation advantage. In addition, TSP-1 located at the border between tumor and stroma as observed in primary prostate tumors may act as a barrier of tumor growth depending on the TSP-1 receptor repertoire of the tumor cells.

Topics: Acid Phosphatase; Apoptosis; Blood Platelets; CD36 Antigens; Cell Line; Cell Line, Tumor; Cell Proliferation; Flow Cytometry; Humans; Male; Microscopy, Electron, Transmission; Prostate; Prostatic Neoplasms; Thrombin; Thrombospondin 1

Bone metastasis is a common untreatable complication associated with prostate cancer. Metastatic cells seed in skeletal sites under active turnover containing dense marrow cellularity. We hypothesized that differences in these skeletal-specific processes are among the critical factors that facilitate the preferential localization of metastatic prostate cancer in bone. To test this, athymic mice were administered PTH to induce bone turnover and increase marrow cellularity daily 1 wk before and after intracardiac inoculation of luciferase-tagged PC-3 cells. Tumor localization was monitored by bioluminescence imaging weekly for 5 wk. At the time of tumor inoculation, PTH-treated mice demonstrated significant increases in serum levels of bone turnover markers such as osteocalcin and tartrate-resistant acid phosphatase 5b and in the number of tartrate-resistant acid phosphatase-positive osteoclasts per millimeter of bone when compared with the other groups. Likewise, PTH treatment stimulated a qualitative increase in marrow cellular proliferation as determined by 5-bromo-2'-deoxyuridine immunostaining. Skeletal metastases formed in the hind limb and craniofacial regions of young mice with no difference between groups. In adult mice, however, bioluminescent signals in the hind limb and craniofacial regions were 3-fold higher in PTH-treated mice vs. controls. Fluorochrome labeling revealed increased bone formation activity in trabecular bone adjacent to tumors. When zoledronic acid, a nitrogen-containing bisphosphonate that inhibits osteoclast-mediated bone resorption, was administered concurrently with PTH, a significant reduction in the incidence of bone tumors was observed. Overall, these studies provide new evidence that skeletal sites rich in marrow cellularity under active turnover offer a more congenial microenvironment to facilitate cancer localization in the skeleton.

Topics: Acid Phosphatase; Animals; Bone Marrow Cells; Bone Neoplasms; Bone Remodeling; Bone Resorption; Cell Line, Tumor; Humans; Male; Mice; Osteocalcin; Osteogenesis; Parathyroid Hormone; Prostatic Neoplasms

The differential diagnosis of mucin-producing adenocarcinoma of the prostate includes conventional prostatic adenocarcinoma with mucin production, secondary adenocarcinoma usually of colorectal origin and, very rarely, urothelial-type adenocarcinoma arising from either the prostatic urethra or proximal ducts. Conventional prostatic adenocarcinoma with mucin production is readily identified by routine microscopy and immunohistochemistry. The distinction between secondary adenocarcinoma and urothelial-type adenocarcinoma, however, can present a significant diagnostic challenge. In addition, documented examples of the latter in the prostate are exceptionally rare. A transurethral resection of prostate specimen and prostatic needle biopsies from two patients showing urothelial-type adenocarcinoma of the prostate were identified in our consultation files. One of the patients subsequently underwent a radical prostatectomy. Both patients had negative gastrointestinal endoscopic workups. Transurethral resection of prostate material from two patients with clinically confirmed secondary adenocarcinoma of colonic origin involving the prostate and a prostatectomy specimen with mucinous conventional prostatic adenocarcinoma were also identified for comparison purposes. Formalin-fixed, paraffin-embedded sections were stained for prostate-specific antigen (PSA), prostatic acid phosphatase, carcinoembryonic antigen, cytokeratin 7, cytokeratin 20 and high molecular weight cytokeratin 34betaE12. The urothelial-type adenocarcinoma cases were diffusely positive for cytokeratin 7 and focally positive for 34betaE12 and cytokeratin 20, consistent with an origin from the urothelium of the prostatic urethra or proximal prostatic ducts. In contrast, the secondary adenocarcinoma of colonic origin cases were diffusely cytokeratin 20 positive and either negative or focally positive for cytokeratin 7 and negative for 34betaE12. The mucinous conventional prostatic adenocarcinoma was positive for PSA and prostatic acid phosphatase and negative for cytokeratin 7, cytokeratin 20 and 34betaE12. All tumors were positive for carcinoembryonic antigen.

Topics: Acid Phosphatase; Adenocarcinoma, Mucinous; Aged; Aged, 80 and over; Carcinoembryonic Antigen; Carcinoma, Transitional Cell; Diagnosis, Differential; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Male; Middle Aged; Prostate-Specific Antigen; Prostatic Neoplasms; Protein Tyrosine Phosphatases

Topics: Acid Phosphatase; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Bevacizumab; Bridged-Ring Compounds; Clinical Trials as Topic; Dendritic Cells; Humans; Immunotherapy; Male; Organometallic Compounds; Organophosphorus Compounds; Prostatic Neoplasms; Protein Tyrosine Phosphatases; Taxoids

We developed a rodent model that mimics the osteoblastic and osteolytic changes associated with human metastatic prostate cancer. Microarray analysis identified MMP-7, cathepsin-K, and apolipoprotein D as being upregulated at the tumor-bone interface. MMP-7, which was produced by osteoclasts at the tumor-bone interface, was capable of processing RANKL to a soluble form that promoted osteoclast activation. MMP-7-deficient mice demonstrated reduced prostate tumor-induced osteolysis and RANKL processing. This study suggests that inhibition of MMP-7 will have therapeutic benefit in the treatment of prostate cancer-induced osteolysis.

Topics: Acid Phosphatase; Actins; Animals; Carrier Proteins; Disease Models, Animal; Down-Regulation; Gene Expression; Gene Expression Profiling; Glycoproteins; Humans; Isoenzymes; Male; Matrix Metalloproteinase 7; Membrane Glycoproteins; Mice; Mice, Inbred C57BL; Mice, Knockout; Models, Biological; Monocytes; Osteoclasts; Osteolysis; Osteoprotegerin; Parathyroid Hormone-Related Protein; Prostatic Neoplasms; RANK Ligand; Rats; Rats, Inbred F344; Receptor Activator of Nuclear Factor-kappa B; Receptors, Cytoplasmic and Nuclear; Receptors, Tumor Necrosis Factor; Skull; Tartrate-Resistant Acid Phosphatase; Up-Regulation

Specific immunotherapy of prostate cancer may be an alternative or be complementary to other approaches for treatment of recurrent or metastasized disease. This study aims at identifying and characterizing prostate cancer-associated peptides capable of eliciting specific CTL responses in vivo. Evaluation of peptide-induced CTL activity in vitro was done following immunization of HLA-A2 transgenic (HHD) mice. An in vivo tumor rejection was tested by adoptive transfer of HHD immune lymphocytes to nude mice bearing human tumors. To confirm the existence of peptide-specific CTL precursors in human, lymphocytes from healthy and prostate cancer individuals were stimulated in vitro in the presence of these peptides and CTL activities were assayed. Two novel immunogenic peptides derived from overexpressed prostate antigens, prostatic acid phosphatase (PAP) and six-transmembrane epithelial antigen of prostate (STEAP), were identified; these peptides were designated PAP-3 and STEAP-3. Peptide-specific CTLs lysed HLA-A2.1+ LNCaP cells and inhibited tumor growth on adoptive immunotherapy. Furthermore, peptide-primed human lymphocytes derived from healthy and prostate cancer individuals lysed peptide-pulsed T2 cells and HLA-A2.1+ LNCaP cells. Based on the results presented herein, PAP-3 and STEAP-3 are naturally processed CTL epitopes possessing anti-prostate cancer reactivity in vivo and therefore may constitute vaccine candidates to be investigated in clinical trials.

Topics: Acid Phosphatase; Amino Acid Sequence; Animals; Antigens, Neoplasm; Cell Line, Tumor; Epitopes, T-Lymphocyte; HLA-A2 Antigen; Humans; Immunotherapy, Adoptive; Male; Mice; Mice, Knockout; Mice, Nude; Mice, Transgenic; Oxidoreductases; Peptide Fragments; Prostatic Neoplasms; Protein Tyrosine Phosphatases; T-Lymphocytes, Cytotoxic; Xenograft Model Antitumor Assays

We have previously shown that concentrations of 1alpha,25-dihydroxyvitamin D(3) (1,25D) that induce G(0)/G(1) cell cycle arrest in androgen-dependent LNCaP prostate cancer cells also decrease expression of c-Myc, a proto-oncogene that stimulates progression from G(1) to S phase of the cell cycle. Since both c-Myc expression and cell cycle progression are regulated by tyrosine kinase activation, we examined the ability of 1,25D to alter tyrosine kinase signaling in LNCaP cells and the androgen-independent LNCaP C81 (C81 LN) cell line. 1,25D selectively reduced protein tyrosine phosphorylation within both the LNCaP and C81 LN cells. This reduction in tyrosine kinase signaling appears to result from elevated levels of cellular prostatic acid phosphatase (PAcP). Western blots and biochemical assays revealed 1,25D increases the level of active PAcP in both cell lines. In addition, 1,25D decreased tyrosine phosphorylation of HER-2, an EGFR family member inactivated by PAcP, and the HER-2 downstream adaptor protein p52 Shc in C81 LN cells. Inhibition of HER-2 signaling by AG825 reduces growth of C81 LN cells and the parental LNCaP cells. These data therefore suggest that 1,25D-mediated decreases in LNCaP and C81 LN cell growth are in part due to decreases in tyrosine kinase signaling that result from up-regulation of PAcP.

Topics: Acid Phosphatase; Calcitriol; cdc25 Phosphatases; Cell Division; Cell Line, Tumor; Down-Regulation; Humans; Male; Oligopeptides; Phosphotyrosine; Prostatic Neoplasms; Protein Tyrosine Phosphatases; Proto-Oncogene Mas; Receptor, ErbB-2; Receptors, Calcitriol; Signal Transduction; Vitamin D

p66(Shc), an isoform of Shc adaptor proteins, is shown to mediate various signals, including cellular stress. However, little is known about its involvement in carcinogenesis. We previously showed that p66(Shc) protein level is upregulated by steroid hormones in human carcinoma cells and is higher in prostate cancer (PCa) specimens than adjacent noncancerous cells. In this study, we investigated the role of p66(Shc) protein in PCa cell proliferation. Among different PCa cell lines tested, p66(Shc) protein level showed positive correlation with cell proliferation, that is, rapid-growing cells expressed higher p66(Shc) protein than slow-growing cells. Exposure of slow-growing LNCaP C-33 cells to epidermal growth factor (EGF) and 5alpha-dihydrotestosterone (DHT) led to upregulation of proliferation and p66(Shc) protein level. Conversely, growth suppression of fast-growing cells by cellular form of prostatic acid phosphatase (cPAcP) expression, a negative growth regulator, down-regulated their p66(Shc) protein level. Additionally, increased expression of p66(Shc) protein by cDNA transfection in LNCaP C-33 cells resulted in increased cell proliferation. Cell cycle analyses showed higher percentage of p66(Shc)-overexpressing cells at S phase (24%) than control cells (17%), correlating with their growth rates. On the other hand, transient knock-down of p66(Shc) expression by RNAi in rapidly growing cells decreased their proliferation as evidenced by the reduced cell growth as well as S phase in p66(Shc)-knocked down cells. The p66(Shc) signaling in cell growth regulation is apparently mediated by extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK/MAPK). Thus, our results indicate a novel role for p66(Shc) in prostate carcinogenesis, in part, promoting cell proliferation.

Topics: Acid Phosphatase; Adaptor Proteins, Signal Transducing; Cell Line, Tumor; Cell Proliferation; Clone Cells; Dihydrotestosterone; Epidermal Growth Factor; Extracellular Signal-Regulated MAP Kinases; Gene Expression Regulation, Neoplastic; Humans; Male; Phosphorylation; Prostatic Neoplasms; Protein Isoforms; Protein Tyrosine Phosphatases; RNA Interference; S Phase; Shc Signaling Adaptor Proteins; Signal Transduction; Src Homology 2 Domain-Containing, Transforming Protein 1; Up-Regulation

The peptide vaccine candidates identified to date have been focused on the HLA-A2 and HLA-A24 alleles. The HLA-A11, HLA-A31, and HLA-A33 alleles share binding motifs and belong to an HLA-A3 supertype family. In this study, we attempted to identify CTL-directed peptide candidates, derived from prostate-related antigens and shared by HLA-A11+, HLA-A31+, and HLA-A33+ prostate cancer patients.. Based on the binding motif to the HLA-A3 supertype alleles, 42 peptides were prepared from prostate-specific antigen (PSA), prostate-specific membrane antigen (PSMA), and prostatic acid phosphatase (PAP). These peptides were first screened for their ability to be recognized by immunoglobulin G (IgG) of prostate cancer patients and subsequently for the potential to induce peptide-specific and prostate cancer-reactive CTLs from peripheral blood mononuclear cells (PBMC) of cancer patients with the HLA-A11, HLA-A31, and HLA-A33 alleles.. Five peptide candidates, including the PSA(16-24), PAP(155-163), PAP(248-257), PSMA(207-215), and PSMA(431-440) peptides, were frequently recognized by IgGs of prostate cancer patients. These peptides efficiently induced peptide-specific and prostate cancer-reactive CTLs from PBMCs of cancer patients with the HLA-A11, HLA-A31, and HLA-A33 alleles. Antibody blocking and cold inhibition experiments revealed that the HLA-A3 supertype-restricted cytotoxicity against prostate cancer cells could be ascribed to peptide-specific and CD8+ T cells.. We identified prostate-related antigen-derived new peptide candidates for HLA-A11-, HLA-A31-, and HLA-A33-positive prostate cancer patients. This information could facilitate the development of a peptide-based anticancer vaccine for patients with alleles other than HLA-A2 and HLA-A24.

Topics: Acid Phosphatase; Alleles; Amino Acid Motifs; Antigens, Surface; Cancer Vaccines; Cell Line, Tumor; Cold Temperature; Epitopes, T-Lymphocyte; Glutamate Carboxypeptidase II; HLA-A Antigens; HLA-A11 Antigen; HLA-A3 Antigen; Humans; Immunoglobulin G; Leukocytes, Mononuclear; Male; Peptides; Prostate-Specific Antigen; Prostatic Neoplasms; Protein Structure, Tertiary; Protein Tyrosine Phosphatases; T-Lymphocytes, Cytotoxic

Skeletal metastases are a significant problem in prostate cancer (PC). The patients are also exposed to treatment-related skeletal changes. This cross-sectional study evaluated a marker of bone resorption, TRACP 5b in relation to the standard analyte total alkaline phosphatase (tALP) as a marker of skeletal changes. Serum levels of TRACP 5b, tALP and PSA were measured in 130 prostate cancer patients. Comparison was made between patients with (BM+, n = 25) and without (BM-, n = 105) skeletal metastases, and between those treated with (n = 64) or without (n = 66) androgen deprivation (AD). Sensitivities and specificities were calculated for each marker and diagnostic accuracy was evaluated by ROC curve analysis. ROC curves indicated the superior accuracy of tALP, whereas TRACP 5b and PSA were comparable. With tALP the best combination of sensitivity (96%) and specificity of (91%) was reached at a cut-off point 224 U/L, the corresponding values were for TRACP 5b sensitivity (76%), specificity (89%) with a cut-off point 4.89 U/L, and for PSA sensitivity (65%), specificity (81%) at 23 ng/L for skeletal metastases. Patients treated with AD showed with increasing duration an increase in TRACP 5b values. TRACP 5b was less specific than tALP as a marker of skeletal metastases. TRACP 5b may have a role in the diagnostics of skeletal changes in PC with a focus on treatment-related skeletal changes.

Topics: Acid Phosphatase; Aged; Aged, 80 and over; Alkaline Phosphatase; Androgen Antagonists; Biomarkers, Tumor; Bone Neoplasms; Bone Resorption; Cross-Sectional Studies; Humans; Isoenzymes; Male; Middle Aged; Prostate-Specific Antigen; Prostatic Neoplasms; ROC Curve; Sensitivity and Specificity; Tartrate-Resistant Acid Phosphatase

We have previously developed methods for the quantification of different macromolecules in aspiration biopsy material and described the changes in prostate-specific antigen (T-PSA) during cancer treatment. We have now studied the changes in tissue prostatic acidic phosphatase (T-PAP) in 58 endocrine-treated patients with prostatic carcinoma and compared these data with cancer development data and tissue PSA (T-PSA) levels.. PAP and PSA were quantified in aspiration biopsies taken before treatment and after 6 and 12 months of treatment. Patients were followed until death or for >98 months.. Pretreatment T-PSA was more strongly associated with survival than T-PAP. Both T-PSA and T-PAP decreased in responders during treatment. In non-responders, T-PSA and T-PAP increased after 12 months in 17/18 and 7/13 patients, respectively. Estrogen-treated responders had significantly higher T-PSA, but not T-PAP, treatment values than those treated with orchidectomy or gonadotropin-releasing hormone.. The inferiority of serum PAP compared to PSA for monitoring cancer treatment may reflect its less pronounced changes at the tissue level, indicating different in vivo regulation of the two markers. Estrogen stimulation of PSA synthesis in vivo may underlie the higher PSA levels observed during estrogen treatment.

Topics: Acid Phosphatase; Aged; Aged, 80 and over; Biomarkers, Tumor; Biopsy, Needle; Carcinoma; Estrogens; Follow-Up Studies; Humans; Male; Middle Aged; Prognosis; Prostate-Specific Antigen; Prostatic Neoplasms; Protein Tyrosine Phosphatases; Retrospective Studies; Treatment Outcome

To study the immunophenotypic characteristics and clinical outcome of morphologically undifferentiated prostatic carcinoma with small-cell morphology (U-PC-SCM).. Sixteen patients with U-PC-SCM were enrolled. The streptavidin-biotin complex immunohistochemical method was used on paraffin-embedded tissue sections to test positivity for prostate-specific antigen, prostate-specific acid phosphatase, CD57, androgen receptors, CK8-18, epithelial membrane antigen, carcinoembryonic antigen, CD56, neuron-specific enolase, chromogranin, synaptophysin, serotonin, various hormones, thyroid transcriptional factor-1 and Ki-67/MIB1.. Based on immunophenotypic criteria, we identified two groups of patients. The final diagnosis was U-PC (Gleason score 10) in Group 1 (n=9) and pure or mixed neuroendocrine small-cell carcinoma in Group 2 (n=7). Group 1 underwent total androgen blockade (TAB) with no major response and had a median survival of 9 months. In Group 2, three patients underwent TAB, two of whom died of progressive disease. The third patient showed a partial response (PR) for 18 months but eventually relapsed with liver metastatic lesions. He was then treated with cisplatin + etoposide and showed a PR for 3 months and survived for 5 months after the initiation of the second-line chemotherapy (CTH) treatment. The other four patients received six cycles of cisplatin + etoposide. There were two complete responses of >14 and >22 months, respectively and 2 PRs of 11 and 17 months, respectively, the partial responders surviving for 14 and 21 months, respectively.. U-PC-SCM with a neuroendocrine immunophenotype is a histogenetically distinct entity with different clinical and laboratory manifestations which responds well to a cisplatin + etoposide CTH regimen.

Topics: Acid Phosphatase; Aged; Aged, 80 and over; Biomarkers, Tumor; Biopsy; Carcinoma, Small Cell; CD57 Antigens; Follow-Up Studies; Humans; Immunophenotyping; Male; Middle Aged; Neoplasm Staging; Prognosis; Prostate-Specific Antigen; Prostatic Neoplasms; Protein Tyrosine Phosphatases; Retrospective Studies

Topics: Acid Phosphatase; Biopsy, Needle; Ejaculatory Ducts; Humans; Male; Prostate-Specific Antigen; Prostatic Neoplasms; Seminal Vesicles

Only sporadic cases of prostate carcinomas with squamous differentiation have been reported.. The files of two institutions were reviewed for prostate cancers with squamous differentiation.. A total of 33 cases were studied. The average age at diagnosis was 68 years (range 49-86 years). The most common presenting symptoms included bladder outlet obstruction and dysuria. Thirteen men had a positive digital rectal examination. Diagnosis was made by needle biopsy (n = 23); transurethral resection of the prostate (n = 5); needle and transurethral resection of the prostate (n = 1); transurethral resection of the bladder (n = 1); or biopsy of metastases (n = 3). In 21 of 33 cases, there was a prior diagnosis of adenocarcinoma of the prostate; 8 patients were treated with hormones, 4 were treated with radiation, and 1 received both radiation and hormone therapy. Of the 12 men without a prior diagnosis of adenocarcinoma, 2 patients had received hormonal therapy for benign prostatic hyperplasia. Eight of 33 cases were pure squamous carcinomas. The remaining cases were adenosquamous carcinoma (n = 16), adenosquamous and urothelial carcinoma (n = 3), and adenosquamous carcinoma and sarcoma (n = 6). The squamous carcinoma component of these mixed cases averaged 40% of the tumor volume (range 5%-95%) and had a range of cytologic atypia (mild [n = 6], moderate [n = 17], severe [n = 10]). In the 25 cases with adenocarcinoma, the glandular component tended to be high-grade (Gleason grade >6 in 19 cases). Immunohistochemistry for prostate specific acid phosphatase and prostate specific antigen was positive in a large percentage of the adenocarcinomas (85% and 75%, respectively) and only very focally positive in 12% of the squamous carcinomas. 34 beta E12 was diffusely positive in >95% of the squamous carcinomas and only focally positive in <10% of the adenocarcinomas. Cytokeratins 7 and 20 did not differentiate the squamous and adenocarcinoma components. Follow-up was available on 25 of 33 cases, with the average survival being 24 months (range 0-63 months).. Squamous differentiation in prostate cancer is uncommon, often but not necessarily arising in the setting of prior hormone or radiation therapy, and is associated with a poor prognosis. In addition to pure squamous cell carcinoma and adenosquamous cancer, other patterns may be seen. Whereas the adenocarcinoma component is typically high grade, the squamous component has a wide range of differentiation.

Topics: Acid Phosphatase; Adenocarcinoma; Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoma, Squamous Cell; Cell Transformation, Neoplastic; Combined Modality Therapy; Humans; Immunohistochemistry; Male; Middle Aged; Neoplasms, Multiple Primary; Prostate-Specific Antigen; Prostatic Neoplasms; Protein Tyrosine Phosphatases; Survival Rate

Prostatic adenocarcinomas commonly exhibit neuroendocrine differentiation as demonstrated by immunohistochemistry. However, true carcinoids of the prostate are rare. We describe herein a case of a primary carcinoid occurring synchronously with a conventional adenocarcinoma in the prostate of a 66-year-old man. The carcinoid measured 0.2 x 0.2 cm and did not show contiguity with adjacent conventional, moderately differentiated adenocarcinoma. Immunohistochemical stains for chromogranin and neuron-specific enolase were strongly immunoreactive in the carcinoid but not in the adenocarcinoma. Both neoplasms demonstrated positive staining for prostatic acid phosphatase and prostate-specific antigen. Owing to the relatively minute size of the carcinoid, the possibility that this tumor will impact negatively on the patient's overall prognosis is not anticipated.

Topics: Acid Phosphatase; Adenocarcinoma; Aged; Biomarkers, Tumor; Carcinoid Tumor; Chromogranin A; Chromogranins; Disease-Free Survival; Humans; Immunoenzyme Techniques; Male; Neoplasms, Multiple Primary; Phosphopyruvate Hydratase; Prostate-Specific Antigen; Prostatic Neoplasms; Protein Tyrosine Phosphatases

To assess variations in prostate specific antigen (PSA) and prostate specific acid phosphatase (PSAP) immunohistochemistry with particular reference to the antibody type (monoclonal or polyclonal) and the tissues used for optimising immunostaining conditions and as external positive controls.. A questionnaire was sent to all laboratories registered with the UK National External Quality Assurance Scheme for immunohistochemistry enquiring about the immunohistochemical methods routinely used for the diagnosis of prostate cancer.. Responses were received from 220 (68%) laboratories. All UK respondents routinely performed PSA immunostaining but PSAP immunostaining was available in only 57% of these laboratories. Monoclonal anti-PSA, polyclonal anti-PSA, monoclonal anti-PSAP, and polyclonal anti-PSAP were used by 40%, 60%, 29%, and 27% of UK respondents, respectively. Benign prostate tissue was most commonly used to determine optimal antibody dilutions and as external quality control for PSA/PSAP, with only 6% and 3% of respondents, respectively, including high grade prostate cancer in the tissues used for these purposes.. The wide variation in the methods used highlights the need for standardisation and more stringent quality assurance of the immunohistochemical staining techniques used for PSA and PSAP. The widespread use of benign prostate tissue to determine optimal antibody dilutions and as an external positive control for PSA and PSAP immunostaining is of particular concern because this approach may result in a method that is not sufficiently sensitive to detect the reduced PSA and PSAP expression associated with high grade prostate cancer.

Topics: Acid Phosphatase; Biomarkers, Tumor; Europe; Humans; Immunohistochemistry; Male; Prostate-Specific Antigen; Prostatic Neoplasms; Quality Control; Reproducibility of Results; Surveys and Questionnaires; United Kingdom

Human prostatic acid phosphatase (PAcP) is a prostate epithelium-specific differentiation antigen. Cellular PAcP functions as a neutral protein tyrosine phosphatase and is involved in regulating androgen-promoted prostate cancer cell proliferation. Despite the fact that the promoter of the PAcP gene has been cloned, the transcriptional factors that regulate PAcP expression remain unidentified. This article describes our analyses of the promoter of the PAcP gene. Deletion analyses of the promoter sequence up to -4893 (-4893/+87) revealed that a 577 bp fragment (-1356/-779) represents the unique positive cis-active element in human prostate cancer cells but not in HeLa cervix carcinoma cells. Interestingly, the 577 bp fragment contains a non-consensus nuclear factor kappaB (NF-kappaB)-binding site that is required for NF-kappaB up-regulation in prostate cancer cells, while NF-kappaB failed to have the same effect in HeLa cells. Conversely, inhibition of the NF-kappaB pathway stopped p65 NF-kappaB activation of the p1356 promoter activity. Gel shift and mutation analyses determined that AGGTGT (-1254/-1249) is the core sequence for NF-kappaB-binding and activation. Biologically, tumor necrosis factor-alpha (TNF-alpha) activated endogenous PAcP expression in LNCaP human prostate cancer cells. The data collectively indicate that NF-kappaB up-regulates PAcP promoter activity via its binding to the AGGTGT motif, a novel binding sequence located inside the cis-active enhancer element in human prostate cancer cells.

Topics: 5' Flanking Region; Acid Phosphatase; Base Sequence; Binding Sites; Cell Line, Tumor; DNA Footprinting; Electrophoretic Mobility Shift Assay; Enhancer Elements, Genetic; Gene Expression Regulation, Neoplastic; Humans; I-kappa B Proteins; Interleukin-1; Male; Molecular Sequence Data; NF-kappa B; Oligonucleotides; Promoter Regions, Genetic; Prostate; Prostatic Neoplasms; Protein Tyrosine Phosphatases; Transcriptional Activation; Tumor Necrosis Factor-alpha

Topics: Acid Phosphatase; Autoimmunity; Cancer Vaccines; Controlled Clinical Trials as Topic; Dendritic Cells; Drug Industry; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Male; Placebos; Prostatic Neoplasms; Protein Tyrosine Phosphatases; Recombinant Fusion Proteins

Phyllodes tumor of the prostate is a rare neoplasm of uncertain malignant potential. We studied a large series of phyllodes tumors to define the combination of histological features that are most useful for predicting patient outcome.. A total of 23 cases were obtained from our collective files from 1973 to 2002, and numerous clinical and pathological features were evaluated. A review of the reported cases of phyllodes tumor of the prostate was done.. Patient age was 25 to 86 years (mean 55) and they usually presented with urinary obstructive symptoms and hematuria. The diagnosis was made in 18 tumors by transurethral resection, in 2 by enucleation, in 1 by tumor resection and in 2 by prostatectomy. We analyzed 5 histological features, including cellularity (scale of 1 to 3), cytologic atypia (scale of 1 to 3), the number of mitotic figures per 10 high power fields, the stroma-to-epithelium ratio (low or high) and necrosis (present or absent). This combination of features revealed that 14 cases were low grade phyllodes tumor, 7 were intermediate grade and 2 were high grade with the high grade cases characterized by increased cellularity, severe cytological atypia, more than 5 mitotic figures per 10 high power fields and a high stroma-to-epithelium ratio, indicating stromal overgrowth. Immunohistochemical studies of 8 tumors revealed consistent, intense cytoplasmic immunoreactivity in stromal cells for vimentin and actin, in luminal epithelial cells for prostate specific antigen, prostatic acid phosphatase and broad-spectrum keratin AE1/AE3, and in basal cells for high molecular weight keratin 34beta-E12. Recurrence was seen in 7 of 14 low grade tumors (50%) and in 1 patient low grade sarcoma emerged with subsequent distant metastases 14 years after initial diagnosis following 5 recurrences. Recurrence was seen in 6 of 7 intermediate grade tumors and low grade sarcoma emerged with subsequent abdominal wall metastases in 1 patient 11 years after initial diagnosis following 3 recurrences. The phyllodes tumor recurred in each patient with high grade tumors with a time to first recurrence of 6 and 0.2 years, respectively. Distant metastases developed in these 2 patients.. Histological grading of prostatic phyllodes tumors is predictive of short-term outcome based on the combination of stromal cellularity, cytological atypia, number of mitotic figures and the stroma-to-epithelium ratio. However, these tumors usually recur after transurethral prostatic resection and they are often locally aggressive with time. The emergence of overt sarcoma and metastatic disease is more frequent than previously recognized. Complete resection at initial diagnosis appears to be indicated.

Topics: Acid Phosphatase; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Follow-Up Studies; Humans; Immunohistochemistry; Male; Middle Aged; Neoplasm Recurrence, Local; Phyllodes Tumor; Prostate-Specific Antigen; Prostatic Neoplasms; Protein Tyrosine Phosphatases

Prostatic ductal adenocarcinoma represents a rare histological variant of prostatic carcinoma with features of a papillary lesion at cystoscopy. There are conflicts regarding the existence, origin, staging, grading, treatment and clinical behavior of this tumor. The aim of the present study is to examine the expression of Bcl-2 and p53 in prostatic ductal adenocarcinoma and to evaluate its origin by analyzing prostate specific antigen, prostate specific acid phosphatase, cytokeratins, epithelial membrane antigen and carcinoembryonic antigen expressions. The results confirmed the expression of prostate specific antigen and prostate specific acid phosphatase in prostatic ductal adenocarcinoma. The demonstrated expression of Bcl-2 was predominant in the better-differentiated tumor. Bcl-2 expression appears not to be associated with neuroendocrine differentiation as assessed by chromogranin A reactivity. Thus, the first case of a prostatic ductal adenocarcinoma showing Bcl-2 expression is presented. The tumor was negative for p53.

Topics: Acid Phosphatase; Aged; Aged, 80 and over; Carcinoma, Ductal; Chromogranin A; Chromogranins; Humans; Male; Prostate-Specific Antigen; Prostatic Neoplasms; Proto-Oncogene Proteins c-bcl-2; Tumor Suppressor Protein p53

Serum activity of tartrate-resistant acid phosphatase 5b (TRAP 5b) in patients with breast cancer and prostate cancer having bone metastases was much higher than in healthy donors and patients without skeletal injuries. TRAP 5b activity in patients with breast cancer and multiple bone metastases surpassed that in patients with single bone metastases. The mean activity of TRAP 5b and range of enzyme activity in women treated with bisphosphonates were significantly lower than in patients not receiving antiresorptive therapy. Diagnostic sensitivity and specificity of TRAP 5b as a marker of skeletal metastases in patients with breast cancer were 82 and 87%, respectively. In patients with prostate cancer these indexes were 71 and 83.4%, respectively. Detection of this marker in tumor patients holds much promise for early diagnostics of bone metastases, estimation of the severity of skeletal metastases, and monitoring of the efficiency of bisphosphonate therapy.

Topics: Acid Phosphatase; Adult; Aged; Antineoplastic Agents; Biomarkers; Biomarkers, Tumor; Bone Neoplasms; Bone Resorption; Breast Neoplasms; Case-Control Studies; Diphosphonates; Female; Humans; Isoenzymes; Male; Middle Aged; Neoplasm Metastasis; Prostatic Neoplasms; Sensitivity and Specificity; Tartrate-Resistant Acid Phosphatase

Topics: Acid Phosphatase; Adenocarcinoma; Aged; Aminoglutethimide; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Bone Neoplasms; Combined Modality Therapy; Fatal Outcome; Humans; Ketoconazole; Lymphatic Metastasis; Male; Neck; Neoplasm Proteins; Prednisone; Prostate-Specific Antigen; Prostatic Neoplasms

The expression and secretion of prostate-specific antigen (PSA) are regulated by androgens in normal prostate secretory epithelial cells. In prostate cancer patients, the serum PSA level is usually elevated and cancer cells are initially responsive to androgens. However, those cancer cells become androgen-independent after androgen ablation therapy. In hormone-refractory cancer patients, even in an androgen-deprived environment, the circulation level of PSA rebounds and is constitutively elevated through a yet unknown mechanism. Tyrosine phosphorylation of ErbB-2 is involved in regulating the androgen-responsive phenotype of prostate cancer cells, and it is at least partly regulated by the cellular form of prostatic acid phosphatase (PAcP), a prostate-unique protein tyrosine phosphatase. We investigated the ErbB-2 signal pathway in androgen-independent PSA secretion. LNCaP C-81 cells, which are androgen-independent LNCaP cells lacking endogenous PAcP expression with a hypertyrosine phosphorylated ErbB-2, secreted a higher level of PSA in conditioned media than did androgen-sensitive LNCaP C-33 parental cells. A restored expression of cellular PAcP in C-81 cells was concurrent with a decrease in tyrophosphorylation of ErbB-2 and reduction of PSA secretion. Moreover, transient transfection of C-33 cells with the wild-type ErbB-2 or a constitutively active mutant of MEK1 cDNA resulted in an increased level of secreted PSA. The elevation of secreted PSA level by the forced expression of ErbB-2 was inhibited by an MEK inhibitor, PD98059. In C-81 cells, the expression of a dominant negative mutant of ErbB-2 reduced the secreted level of PSA. The inhibition of ErbB-2 or mitogen-activated protein (MAP) kinases by specific inhibitors AG879, AG825, or PD98059 led to a decrease in PSA secretion. Taken together, our data clearly indicate that the ErbB-2 signal pathway via MAP kinases (ERK1/2) is involved in regulating the secretion of PSA by androgen-independent human prostate cancer LNCaP C-81 cells in an androgen-depleted environment.

Topics: Acid Phosphatase; Androgens; Cell Division; Culture Media, Conditioned; Humans; Male; MAP Kinase Kinase Kinase 1; Mitogen-Activated Protein Kinases; Prostate-Specific Antigen; Prostatic Neoplasms; Protein Serine-Threonine Kinases; Protein Tyrosine Phosphatases; Receptor, ErbB-2; Signal Transduction; Tumor Cells, Cultured; Up-Regulation

The objective of this study was to define the long-term prognostic significance of prostatic acid phosphatase (PAP) levels in patients with higher risk, early-stage prostate carcinoma.. One hundred sixty-one consecutive patients with Stage T1-T3 prostate carcinoma (according to the 1992 criteria of the American Joint Committee on Cancer) were treated from 1992 through 1996. Each patient had a Gleason score > or = 7 and/or a prostate specific antigen (PSA) level > 10 ng/mL. The original biopsy slides for 130 of 161 patients were retrieved and rereviewed by a single pathologist (L.T.). Enzymatic PAP measurements were determined using a standard method. Values up to 2.5 Units were considered normal. Patients received 41 grays (Gy) of external beam radiation therapy to a limited pelvic field followed 4 weeks later by a palladium 103 (Pd-103) boost using transrectal ultrasound and fluoroscopic guidance as described previously. The prescribed minimum Pd-103 dose to the prostate was 80 Gy (pre-National Institute of Standards and Technology [NIST]-99). Freedom from biochemical failure was defined as a serum PSA level < or =0.2 ng/mL at last follow-up.. There was little correlation between pretreatment PSA levels, Gleason scores, and PAP measurements. Thirty-eight patients developed biochemical failure. The overall actuarial freedom from biochemical progression at 10 years is 79%, with 118 patients followed for > 5 years. In a multivariate Cox proportional hazards analysis that considered each factor as a continuous variable, the strongest predictor of failure was PAP (P = 0.0001), followed by Gleason score (P = 0.13), and PSA (P = 0.04). PAP was especially helpful in stratifying patients with pretreatment PSA levels between 4 ng/mL and 20 ng/mL, for whom the prognosis does not different when they are subdivided into PSA categories. When the PAP subgroup analysis was limited to this relatively favorable group, there was a wide range of prognoses.. The biochemical cure rate was remarkably high among the 161 patients evaluated. The fact that the PAP was the strongest predictor of long-term biochemical failure in patients with otherwise higher risk features reported here suggests that it may be a more accurate indicator of micrometastatic disease compared with the Gleason score and the PSA level. This report adds to the rationale for reintroducing PAP measurement into general practice.

Topics: Acid Phosphatase; Aged; Biomarkers, Tumor; Brachytherapy; Carcinoma; Humans; Male; Middle Aged; Palladium; Prognosis; Prostatic Neoplasms; Protein Tyrosine Phosphatases; Radioisotopes; Time Factors; Treatment Outcome

Although the molecular mechanism of androgen-independent prostate cancer growth and progression has been gradually elucidated, there is limited effective treatment for this prevalent disease. Human prostatic acid phosphatase (PAcP), a major protein tyrosine phosphatase in prostate epithelium, plays a critical role in regulating the growth of prostate cancer cells. In prostate carcinomas, the expression of cellular PAcP decreases. To explore directly the possible therapeutic potential of cellular PAcP, we investigated the suppression effect of PAcP by utilizing cDNA direct intratumoral administration in androgen-independent LNCaP xenograft tumors.. An androgen-independent LNCaP cell model (C-33 and C-81 cells) and stable subclones of PAcP cDNA-transfected C-81 cells (LNCaP-23 and LNCaP-34 cells) were used for the experiments. We examined the growth property and expression of PAcP and c-ErbB-2 of these different LNCaP cells in vitro and in vivo. We subsequently investigated the growth suppression effect of PAcP cDNA intratumoral injection in pre-established C-81 xenograft tumors, and analyzed the expression of PAcP, prostate-specific antigen (PSA), proliferating cell nuclear antigen (PCNA), and c-ErbB-2 in the tumors by immunohistochemistry and Western blotting.. The different LNCaP cells exhibited different growth property and tumorigenicity, both in cell culture and xenograft. Biochemical characterizations revealed that the level of cellular PAcP correlated negatively with the growth property of different LNCaP cells, while the level of tyrophosphorylated c-ErbB-2 had an inverse correlation with cellular PAcP. The single intratumoral administration of the wild type PAcP cDNA showed a significant suppression effect on C-81 xenograft tumor growth, compared to vector alone-injected control (P<0.05). In the tumors injected with this PAcP cDNA, the PAcP expression was detected 1 week (wk) after injection, but was undetectable at 6 wk, which inversely correlated with the level of tyrophosphorylated c-ErbB-2 and the degree of cell proliferation indicated by PCNA staining.. Our results clearly demonstrated that cellular PAcP has a suppression effect on the growth of androgen-independent LNCaP xenograft tumors. This effect occurs at least partly through the dephosphorylation of c-ErbB-2 by PAcP, the prostate-specific protein tyrosine phosphatase. The data indicates that human PAcP could be utilized in the corrective gene therapy for a subgroup of androgen-independent human prostate cancer cells that lack cellular PAcP expression.

Topics: Acid Phosphatase; Animals; Cell Division; DNA; ErbB Receptors; Female; Genetic Therapy; Humans; Immunohistochemistry; Male; Mice; Mice, Inbred BALB C; Mice, Nude; Neoplasms, Hormone-Dependent; Phosphorylation; Proliferating Cell Nuclear Antigen; Prostate-Specific Antigen; Prostatic Neoplasms; Protein Tyrosine Phosphatases; Transfection; Tumor Cells, Cultured; Xenograft Model Antitumor Assays

Androgens and mesenchymal factors are essential extracellular signals for the development as well as the functional activity of the prostate epithelium. Little is known of the intraepithelial determinants that are involved in prostatic differentiation. Here we found that hepatocyte nuclear factor-3 alpha (HNF-3 alpha), an endoderm developmental factor, is essential for androgen receptor (AR)-mediated prostatic gene activation. Two HNF-3 cis-regulatory elements were identified in the rat probasin (PB) gene promoter, each immediately adjacent to an androgen response element. Remarkably, similar organization of HNF-3 and AR binding sites was observed in the prostate-specific antigen (PSA) gene core enhancer, suggesting a common functional mechanism. Mutations that disrupt these HNF-3 motifs significantly abolished the maximal androgen induction of PB and PSA activities. Overexpressing a mutant HNF-3 alpha deleted in the C-terminal region inhibited the androgen-induced promoter activity in LNCaP cells where endogenous HNF-3 alpha is expressed. Chromatin immunoprecipitation revealed in vivo that the occupancy of HNF-3 alpha on PSA enhancer can occur in an androgen-depleted condition, and before the recruitment of ligand-bound AR. A physical interaction of HNF-3 alpha and AR was detected through immunoprecipitation and confirmed by glutathione-S-transferase pull-down. This interaction is directly mediated through the DNA-binding domain/hinge region of AR and the forkhead domain of HNF-3 alpha. In addition, strong HNF-3 alpha expression, but not HNF-3 beta or HNF-3 gamma, is detected in both human and mouse prostatic epithelial cells where markers (PSA and PB) of differentiation are expressed. Taken together, these data support a model in which regulatory cues from the cell lineage and the extracellular environment coordinately establish the prostatic differentiated response.

Topics: Acid Phosphatase; Androgen-Binding Protein; Animals; Base Sequence; Binding Sites; DNA-Binding Proteins; Enhancer Elements, Genetic; Epithelial Cells; Gene Expression Regulation; Hepatocyte Nuclear Factor 3-alpha; Humans; Male; Mice; Mice, Inbred Strains; Molecular Sequence Data; Mutation; Nuclear Proteins; Promoter Regions, Genetic; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Protein Structure, Tertiary; Protein Tyrosine Phosphatases; Rats; Receptors, Androgen; Regulatory Sequences, Nucleic Acid; Transcription Factors; Transcriptional Activation; Tumor Cells, Cultured

Human prostate cancer PC3 cells were treated in vitro with psychosomatic power emitted by a Buddhist-Zen Master. A significant decrease of growth rate was observed as determined by MTT assay after 48 hours. These cells also had two- to three-fold higher levels of prostatic acid phosphatase (PAcP) activity, a prostate tissue-specific differentiation antigen. In addition, the treated cells formed fewer and smaller colonies in soft agar as compared with control cells, which displayed anchorage-independent growth. These observations provide insight into the suppressive effects of healing power through the practice of Buddhist-Zen meditation on tumor progression. The emitted bioenergy may be suggested as an alternative and feasible approach for cancer research and patient treatment.

Topics: Acid Phosphatase; Buddhism; Humans; In Vitro Techniques; Male; Meditation; Prostatic Neoplasms; Protein Tyrosine Phosphatases; Psychophysiology; Psychosomatic Medicine; Time Factors; Treatment Outcome; Tumor Cells, Cultured

To find out Gleason grades, scores and to see the correlation of these morphological features with tumour markers in prostatic carcinoma.. A descriptive study.. The study was conducted at the Departments of Histopathology and Chemical Pathology, Armed Forces Institute of Pathology, Rawalpindi, over a period of one year.. Fifty cases of prostatic carcinoma were studied. Gleason grades and score of tumour were determined by doing haematoxylin and eosin (HE) staining. Pre-operative serum prostatic acid phosphatase (PAP) and prostate-specific antigen (PSA) assays were carried out in these cases.. The patients seen were between 50-102 years of age with an average of 70.9 years. There were 49 cases of adenocarcinoma and 01 case of mixed adeno and transitional cell carcinoma of prostate. Twenty-eight (56%) patients had Gleason score of 5-7. Twenty-nine (58%) patients were having serum PSA levels between 10.0 ng/ml and 50.0 ng/ml. Thirteen (26%) cases showed PSA assays >50 ng/ml. The sensitivity of PSA test was 84 % in these cases. Thirty-five (70%) patients were having PAP values >3.7 U/l (sensitivity 70 %).. The Gleason grading system is a specific morphological predictor. The serum PSA showed better sensitivity and specificity with Gleason grades and scores as compared to serum PAP. The serum PAP levels showed better correlation with morphological features as compared to serum PSA.

Topics: Acid Phosphatase; Adenocarcinoma; Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoma, Transitional Cell; Humans; Male; Middle Aged; Predictive Value of Tests; Prostate-Specific Antigen; Prostatic Neoplasms; Protein Tyrosine Phosphatases

To examine the utility and prognostic significance of enzymatic serum acid phosphatase (total acid phosphatase, TAP, and prostatic fraction of acid phosphatase, PFAP) and alkaline phosphatase (ALP) for staging, grading and outcome of patients who underwent radical retropubic prostatectomy (RRP) after the introduction of prostate-specific antigen (PSA) testing.. In all, 180 consecutive patients with clinically localized prostate cancer who underwent RRP with standard obturator lymph-node dissection between 1 January 1990 and 31 December 1995 were evaluated. Levels of TAP of > 5.4 IU/L, PFAP of > 1.2 IU/L and ALP of > 120 IU/L were classified as abnormally high. The relationship between abnormally high values and prostate cancer stage, grade and time to recurrence after RRP were calculated. The median follow-up was 86 months (approximately 7 years).. Of the 180 patients, information about preoperative TAP, PFAP and ALP were available in 164, 163 and 154, respectively; TAP was abnormal in seven (4%), PFAP in 33 (20%) and ALP in only 13 (8%). None of the markers examined was associated with any variables of disease severity, as measured by pathological stage, Gleason score, perineural invasion, capsular penetration, positive margins, seminal vesicle involvement, and lymph node involvement. Abnormal TAP, PFAP or ALP were not associated with recurrence (P = 0.96, 0.45 and 0.41, respectively). In contrast, a PSA level of > 4 ng/mL was predictive of recurrence after RRP (P < 0.001). In the sample overall, 25 (14%) of the patients had recurrence and only one died from prostate cancer.. Preoperative enzymatic serum TAP, PFAP and ALP levels are not predictors of the severity of disease or PSA disease-free recurrence after RRP.

Topics: Acid Phosphatase; Aged; Alkaline Phosphatase; Biopsy; Disease-Free Survival; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Postoperative Care; Prostate-Specific Antigen; Prostatectomy; Prostatic Neoplasms; Retrospective Studies

Prostatic epithelial polyps, also known as adenomatous polyps or papillary adenomas with prostatic type epithelium, are uncommon lesions. These lesions typically involve the adult male urethra, trigone, or bladder dome. Diagnosis is usually made by biopsy. Presence of clusters of benign columnar cells in urine cytologic material can suggest the presence of such polyps and must be included in the differential diagnosis.

Topics: Acid Phosphatase; Adenomatous Polyps; Adult; Biomarkers, Tumor; Cytodiagnosis; Humans; Immunohistochemistry; Male; Prostate-Specific Antigen; Prostatic Neoplasms; Protein Tyrosine Phosphatases; Therapeutic Irrigation; Urine

This was a ten-year, hospital-based retrospective study for the incidence and clinical pattern of prostate cancer in southeastern Nigeria. Clinical information extracted from the files included the TNM stage, histo-pathological grading, level of prostatic acid phosphatase (PAP), mode of presentation and clinical and biochemical response to intravenous and oral diethylstilboestrol diphosphate (Honvan)/ orchidectomy. There were 145 patients, mean age 66.6 + 9.8 years, giving an incidence of 61.3 per 10(5), with 54% under 70 years. Most patients (81.4%) presented late, with 62% metastatic. Over 98% were adenocarcinomas, 77% of which were moderate to well-differentiated cancers. PAP was elevated in 109 patients (75%), (representing 92% of all advanced tumours), and normal in 36 (25%). Forty-two percent of poorly differentiated cancers had normal levels of PAP. Most patients presented with urinary retention (56%), prostatism (44%), anaemia (41%), recurrent UTI (35%), bone pains (20%), haematuria (18%), backache (16%) and paraplegia (6%). Nearly 79% responded to treatment with lowered PAP levels and improved quality of life, within a mean of 26.3+/-13.8 months (range 5-78); objective 81 (58%), subjective 32 (23%), no response 27 (19%). Among paraplegics, 78% had full, and 22% had partial motor recovery. Patients with poorly differentiated cancers had only a 33% two-year survival rate. This study confirmed an upward, though moderate trend in the incidence of prostate cancer in Nigeria. The use of PAP instead of PSA as the tumor marker, a local diet with high fish content but lower animal fat, and poor hospital access may account for the lower incidence in the southeast. Poor health education may account for the high rate of late presentations.

Topics: Acid Phosphatase; Adenocarcinoma; Age Distribution; Aged; Humans; Incidence; Male; Middle Aged; Neoplasm Staging; Nigeria; Prostatic Neoplasms; Protein Tyrosine Phosphatases; Retrospective Studies

Prostatic adenocarcinoma and urothelial carcinoma (transitional cell carcinoma) may coexist in the prostate. However, a carcinoma with mixed features has not been recognized. Four cases, three surgical pathology cases and one autopsy case of prostatic adenocarcinoma with urothelial carcinoma features, were retrospectively found in a urological pathology teaching file maintained from 1984 to 1993. Subsequently, 181 consecutive cases of radical prostatectomy from 1994 to 1999 were reviewed, and two prostatic adenocarcinoma areas with features of urothelial carcinoma were identified. Areas with urothelial carcinoma features were identified in the intraductal component of the carcinoma in five cases and in the invasive component in three cases. The intraductal carcinoma with urothelial carcinoma areas usually merged with regions of prostatic adenocarcinoma with a papillary or cribriform pattern. All prostatic adenocarcinomas having areas with urothelial carcinoma features were of high stage, and five of six cases had ductal features. The urothelial carcinoma component displayed a positive reactivity for thrombomodulin and negative or weaker reactivity for PAP and PSA than the prostatic adenocarcinoma component in the same tumor. Excluding the case noted at autopsy, all patients died of the disease within 3 years. Urothelial carcinoma features were usually associated with ductal carcinoma of high stage. Areas of prostatic adenocarcinoma with urothelial carcinoma features should be considered histopathologically as areas of mixed carcinoma of the prostate. Prostatic adenocarcinoma with areas of urothelial carcinoma features may pose a difficult differential diagnosis problem with urothelial carcinoma, especially with small biopsies with focal weak immunoreactivity for PAP, PSA, and thrombomodulin.

Topics: Acid Phosphatase; Adenocarcinoma; Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoembryonic Antigen; Carcinoma, Transitional Cell; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Male; Middle Aged; Prostate-Specific Antigen; Prostatic Neoplasms; Protein Tyrosine Phosphatases; Thrombomodulin

Induction of apoptosis and androgen ablation are two major approaches for treating human prostate carcinoma. In a study of the bioactive components of the soft coral Nephthea chabroli, we found that lemnabourside is a 5alpha-reductase inhibitor, as shown by its ability to inhibit the conversion of testosterone into the more potent dihydrotestosterone in rat prostate homogenate. The compound also inhibited the incorporation of tritiated thymidine into human prostate androgen-dependent carcinoma LNCaP cells, and thus blocking the cell proliferation (IC50 = 37.5 microM). The expression of prostate marker genes, including 5alpha-reductase, prostate-specific antigen, prostatic acid phosphatase and androgen receptor, and the anti-apoptotic bcl-2 gene were markedly reduced, but the transcription of apoptosis-related caspase 3 gene showed a dose-dependent increase in lemnabourside-treated LNCaP cells. Immunofluorescent microscopy and flow cytometric analysis further demonstrated apoptotic changes in these cells. Taken all results together, a relatively weak 5alpha-reductase inhibitory activity on LNCaP cells (EC50 > 250 microM), and a similar growth inhibitory activity on both androgen dependent- and independent-prostate cells (IC50 approximately 37.5 microM) indicated that caspase-3 apoptosis pathway is one of the possible antiproliferative activities mediated by lemnabourside.

Topics: 3-Oxo-5-alpha-Steroid 4-Dehydrogenase; Acid Phosphatase; Adenocarcinoma; Animals; Antineoplastic Agents; Apoptosis; Caspase 3; Caspases; Cell Division; Diterpenes; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Glycosides; Humans; Male; Prostate-Specific Antigen; Prostatic Neoplasms; Proto-Oncogene Proteins c-bcl-2; Receptors, Androgen; Tumor Cells, Cultured

This study provides detailed staining results for 225 prostate adenocarcinomas, including 150 Gleason score 8, 9, and 10 adenocarcinomas with cytokeratins (CKs) 7, 20, 5/6, and 17, prostate-specific antigen (PSA), prostatic acid phosphatase (PAP), carcinoembryonic antigen (CEA), WT1, thyroid transcription factor-1 (TTF-1), and villin. CK7 was reactive in 112 adenocarcinomas (49.8%). The percentage of CK7-reactive adenocarcinomas and the percentage of CK7-stained cells increased in higher Gleason score adenocarcinomas; most reactive neoplasms had CK7 staining of fewer than 25% of cells. CK20 had similar results. The percentage of PSA- and PAP-reactive adenocarcinomas and the percentage of stained cells in reactive neoplasms decreased in higher Gleason score adenocarcinomas. CK5/6 and CK17, WT1, CA-125, TTF-1, and villin were nonreactive. The prostate can be the primary site of metastatic adenocarcinoma that is nonreactive for PAP and PSA and has CK7 or CK20 reactivity in fewer than 50% of the cells. The likelihood that a metastatic adenocarcinoma is from the prostate is low if reactivity with any of the cytokeratin antibodies, CEA, TTF-1, CA-125, WT1, or villin is extensive.

Topics: Acid Phosphatase; Adenocarcinoma; CA-125 Antigen; Carcinoembryonic Antigen; Carrier Proteins; Humans; Immunophenotyping; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Male; Microfilament Proteins; Nuclear Proteins; Prostate-Specific Antigen; Prostatic Neoplasms; Thyroid Nuclear Factor 1; Transcription Factors; WT1 Proteins

Topics: Acid Phosphatase; Alkaline Phosphatase; Androgens; Castration; Estrogens; History, 20th Century; Humans; Male; Prostatic Neoplasms

We undertook a detailed histologic study to identify specific morphologic features that may aid in distinguishing prostatic adenocarcinoma with lung metastases (PALM) from other pulmonary tumors with similar histologic features. In 16 cases, we found 3 predominant architectural patterns: microacinar (n = 10), tubulopapillary (ductal; n = 4), and carcinoid-like (n = 2). Characteristic features of PALM included small acinar and/or cribriform growth, frequent lymphangitic permeation, lack of stromal response, uniform round nuclei with prominent nucleoli, intraluminal blue mucin, and prominent cell borders. By immunohistochemical staining, prostate-specific antigen and prostate-specific acid phosphatase were present in 13 of 14 and 13 of 13 cases, respectively. Metastatic prostatic duct adenocarcinoma exhibited morphologic features similar to metastatic colonic adenocarcinoma. Two cases had a carcinoid-like appearance with nested or solid architecture, parachromatin clearing, and prominent nucleoli, but lacked the finely stippled chromatin pattern of carcinoid tumors. Several features that may result in misinterpretation or lack of association of the neoplasm in the lung with a prostatic primary include lung metastasis preceding the detection of a prostatic primary tumor, solitary pulmonary nodule, tubulopapillary (ductal) or carcinoid-like pattern, scant material in which histologic features of metastatic prostate carcinoma are not fully appreciated, and frequent necrosis. Attention to specific discriminating histologic features, supported by immunohistochemical staining, may be useful in the differential diagnosis, which is therapeutically and prognostically critical.

Topics: Acid Phosphatase; Adenocarcinoma; Cell Nucleolus; Cell Nucleus; Diagnosis, Differential; Humans; Immunohistochemistry; Lung Neoplasms; Male; Mucins; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms

The level of prostatic acid phosphatase in serum is an established marker for prostate carcinoma.. Inactivation of homogeneous prostatic acid phosphatase from human seminal fluid by purified plasmin and human serum was studied in the presence and absence of bovine pancreatic trypsin inhibitor, a plasmin inhibitor, or phenylmethylsulfonylfluoride, a serine protease inhibitor.. Plasmin or serine protease inhibitors protect against prostatic acid phosphatase inactivation in serum samples.. The immediate addition of serine protease inhibitors to serum samples taken for prostatic acid phosphatase determinations should provide more accurate results and permit extended storage of samples. The stabilization of the enzyme activity and immunological properties of prostatic acid phosphatase in blood samples by these protease inhibitors resurrects the clinical significance of prostatic acid phosphatase measurements in prostate cancer screenings.

Topics: Acid Phosphatase; Antifibrinolytic Agents; Biomarkers; Enzyme Stability; Humans; Male; Mass Screening; Organ Specificity; Prostate; Prostatic Neoplasms; Protease Inhibitors; Protein Denaturation; Protein Tyrosine Phosphatases; Specimen Handling; Time Factors

Topics: Acid Phosphatase; Animals; Biomarkers, Tumor; Bone Neoplasms; Combined Modality Therapy; Diethylstilbestrol; Dogs; Estradiol; Estradiol Congeners; Follow-Up Studies; History, 20th Century; Humans; Male; Orchiectomy; Prognosis; Prostatic Neoplasms; Protein Tyrosine Phosphatases; Reference Values; Testosterone

The cellular form of human prostatic acid phosphatase (PAcP) is a neutral protein-tyrosine phosphatase (PTP) and may play a key role in regulating the growth and androgen responsiveness of prostate cancer cells. The functional role of the enzyme is at least due in part to its dephosphorylation of c-ErbB-2, an in vivo substrate of the enzyme. In this study, we investigated the molecular mechanism of phosphotyrosine dephosphorylation by cellular PAcP. We mutated several amino acid residues including one cysteine residue that was proposed to be involved in the PTP activity of the enzyme by serving as the phosphate acceptor. The cDNA constructs of mutant enzymes were transiently transfected into C-81 LNCaP and PC-3 human prostate cancer cells that lack the endogenous PAcP expression. The phosphotyrosine level of ErbB-2 in these transfected cells was subsequently analyzed. Our results demonstrated that the phosphotyrosine level of ErbB-2 in cells expressing H12A or D258A mutant PAcP is similar to that in control cells without PAcP expression, suggesting that these mutants are incapable of dephosphorylating ErbB-2. In contrast, cells expressing C183A, C281A, or wild-type PAcP had a decreased phosphotyrosine level of ErbB-2, compared with the control cells. Similar results were obtained from in vitro dephosphorylation of immunoprecipitated ErbB-2 by these mutant enzymes. Furthermore, transient expression of C183A, C281A, or the wild-type enzyme, but not H12A or D258A, decreased the growth rate of C-81 LNCaP cells. The data collectively indicate that His-12 and Asp-258, but not Cys-183 or Cys-281, are required for the PTP activity of PAcP.

Topics: Acid Phosphatase; Catalytic Domain; DNA Mutational Analysis; Humans; Male; Mitogen-Activated Protein Kinases; Mutagenesis, Site-Directed; Neoplasm Proteins; Phosphorylation; Prostatic Neoplasms; Protein Tyrosine Phosphatases; Receptor, ErbB-2

Steroid hormones can have profound effects on prostate tumor development making it important to define steroid receptor expression in prostate tissues. For this purpose, androgen receptor (AR) and estrogen receptor (ER alpha and ER beta) expression was quantified in 12 clinically localized and 11 hormone-refractory sporadic prostate tumors, using real-time quantitative reverse transcription-PCR assays. To gain more insight into hormone-responsiveness, estrogen-regulated progesterone receptor (PGR) and androgen-regulated prostatic acid phosphatase (PAP) mRNA levels were also quantified. There is a decrease in expression of ER beta in both clinically localized and hormone-refractory tumors relative to normal prostate tissues. Moreover, hormone-refractory tumors display a decreased expression of ER alpha and an increased expression of AR. There is a positive association between ER alpha, ER beta, and PGR expression (P < 0.0001) and a negative association between AR and the androgen-regulated gene PAP expression in hormone-refractory tumors. Taken together, these data indicate that, although increased expression of the AR gene might play a key role in endocrine treatment failure, it cannot be considered as the sole actor of this unresolved dilemma, and abnormalities in ER alpha and/or ER beta expression may also modulate the growth response of prostate cancer to hormone withdrawal. Our results also suggest that ER alpha and ER beta expression status could be used to identify advanced prostate tumor patients who may respond to antiestrogen therapy.

Topics: Acid Phosphatase; Estrogen Receptor alpha; Estrogen Receptor beta; Gene Expression; Gene Expression Regulation, Neoplastic; Humans; Male; Prostate; Prostatic Neoplasms; Receptors, Androgen; Receptors, Estrogen; Receptors, Progesterone; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger

Protein patterns in cells collected from benign prostatic tissues and prostate carcinomas were analyzed using two-dimensional polyacrylamide gel electrophoresis and mass spectrometry. Polypeptide expression was evaluated by computer-assisted image analysis (PDQUEST). Proteins expressed by prostate tumors were identified via in-gel digestion and subsequent matrix-assisted laser desorption/ionization mass spectrometry. In addition to cytoskeletal and mitochondrial proteins, a 40-kDa protein was identified as prostatic acid phosphatase (PAP). PAP expression decreased approximately twofold between benign and malignant tissue. Increased expression of heat shock protein 70 and decreased expression of tropomyosin 1 were also observed in the malignant tissue. The analysis of prostate material by two-dimensional gel electrophoresis and mass spectrometry shows that particular proteins are of interest as markers of disease.

Topics: Acid Phosphatase; Adenocarcinoma; Aged; Aged, 80 and over; Drosophila Proteins; Electrophoresis, Gel, Two-Dimensional; HSP70 Heat-Shock Proteins; Humans; Male; Middle Aged; Neoplasm Proteins; Prostatic Hyperplasia; Prostatic Neoplasms; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Tropomyosin

Serum acid phosphatase (ACP) was once used as the marker for advanced prostate cancer. However, with the development of assays for prostate-specific antigen (PSA), a more sensitive and specific tumor marker, the use of ACP has diminished. We investigated the prognostic value of preoperative serum ACP in predicting prognosis for men with localized prostate cancer following radical retropubic prostatectomy (RRP).. Of 2293 men treated from 1982 to 1998, 1681 men had a preoperative ACP measurement using an enzymatic assay. We analyzed the actuarial freedom from biochemical (PSA) progression following RRP according to ACP levels. We used multivariate logistic regression and proportional hazards models to determine the independent prognostic value of ACP level with respect of pathologic stage and biochemical recurrence.. ACP was not an independent predictor of organ confinement or lymph node involvement in the multivariate logistic regression models using preoperative variables. However, in the proportional hazards model, ACP was an independent predictor of tumor recurrence following RRP, and there was a statistically significant improvement in biochemical recurrence-free survival for men with lower levels of ACP (P <0.001). Furthermore, the normalized hazard ratios of ACP and PSA for predicting biochemical recurrence were similar.. Stratification of men according to their preoperative ACP levels was predictive of patient outcome after RRP. Proportional hazards modeling using preoperative variables demonstrated that the serum ACP level is an independent predictor of tumor recurrence following RRP.

Topics: Acid Phosphatase; Actuarial Analysis; Biomarkers, Tumor; Disease-Free Survival; Follow-Up Studies; Humans; Lymphatic Metastasis; Male; Multivariate Analysis; Neoplasm Staging; Prognosis; Proportional Hazards Models; Prostatectomy; Prostatic Neoplasms; Retrospective Studies

In vitro and experimental studies of mesenchymal-epithelial interaction for the prostatic stroma have demonstrated that the prostatic stroma is capable of inducing the nonprostatic epithelium to acquire many features of prostatic epithelium. We investigated whether this phenomenon could be observed in vivo in human prostatic stroma. MATERIALS AND METHODS Sixty transitional cell carcinoma (TCC) of the urinary bladder: (a) 20 with glandular lumen; (b) 20 without glandular lumen: (c) 10 mixed TCC-adenocarcinoma (ACA); and (d) 10 with synchronous or metachronous TCC of the prostate; and three primary TCC of the prostate were examined and submitted for immunostaining for prostatic acid phosphatase (PAP) and prostatic specific antigen (PSA).. There was a spectrum of immunostaining for PSA ranging from negative reactivity in TCC without glandular lumen of the urinary bladder, to focal and weak reactivity in single cells with varying degrees of nonmucinous glandular differentiation and to strong reactivity in groups of cells in primary and synchronous or metachronous TCC in the prostate. The areas of carcinoma geographically closest to the prostate and with the most extensive nonmucinous glandular differentiation displayed the most frequent and strongest immunoreactivity for PSA. The immunoreactivity for PAP was usually stronger than for PSA. Four cases of TCC and mixed TCC-ACA were immunoreactive only for PAP. Furthermore, there was a change in the phenotype of TCC in the urinary bladder as it spread into the prostate. For 10 TCC in the urinary bladder with synchronous or metachronous tumor in the prostate, all TCC in the urinary bladder were negative for PAP and PSA, whereas six TCC in the prostate were focally positive.. The spectrum of immunoreactivity for PAP and PSA and the change in immunoreactivity of TCC of the urinary bladder as it spreads into the prostate are likely induced by the prostatic stroma through the mechanism of mesenchymal-epithelial interaction. Prostate 47:172-182, 2001.

Topics: Acid Phosphatase; Aged; Aged, 80 and over; Carcinoma, Transitional Cell; Cell Differentiation; Female; Humans; Immunohistochemistry; Male; Middle Aged; Phenotype; Prostate-Specific Antigen; Prostatic Neoplasms; Urinary Bladder Neoplasms

Cytotoxic T cells (CTL) are considered one of the primary effector cell populations in antitumor immunity. Recent studies, however, have demonstrated the critical importance of helper T cells (Th), specifically interferon gamma (IFN gamma)-secreting Th1 cells, either by supporting an appropriate CTL environment or by recruiting other effector cells. We evaluated whether patients with prostate cancer have naturally occurring Th-cell responses specific for two prostate cancer-associated antigens, prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP), and whether Th1-type responses to these antigens could be detected.. Peripheral blood mononuclear cells (PBMC) were collected from 80 patients with prostate cancer and 20 male controls without prostate disease. Th-cell responses were evaluated by measuring antigen-specific proliferation. IFN gamma and IL-5 secretion in response to antigen stimulation was determined by enzyme-linked immunosorbent assay.. T cell proliferative responses specific for PSA and PAP could be detected in patients with prostate cancer. Six percent (5/80) of patients had T cell responses specific for PSA and 11% (9/80) for PAP. T cell responses specific for PSA were more prevalent in patients with metastatic disease (P = 0.02), whereas responses specific for PAP could be detected in patients irrespective of disease stage. IFN gamma-producing Th cells, specific for both PSA and PAP, could be identified in patients with prostate cancer.. Patients with prostate cancer can have detectable Th-cell responses specific for the prostate cancer-associated proteins PSA and PAP. The presence of antigen-specific Th1 immune responses in prostate cancer patients suggests that an immune environment capable of supporting antigen-specific CTL may exist in vivo. Prostate 47:222-229, 2001.

Topics: Acid Phosphatase; Enzyme-Linked Immunosorbent Assay; Epitopes, T-Lymphocyte; Humans; Interferon-gamma; Interleukin-5; Lymphocyte Activation; Male; Middle Aged; Neoplasm Metastasis; Neoplasm Staging; Phenotype; Prostate-Specific Antigen; Prostatic Neoplasms; Th1 Cells

Helper T cells (Th cells) play a central role in the initiation and maintenance of immune responses, including antitumor immunity. The ability of Th cells in murine models to maintain and enhance the cytolytic efficacy of CD8+ CTLs has led to a renewed interest in identifying human tumor antigens recognized by Th cells. Prostatic acid phosphatase (PAP) is a prostate cancer-associated tumor antigen. A rodent model has demonstrated that PAP-specific CTLs can induce destructive prostatitis. Human MHC class I epitopes derived from PAP have been identified previously, and peptide-specific CTLs have been shown to be able to lyse an MHC-restricted prostate cancer cell line. In the current study, we sought to identify Th epitopes derived from PAP that might be used to elicit PAP-specific Th responses, ultimately in the context of human vaccines targeting PAP. Using peripheral blood mononuclear cells (PBMCs) from subjects with and without PAP-specific Th responses, we screened a panel of 10 potential peptide epitopes for peptide-specific T-cell proliferation. Four peptides, p81-95, p199-213, p228-242, and p308-322, were identified for which peptide-specific T-cell proliferation occurred in the majority of patient PBMC samples that also exhibited PAP-specific T-cell proliferation. PBMCs from patients with prostate cancer and without PAP-specific Th immunity were then cultured in vitro with these four peptides. Peptide-specific T-cell lines could be generated from two of the four peptides, p199-213 and p228-242, that also proliferated in response to PAP protein stimulation. The ability of these two peptides to elicit PAP-specific Th responses suggests that they represent naturally processed PAP-specific MHC class II epitopes.

Topics: Acid Phosphatase; Amino Acid Sequence; Cancer Vaccines; Epitopes, T-Lymphocyte; Histocompatibility Antigens Class II; Humans; Lymphocyte Activation; Male; Molecular Sequence Data; Peptide Fragments; Prostatic Neoplasms; Protein Tyrosine Phosphatases; T-Lymphocytes, Helper-Inducer

We investigated the clinical usefulness of measuring the serum concentrations of pyridinoline cross-linked carboxyterminal telopeptide of type I collagen (ICTP) and carboxyterminal propeptide of type I procollagen (PICP) as markers for monitoring metastatic bone activity in patients with prostate cancer.. Serum levels of ICTP, PICP, alkaline phosphatase, prostatic acid phosphatase and prostate specific antigen (PSA) were analyzed in 104 untreated patients with prostate cancer, including 62 with and 42 without bone metastasis. Serial measurements of ICTP, PICP and PSA were performed during hormonal therapy in 35 of 62 prostate cancer patients with bone metastasis.. Serum levels of all markers except prostatic acid phosphatase were significantly higher with than without bone metastasis. The median values of each marker increased according to the extent of bone metastasis. Serial ICTP, PICP and PSA in 19 patients with a partial response or no change in bone scans demonstrated a downward trend after treatment, while in 16 with progression they showed an upward trend after treatment. The rate of detecting bone metastasis and progression using ICTP were highest compared with other markers based on the percent clinical effectiveness and receiver operating characteristic curves.. Measuring serum ICTP may be useful for detecting bone metastasis and prostate cancer progression, and may augment PSA and bone scan monitoring of metastatic bone activity.

Topics: Acid Phosphatase; Adenocarcinoma; Aged; Aged, 80 and over; Alkaline Phosphatase; Biomarkers, Tumor; Bone Neoplasms; Collagen; Collagen Type I; Humans; Male; Middle Aged; Peptide Fragments; Peptides; Procollagen; Prostate-Specific Antigen; Prostatic Neoplasms; Protein Tyrosine Phosphatases

Human prostatic acid phosphatase is a prostate specific differentiation antigen. Prostatic acid phosphatase levels increase in the serum of patients with prostate cancer and its peptide from positions 299 to 307 (PAP 299-307) is recognized by HLA-A2 restricted cytotoxic T lymphocytes. We investigated whether HLA-A2402 binding prostatic acid phosphatase derived peptides induce HLA-A2402 restricted, tumor specific cytotoxic T lymphocytes from the peripheral blood mononuclear cells of patients with prostate cancer.. Peptide binding activity was measured with RMA-S-A*A2402 cell lines and flow cytometry. Cytotoxic T-lymphocyte activity of the peripheral blood mononuclear cells of patients with prostate cancer and healthy donors was measured by interferon-gamma and (51)creatinine release assays. Prostatic acid phosphatase expression in the tumor cell lines at the messenger RNA and protein levels was investigated by reverse transcriptase-polymerase chain reaction and immunohistochemical analysis, respectively.. An HLA-A2402 binding, prostatic acid phosphatase derived peptide consisting of the prostatic acid phosphatase amino acid sequence from positions 213 to 221 (PAP 213-221, LYCESVHNF) showed the ability to induce HLA-A2402 restricted and tumor specific cytotoxic T lymphocytes, which are cytoxic to prostatic acid phosphatase positive tumor cells from the peripheral blood mononuclear cells of patients with prostate cancer.. PAP 213-221 may be appropriate as a cancer vaccine for specific immunotherapy in patients with HLA-A2402 positive prostate cancer.

Topics: Acid Phosphatase; HLA-A Antigens; HLA-A24 Antigen; Humans; Male; Peptides; Prostatic Neoplasms; Protein Tyrosine Phosphatases; T-Lymphocytes, Cytotoxic; Tumor Cells, Cultured

We report herein a case of a collision tumor composed of high-grade urothelial carcinoma and a Gleason grade 3+4 prostate adenocarcinoma metastasizing to the same lymph node. After the patient underwent cystoprostatectomy for known urothelial carcinoma, he was incidentally discovered to have a second primary prostate tumor. Lymph node examination revealed that one node appeared to have metastatic foci from both primary tumors. The presence of 2 tumor types colliding in the same lymph node was confirmed using immunohistochemical stains, including monoclonal carcinoembryonic antigen, prostate-specific antigen, prostatic acid phosphatase, cytokeratins 7 and 20, and CD57. We also stained both primary tumors with the same panel as an internal control. Although 2 similar collision tumors have been reported in the literature in the past, neither used a battery of immunohistochemical stains to definitively distinguish one tumor from the other. Herein, we review the literature on urothelial and prostate collision tumors and some of the special stains used to distinguish them.

Topics: Acid Phosphatase; Adenocarcinoma; Aged; Carcinoma, Transitional Cell; CD57 Antigens; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Lymph Nodes; Lymphatic Metastasis; Male; Neoplasms, Second Primary; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Urinary Bladder Neoplasms

Understanding cell proliferation regulation in hormone refractory prostate cancer may provide answers for novel solutions. Protein tyrosine phosphatases have been thought to have key roles in regulating cell proliferation and be involved in oncogenesis, although to our knowledge their functional roles in human prostate cancer remain unknown. Human prostatic acid phosphatase (PAcP), a major phosphatase in prostate epithelium, has been shown to function as a neutral protein tyrosine phosphatase in these cells. We evaluated the biological significance of cellular prostatic acid phosphatase expression in human prostate cancer cells.. Immunohistochemical testing of human prostate cancer archival specimens was done to evaluate the expression of cellular PAcP. Immunoprecipitation and immunoblotting were performed to determine cellular PAcP and SH2 domain-bearing tyrosine phosphatase-1 levels as well as tyrosine phosphorylation of c-ErbB-2/neu in different human prostate cancer cells. The biological behavior of LNCaP derivative sublines was characterized in vitro and in vivo by soft agar analysis and xenograft animal inoculation.. Immunohistochemical staining of human prostate clearly showed that cellular levels of PAcP significantly decreases in prostate cancer cells (p <0.001). The results of biochemical characterization revealed that the cellular level of PAcP but not SHP-1, another differentiation associated protein tyrosine phosphatase, consistently correlated negatively with the growth of several human prostate cancer cell lines. Reintroducing cellular PAcP activity in prostate cancer cells by PAcP complementary DNA transfection resulted in decreased tyrosine phosphorylation of c-ErbB-2/neu, decreased proliferation rates in culture as well as decreased anchorage independent growth in soft agar. The xenograft animal model demonstrated that a higher tumor growth rate as well as larger size is associated with a lower level of cellular PAcP.. Cellular PAcP can down-regulate prostate cancer cell growth, at least partially by dephosphorylating c-ErbB-2/neu. Therefore, decreased cellular PAcP expression in cancer cells may be involved in prostate cancer progression.

Topics: Acid Phosphatase; Androgens; Animals; Blotting, Western; Down-Regulation; Female; Humans; Immunohistochemistry; Male; Mice; Phosphorylation; Prostate; Prostatic Neoplasms; Protein Phosphatase 1; Protein Tyrosine Phosphatases; Receptor, ErbB-2; Transplantation, Heterologous

Topics: Acid Phosphatase; Adenocarcinoma; Bone Neoplasms; Humans; Male; Middle Aged; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Radionuclide Imaging; Radiopharmaceuticals; Technetium Tc 99m Medronate

hK4 (prostase, KLK4), a recently cloned prostate-specific serine protease and a member of the tissue kallikrein family, is a zymogen composed of 228 amino acid residues including an amino-terminal propiece, Ser-Cys-Ser-Gln-. A chimeric form of hK4 (ch-hK4) was constructed in which the propiece of hK4 was replaced by that of prostate-specific antigen (PSA) to create an activation site susceptible to trypsin-type proteases. ch-hK4 was expressed in Escherichia coli, isolated from inclusion bodies, refolded, and purified with an overall yield of 25%. The zymogen was readily self-activated during the refolding process to generate an active form (21 kDa) of hK4 (rhK4). rhK4 cleaved the chromogenic substrates Val-Leu-Arg-pNA (S-2266), Pro-Phe-Arg-pNA (S-2302), Ile-Glu-Gly-Arg-pNA (S-2222), and Val-Leu-Lys-pNA (S-2251), indicating that rhK4 has a trypsin-type substrate specificity. The rhK4 was inhibited by aprotinin (6 kDa), forming an equimolar 27 kDa complex. rhK4 readily activated both the precursor of PSA (pro-PSA) and single chain urokinase-type plasminogen activator (scuPA, pro-uPA). rhK4 also completely degraded prostatic acid phosphatase but failed to cleave serum albumin, another protein purified from human seminal plasma. These results indicate that hK4 may have a role in the physiologic processing of seminal plasma proteins such as pro-PSA, as well as in the pathogenesis of prostate cancer through its activation of pro-uPA.

Topics: Acid Phosphatase; Amino Acid Sequence; Binding Sites; Humans; Hydrogen-Ion Concentration; Kallikreins; Male; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Protein Precursors; Protein Tyrosine Phosphatases; Recombinant Proteins; Seminal Plasma Proteins; Serine Endopeptidases; Substrate Specificity; Urokinase-Type Plasminogen Activator

The TRAMP-C1 (C1) and TRAMP-C2 (C2) cell lines were derived from a prostate tumor that arose in a mouse from the transgenic adenocarcinoma mouse prostate (TRAMP) model. However, their similarity to primary prostate tumors and therefore their usefulness in immunotherapy studies has not been clearly defined. We showed using RT-PCR that these cell lines exhibited a variety of prostate-specific genes expressed by human prostate tumors that may be used as tumor-associated antigens for immunotherapy. Interestingly, several of these genes are also expressed in cell lines that are not prostatic in origin. The prostate cell lines were also shown to grow in an androgen-independent manner, to be capable of expressing MHC class I and to be susceptible to specific lysis by cytotoxic T lymphocytes. Therefore, these cell lines will provide us with the ability to evaluate immune responses to and tolerance of prostate-specific protein peptides in an animal model.

Topics: Acid Phosphatase; Adenocarcinoma; Animals; Antibody Specificity; Antigens, Neoplasm; Carboxypeptidases; Disease Models, Animal; Gene Expression; Genes, Tumor Suppressor; Glutamate Carboxypeptidase II; GPI-Linked Proteins; Homeodomain Proteins; Immunotherapy; In Vitro Techniques; Male; Membrane Glycoproteins; Mice; Mice, Transgenic; Neoplasm Proteins; Prostatic Neoplasms; Prostatic Secretory Proteins; Protein Tyrosine Phosphatases; Reverse Transcriptase Polymerase Chain Reaction; Transcription Factors; Tumor Cells, Cultured

To determine the value of serum chromogranin A (CgA), a marker of neuroendocrine differentiation, for monitoring prostate cancer: CgA levels were related to three other tumour markers, i.e. total prostate-specific antigen (tPSA), prostatic acid phosphatase (PAP), neurone-specific enolase (NSE), and to testosterone, to assess the importance of hormone withdrawal.. Serum samples (218) were obtained from 118 patients with prostate cancer, including 111 patients with advanced prostate cancer: 103 presented to our centre for systemic radionuclide therapy of painful skeletal metastases. CgA concentrations were measured using a new immunoradiometric assay (IRMA: Cis Bio International, Gif sur Yvette, France) and a threshold of 70 ng/mL was determined after receiver operating characteristic curve analysis. Testosterone was also measured with an IRMA assay; tPSA, PAP and NSE were assayed using the time-resolved amplified cryptate emission.. Serum marker levels were high in 64% of the patients for CgA, 24% for NSE, 89% for tPSA and 81% for PAP. Patients resistant to endocrine treatments and with elevated tPSA (i.e. hormone-independent) showed increased CgA and NSE in 62% and 29%, respectively. Patients with hormone-dependent prostate cancer (i.e. with a normal tPSA level) had elevated CgA in 59% but no abnormal NSE. All patients of the latter group except one showed clinical progression of their disease. However, the mean (SD) concentrations of CgA in hormone-independent (146) or hormone-dependent (22) patients, at 185.3 (449.1) and 160.9 (293.9) ng/mL, respectively, were not statistically different (P=0.8, Mann-Whitney U-test). For 30 patients, blood samples were drawn and markers measured before and after systemic radionuclide therapy. There was a significant increase in the CgA and tPSA concentrations after treatment (P=0.0146 and 0.0025, respectively).. In association with tPSA, serum CgA appears to be a promising marker for monitoring patients with prostate cancer.

Topics: Acid Phosphatase; Antineoplastic Agents, Hormonal; Chromogranin A; Chromogranins; Drug Resistance, Neoplasm; Humans; Male; Phosphopyruvate Hydratase; Prostate-Specific Antigen; Prostatic Neoplasms; Protein Tyrosine Phosphatases; ROC Curve; Sensitivity and Specificity; Testosterone

The stimulated secretion of prostatic acid phosphatase (PAcP) has been known to be a hallmark of androgen action on human prostate epithelial cells for the last five decades. The molecular mechanism of androgen action on PAcP secretion, however, has remained mostly unknown. We investigated the molecular mechanism that promotes PAcP secretion in LNCaP human prostate carcinoma cells which express PAcP and are androgen-responsive. Treatment with 12-o-tetradecanoyl phorbol-13-acetate (TPA), a protein kinase C (PKC) activator, resulted in an increased secretion of PAcP in a dose- and time-dependent fashion. 4Alpha-phorbol, a biologically inactive isomer of TPA, had no effect. This TPA stimulation of PAcP secretion was observed 2 h after exposure, while TPA did not have a significant effect on the mRNA level even with a 6 h treatment. A23187 calcium ionophore, known to mobilize cellular calcium which is a co-factor of PKC, also activated PAcP secretion. This TPA stimulation of PAcP secretion was more potent than the conventional stimulating agent 5alpha-dihydrotestosterone (DHT) at the same concentration of 50 nM. Furthermore, the action of TPA and DHT on PAcP secretion was blocked by five different PKC inhibitors. Results also showed that DHT, as well as TPA, could rapidly modulate PKC activity. Therefore, PKC can regulate PAcP secretion, and may also be involved in DHT action on PAcP secretion.

Topics: Acid Phosphatase; Dihydrotestosterone; Humans; Male; Prostatic Neoplasms; Protein Kinase C; Protein Tyrosine Phosphatases; Signal Transduction; Tetradecanoylphorbol Acetate; Tumor Cells, Cultured

Topics: Acid Phosphatase; Aged; Carcinoma, Endometrioid; Humans; Male; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Scalp; Skin Neoplasms

Recent changes in tissue fixation strategy, using glutaraldehyde, have clarified the secretory mechanisms of the normal prostate identifying cytoplasmic prostatic secretory granules, structures not preserved by formalin fixation. This normal secretory mechanism was absent in most adenocarcinomas, depicting an important metabolic change in transformed prostate cells. The current study further investigates differences between benign and malignant prostate secretion and relates them to the production of corpora amylacea by benign glands and crystalloids or mucin by cancer. In all normal prostate cells examined (6 cases), prostate secretory granules (PSG) were approximately 1-microm, brightly eosinophilic granules filling the cytoplasm of secretory cells and released in packets by a specialized apocrine cell structure. After apocrine decapitation and luminal dispersal, some of the cytoplasmic and PSG remnants condensed to form eosinophilic bodies (EB) with a glycoprotein rim and central protein core. EB were observed adsorbing and layering onto the surface of prostatic corpora amylacea representing their chief mode of enlargement. Biochemical analysis and x-ray diffraction studies confirmed sulfated glycosaminoglycans of similar structure as the main constituent of both PSG and corpora amylacea. Peripheral zone amphiphilic "dark cell" carcinoma (9 cases) contained almost no PSG, and showed neither apical decapitation nor EB formation, but mucin secretion was frequently detected. Crystalloids that share the same staining characteristics and sulfur content as PSG and corpora amylacea were identified in 3 selected "clear cell" carcinomas, all of which showed at least focal PSG secretion. The recognition of these differing secretory mechanisms and their deviation from normal further defines the histological criteria and spectrum of prostate malignancy.

Topics: Acid Phosphatase; Carcinoma; Cytoplasm; Cytoplasmic Granules; Humans; Inclusion Bodies; Male; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms

The current study assesses artificial intelligence methods to identify prostate carcinoma patients at low risk for lymph node spread. If patients can be assigned accurately to a low risk group, unnecessary lymph node dissections can be avoided, thereby reducing morbidity and costs.. A rule-derivation technology for simple decision-tree analysis was trained and validated using patient data from a large database (4,133 patients) to derive low risk cutoff values for Gleason sum and prostate specific antigen (PSA) level. An empiric analysis was used to derive a low risk cutoff value for clinical TNM stage. These cutoff values then were applied to 2 additional, smaller databases (227 and 330 patients, respectively) from separate institutions.. The decision-tree protocol derived cutoff values of < or = 6 for Gleason sum and < or = 10.6 ng/mL for PSA. The empiric analysis yielded a clinical TNM stage low risk cutoff value of < or = T2a. When these cutoff values were applied to the larger database, 44% of patients were classified as being at low risk for lymph node metastases (0.8% false-negative rate). When the same cutoff values were applied to the smaller databases, between 11 and 43% of patients were classified as low risk with a false-negative rate of between 0.0 and 0.7%.. The results of the current study indicate that a population of prostate carcinoma patients at low risk for lymph node metastases can be identified accurately using a simple decision algorithm that considers preoperative PSA, Gleason sum, and clinical TNM stage. The risk of lymph node metastases in these patients is < or = 1%; therefore, pelvic lymph node dissection may be avoided safely. The implications of these findings in surgical and nonsurgical treatment are significant.

Topics: Acid Phosphatase; Algorithms; Artificial Intelligence; Biopsy, Needle; Carcinoma; Cost Control; Databases as Topic; Decision Support Techniques; Decision Trees; False Negative Reactions; Humans; Lymph Node Excision; Lymphatic Metastasis; Male; Neoplasm Staging; Prostate-Specific Antigen; Prostatic Neoplasms; Reproducibility of Results; Risk Factors

Urethral adenomatous polyps with prostatic epithelium (also known as benign prostatic epithelial polyps [BPEPs]) are a documented cause of hematuria, dysuria, and hematospermia, conditions that may prompt cytologic evaluation of urine.. The urine cytologic test findings in 5 cases of biopsy-proven BPEPs and in 1 case of prostatic ductal adenocarcinoma (PDA) that presented as a urethral polyp were retrospectively evaluated. Immunocytochemical stain for prostate-specific antigen (PSA), prostatic acid phosphatase (PAP), and high-molecular-weight cytokeratin (34betaE12) were used in evaluation of the lesions.. In 4 of 5 cases of BPEPs, clusters of bland columnar cells with uniform, oval nuclei were seen. Positive immunostaining for PSA and PAP confirmed the prostatic origin of the clusters in 2 cases. One urine sample contained abundant goblet cells and extracellular mucin, consistent with intestinal metaplasia coexisting in the bladder biopsy specimen. The urine sample in the fifth case of BPEPs contained no columnar cells. The last case had multiple urine cytologic evaluations that demonstrated PSA-positive, malignant-appearing clusters of columnar cells. A biopsy specimen of the polyps was described as a high-grade prostatic intraepithelial neoplasm in adenomatous polyp. However, in this patient, PDA was diagnosed on transurethral resection of the prostate specimen 4 years after the initial urine cytologic test.. Benign prostatic epithelial polyps should be considered in the differential diagnosis of clusters of columnar cells in urine cytologic testing. Cells with malignant nuclear features should instigate a careful search for a (prostatic) neoplasm, which may present as urethral polyps (e.g., PDA). Stains for PSA or PAP are useful adjuncts in differential diagnosis of this condition.

Topics: Acid Phosphatase; Adenocarcinoma; Adenomatous Polyps; Adult; Aged; Diagnosis, Differential; Humans; Keratins; Male; Middle Aged; Prostate-Specific Antigen; Prostatic Neoplasms; Urethral Neoplasms; Urine

Enlargement of the male breast is frequently encountered in the course of adjuvant antiandrogen therapy for advanced prostate carcinoma. The clinical differential diagnosis in this setting includes hormonal imbalance-induced gynecomastia, primary breast carcinoma, and metastasis of prostatic carcinoma. Biopsy of the lesion with the identification of prostate-specific antigen (PSA) plays an important role in establishing the correct diagnosis. Recent studies showed that female mammary epithelium may be a significant source of PSA, but its expression in male breasts has not been sufficiently studied. We found that normal and hyperplastic duct epithelium in gynecomastia exhibited focal, strong (+3) PSA immunoreactivity in 5 of 18 cases (28%). In contrast, no PSA reactivity was found in eight cases of male breast carcinoma. No reactivity was seen with antiprostatic acid phosphatase (PsAP) antibody, in either benign or malignant epithelium. Frequent expression of PSA in gynecomastia may, in an appropriate clinical setting, cause confusion with metastatic prostatic carcinoma. The lack of immunoreactivity for PsAP in male breast epithelium indicates its usefulness in the differential diagnosis.

Topics: Acid Phosphatase; Adolescent; Adult; Aged; Androgen Antagonists; Breast; Breast Neoplasms, Male; Diagnosis, Differential; Epithelium; Female; Gynecomastia; Humans; Immunohistochemistry; Male; Middle Aged; Prostate-Specific Antigen; Prostatic Neoplasms

Receptor protein tyrosine phosphatase alpha (RPTPalpha) is a transmembrane protein phosphatase, and has been proposed to be involved in the differentiation of the neuronal system. In the present study, we demonstrated the expression of RPTPalpha mRNA in several normal human tissues. We further investigated the regulation of expression of RPTPalpha mRNA in epithelial cells utilizing three commercially available human prostate cancer cell lines LNCaP, PC-3 and DU145. This is because these cells exhibit different levels of differentiation, defined by the expression of a tissue-specific differentiation antigen, prostatic acid phosphatase (PAcP), and their androgen sensitivity. LNCaP cells express PAcP and are androgen-sensitive cells, while PC-3 and DU145 cells do not express PAcP and are androgen-insensitive cells. Northern blot analyses revealed that, in LNCaP cells, fetal bovine serum (FBS) and 5alpha-dihydrotestosterone (DHT) down-regulates RPTPalpha mRNA expression, similar to the effect on PAcP. Contrarily, FBS up-regulated the RPTPalpha mRNA level in PC-3 and DU145 cells. In LNCaP cells, sodium butyrate inhibited cell growth and up-regulated RPTPalpha as well as PAcP mRNA expression. Although, sodium butyrate also inhibited the growth of PC-3 and DU145 cells, the level of RPTPalpha mRNA was decreased in PC-3, while increased in DU145 cells. Thus, data taken together indicate that the expression of RPTPalpha is apparently regulated by a similar mechanism to that of PAcP in LNCaP cells.

Topics: Acid Phosphatase; Animals; Blotting, Northern; Butyrates; Carcinogens; Cattle; Dihydrotestosterone; Fetal Proteins; Gene Expression Regulation, Neoplastic; Humans; Male; Prostatic Neoplasms; Protein Tyrosine Phosphatases; Receptor-Like Protein Tyrosine Phosphatases, Class 4; Receptors, Cell Surface; RNA, Messenger; Serum Albumin, Bovine; Tetradecanoylphorbol Acetate; Tumor Cells, Cultured

Fine-needle aspiration of prostatic carcinoma usually yields an acinar carcinoma that is immunoreactive for prostatic-specific antigen (PSA) and prostatic acid phosphatase (PAP). We report on two FNAs of metastatic sarcomatoid prostatic carcinoma that were PSA- and PAP-negative. Our methods included a review of the medical records and pathology results. Both cases presented with elevated serum PSA levels and prostate needle biopsies with Gleason score 8 and 9 tumors, respectively. Both cases developed retroperitoneal/pelvic lymphadenopathy, and fine-needle aspirations were performed. These showed high-grade, sarcomatoid tumors with marked anisonucleosis. Immunocytochemical staining for PSA and PAP was negative in both cases. Clinical and radiologic evaluation failed to reveal any other potential primary sites. Metastatic, sarcomatoid, PSA- and PAP-negative prostatic carcinoma is a rare diagnosis of exclusion that should be considered in the characteristic clinical setting.

Topics: Acid Phosphatase; Adenocarcinoma; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Biopsy, Needle; Carcinoembryonic Antigen; Flutamide; Humans; Immunohistochemistry; Keratins; Leuprolide; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Prostate-Specific Antigen; Prostatic Neoplasms; Sarcoma

We propose that carcinoembryonic antigen (CEA) may be a tumor marker for prostatic cancer in addition to prostate specific antigen (PSA), gamma-seminoprotein and prostate acid phosphatase (PAP). The tests were done on 15 sera and autopsy specimens of prostatic cancer. Eight of them were clinical cancers and the remaining seven were incidental ones. We measured serum PAP, PSA, CEA and CA 19-9 and immunohistochemically evaluated these specimens. In clinical cancers, serum PAP, PSA, CEA and CA 19-9 were 1272.9 +/- 3094.4, 146.7 +/- 233.6, 36.3 +/- 36.0 and 80.4 +/- 92.0. Immunohistochemically, all were positive for PAP, PSA, CEA and CA 19-9. In incidental cancers, serum PAP, PSA, CEA and CA 19-9 were 2.4 +/- 1.5, 7.9 +/- 16.9, 128.1 +/- 182.7 and 201.8 +/- 416.1. We conclude that the patients with higher levels of plasma PAP or PSA should go through CEA and CA 19-9 measurement in order to diagnose clinical prostatic cancer.

Topics: Acid Phosphatase; Autopsy; Biomarkers, Tumor; CA-19-9 Antigen; Carcinoembryonic Antigen; Humans; Immunoenzyme Techniques; Male; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms

A substantial subset of breast, colorectal, ovarian, endometrial and prostatic cancers displays markedly elevated expression of immunohistochemically detectable fatty acid synthase, a feature that has been associated with poor prognosis and that may be exploited in anti-neoplastic therapy. Here, using an RNA array hybridisation technique complemented by in situ hybridisation, we report that in prostate cancer fatty acid synthase expression is up-regulated at the mRNA level together with other enzymes of the same metabolic pathway. Contrary to the observations that in many cell systems (including androgen-stimulated LNCaP prostate cancer cells) fatty acid and cholesterol metabolism are co-ordinately regulated so as to supply balanced amounts of lipids for membrane biosynthesis, storage or secretion, no changes in the expression of genes involved in cholesterol synthesis were found. These findings point to selective activation of the fatty acid synthesis pathway and suggest a shift in the balance of lipogenic gene expression in a subgroup of prostate cancers.

Topics: Acetyl-CoA Carboxylase; Acid Phosphatase; Fatty Acid Synthases; Gene Expression Regulation, Enzymologic; Gene Expression Regulation, Neoplastic; Humans; Hydroxymethylglutaryl CoA Reductases; In Situ Hybridization; Male; Peptides; Prostate; Prostatic Hyperplasia; Prostatic Neoplasms; Prostatic Secretory Proteins; Reference Values; RNA, Messenger; Transcription, Genetic

Androgens regulate the expression of both human prostatic acid phosphatase (PAcP) and prostate-specific antigen (PSA), two major prostate epithelium-specific differentiation antigens. Due to the important role of these two enzymes as prostate epithelium differentiation markers, we investigated their regulation of expression at the mRNA level in LNCaP human prostate carcinoma cells. Interestingly, phenol red, a pH indicator in the culture medium, promoted cell growth. To eliminate this non-specific effect, a phenol red-free, steroid-reduced medium was utilized. When high-density cells were grown in that medium, 5alpha-dihydrotestosterone (DHT) suppressed PAcP but stimulated PSA. However, tumor promoter phorbol ester 12-o-tetradecanoyl phorbol-13-acetate (TPA) functioned as a potent inhibitor of both PAcP and PSA expression. Prolonged treatment with DHT as well as TPA resulted in a similar down-regulation of protein kinase C and cellular PAcP activities. Thus, the levels of PAcP and PSA mRNA are differentially regulated by androgens in LNCaP cells.

Topics: Acid Phosphatase; Androgens; Carcinogens; Cell Division; Dihydrotestosterone; Humans; Male; Phenolsulfonphthalein; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Protein Kinase C; RNA, Messenger; Tetradecanoylphorbol Acetate; Tumor Cells, Cultured

Several immune based therapies targeting prostate cancer associated proteins are currently undergoing clinical investigation. In general, however, little is known about the immunogenicity of prostate cancer or which prostate cancer associated proteins elicit immune responses. We determine whether patients with prostate cancer have antibody immunity to known prostate cancer associated proteins, what the prevalence of this immunity is and whether immunity to individual proteins is associated with the stage of disease.. We evaluated the inherent humoral immune response against prostate specific antigen (PSA), prostatic acid phosphatase, p53 and HER-2/neu, all known prostate cancer associated proteins, in 200 patients with various stages of disease and male controls.. Antibody immunity to PSA was significantly different between the patient (11%, 22 of 200) and control populations (1.5%, 3 of 100, p = 0.02), and titers 1:100 or greater were particularly prevalent in the subgroup of patients with androgen independent disease (11%, 6 of 56). Antibody immunity to prostatic acid phosphatase and p53 was detected (5.5%, 11 of 200 and 6%, 12 of 200), and was not different from the control population (4%, 4 of 100, p = 0.57 and 7%, 7 of 100, p = 0.74). Antibody immunity to HER-2/neu was significantly higher in patients with prostate cancer (15.5%, 31 of 200) compared to controls (2%, 2 of 100, p = 0.0004), and titers 1:100 or greater were most prevalent in the subgroup of patients with androgen independent disease (16%, 9 of 56).. These findings suggest that prostate cancer is an immunogenic tumor. Moreover, for PSA and HER-2/neu the prevalence of antibody immunity was higher in patients with androgen independent disease, indicating that even patients with advanced stage prostate cancer can have an immune response to their tumor.

Topics: Acid Phosphatase; Adult; Aged; Antibody Formation; Antigens, Neoplasm; Enzyme-Linked Immunosorbent Assay; Humans; Male; Middle Aged; Oncogene Proteins v-erbB; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Tumor Suppressor Protein p53

To explore the potential role of a neural network-derived algorithm in enhancing the specificity of prostate cancer detection compared with the determination of prostate-specific antigen (PSA) and free PSA (fPSA) while maintaining a 90% detection rate. Recent information suggests that the incidence of detectable prostate cancer is similar in men whose PSA values range from 2.5 to 4.0 ng/mL and from 4.0 to 10.0 ng/mL. If the PSA threshold triggering a prostate biopsy is lowered to 2.5 ng/mL, approximately 13% of men older than 50 would be added to the patient biopsy pool.. One hundred fifty-one men were enrolled in a prospective, Institutional Review Board-approved protocol to evaluate the incidence of cancer in a population of men who participated in an early-detection program and whose PSA level was between 2.5 and 4.0 ng/mL. All the men underwent biopsy using an 11-core multisite-directed biopsy scheme, and all biopsy specimens were examined by one pathologist. All men had a second blood specimen drawn before the biopsy for a determination of serum PSA, creatinine kinase, prostatic acid phosphatase, and fPSA. A new neural network algorithm was developed with PSA, creatinine kinase, prostatic acid phosphatase, fPSA, and age as input variables to produce a single-valued prostate cancer detection index (PCD-I). This new algorithm was then prospectively tested in the 151 men. Performance parameters (including sensitivity, specificity, positive and negative predictive values, and biopsies saved) were calculated, and a comparative analysis was performed to evaluate the differences among the new algorithm, percent fPSA, PSA density, and PSA density-transition zone.. Cancer was histologically confirmed in 24.5% (37 of 151) of the men. The median age of the men was 62 years (range 43 to 74). At a sensitivity of 92%, the specificity for percent fPSA was 11%. The new algorithm (PCD-I) demonstrated an additional enhancement of specificity to 62% at 92% sensitivity. Clinically, the PCD-I would result in a savings of 49% (74 of 151) of all biopsies or 63.6% (71 of 114) of all unnecessary biopsies.. A new generation algorithm, derived from a neural network (PCD-I) incorporating the parameters of age, creatinine kinase, PSA, prostatic acid phosphatase, and fPSA can significantly enhance the specificity and reduce the number of biopsies while maintaining a 92% sensitivity rate.

Topics: Acid Phosphatase; Adult; Age Factors; Aged; Algorithms; Biopsy; Creatine Kinase; Humans; Male; Middle Aged; Neural Networks, Computer; Prospective Studies; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Sensitivity and Specificity

In a retrospective study we examined whether follow-up of prostate cancer (PC) patients can be managed by using prostate-specific antigen (PSA) as a unique tool as postulated recently.. According to strict criteria established in the eighties, at our institution PC patients were monitored by PSA, prostatic acid phosphatase (PAP), alkaline phosphatase (AP), digital-rectal examination, renal and bladder ultrasound every 3 months, abdominopelvic computerized tomography (CT) and bone scan every 6 months. Between 1988 and 1994, 80 patients with PC cancer were eligible (mean follow-up 29.5, range 12-81 months). Patients were categorized into 4 groups: localized tumor (n = 44); lymph node metastases (n = 9); distant metastases (n = 18), and lymph node and distant metastases (n = 9). The parameters mentioned were compared for the assessment of progression, regression and stabilization of the disease.. Our examinations showed that PSA is superior to all the other parameters used. In all groups, there were no patients with progressive disease detected by PAP, AP, CT and bone scan, but not by PSA. PSA anticipated the other parameters in detecting progression by several months. Renal ultrasound, however, detected new hydronephrosis in 6 patients with stable or decreasing PSA. Hydronephrosis was caused by surgery or radiotherapy, not by progressive PC.. PSA can be used as a unique tool in the follow-up of PC patients in all stages. However, patients who underwent therapy potentially afflicting the urinary tract should have additional renal and bladder ultrasound.

Topics: Acid Phosphatase; Adult; Aged; Aged, 80 and over; Alkaline Phosphatase; Biomarkers, Tumor; Bone and Bones; Disease Progression; Follow-Up Studies; Humans; Kidney; Male; Middle Aged; Pelvis; Predictive Value of Tests; Prostate-Specific Antigen; Prostatic Neoplasms; Radiography, Abdominal; Radionuclide Imaging; Tomography, X-Ray Computed; Ultrasonography; Urinary Bladder

Immunohistochemistry with antibodies for high-molecular-weight cytokeratin labels basal cells and is used as an ancillary study in diagnosing prostate carcinoma, which reportedly lacks expression of high-molecular-weight cytokeratin. A recent report questioned the specificity of this marker, describing immunopositivity for high-molecular-weight cytokeratin in a small series of metastatic prostate cancer. We have also noted rare cases of prostate lesions on biopsy with typical histological features of adenocarcinoma showing immunopositivity for high-molecular-weight cytokeratin, either in tumor cells or in patchy cells with the morphology of basal cells. In some of these cases, it was difficult to distinguish cancer from out-pouching of high-grade prostatic intraepithelial neoplasia. To investigate whether prostate cancer cells express high-molecular-weight cytokeratin, we studied 100 cases of metastatic prostate carcinoma and 10 cases of prostate cancer invading the seminal vesicles from surgical specimens. Metastatic sites included regional lymph nodes (n = 67), bone (n = 19), and miscellaneous (n = 14). Cases with any positivity for high-molecular-weight cytokeratin antibody (34betaE12) were verified as being of prostatic origin with immunohistochemistry for prostate-specific antigen and prostate-specific acid phosphatase. Only four cases were detected positive for high-molecular-weight cytokeratin. In two cases (one metastasis, one seminal vesicle invasion) there was weakly diffuse positivity above background level. Two metastases in lymph nodes showed scattered strong staining of clusters of tumor cells, which represented <0.2% of tumor cells in the metastatic deposits. These positive cells did not have the morphology of basal cells. We conclude that prostate cancer, even high grade, only rarely expresses high-molecular-weight cytokeratin. This marker remains a very useful adjunct in the diagnosis of prostate cancer.

Topics: Acid Phosphatase; Adenocarcinoma; Biomarkers, Tumor; Humans; Immunoenzyme Techniques; Keratins; Male; Molecular Weight; Neoplasm Metastasis; Prostate-Specific Antigen; Prostatic Neoplasms; Seminal Vesicles

To evaluate the outcome of clinical Stage III (T3, N0/NX, M0) prostate cancer treated by conventional radiation alone or with adjuvant androgen ablation.. Three hundred forty-four men with T3, N0/NX, M0 adenocarcinoma of the prostate who received conventional radiation alone (260) or with androgen ablation (84) were analyzed for relapse or rising prostate-specific antigen (PSA), using univariate and multivariate techniques.. With a median follow-up of 68 months, the 260 men treated with radiation alone had a 10-year actuarial rate of relapse or rising PSA of 76%. Pretreatment PSA level (< or = 10 ng/ml vs. > 10 < or = 20 ng/ml vs. > 20 ng/ml) and radiation dose (< 68 Gy vs. > or = 68 Gy) were the only independently significant determinants of biochemical failure; Gleason score (2-7 vs. 8-10) was an additional determinant of metastatic relapse. Patients treated to doses < 68 Gy experienced 6-year failure rates exceeding 50% regardless of PSA level. Patients with PSA < or = 10 ng/ml and receiving 68-70 Gy had a 6-year failure of 24%, but those with PSA > 10 ng/ml had relapse rates exceeding 50% even at doses of 70 Gy. At a median follow-up of 44 months, the 84 patients treated with radiation and androgen ablation had a 6-year biochemical failure rate of 22%. The only significant determinant of outcome in this group was pretreatment PSA; patients with PSA < or = 80 ng/ml had a 6-year failure rate of only 12% compared to a failure rate of 53% for those with PSA > 80 ng/ml. The outcome for those treated with combined modalities was significantly better than for those treated with radiation alone in all PSA strata.. Conventional radiation alone has little curative potential for Stage III disease. Doses < 68 Gy are particularly ineffective. Patients with PSA < or = 10 ng/ml may be candidates for conventional radiation to a dose of 70 Gy. Other patients are probably best served by combined radiation-androgen ablation or high-dose conformal radiation.

Topics: Acid Phosphatase; Adenocarcinoma; Aged; Analysis of Variance; Androgen Antagonists; Antineoplastic Agents, Hormonal; Cohort Studies; Combined Modality Therapy; Follow-Up Studies; Gonadotropin-Releasing Hormone; Humans; Male; Neoplasm Recurrence, Local; Neoplasm Staging; Orchiectomy; Prostate-Specific Antigen; Prostatic Neoplasms; Radiotherapy, Conformal

Activities of arginase, prostatic acid phosphatase (PAP) and prostate specific antigen (PSA) were determined in sera of healthy male controls, benign prostatic hypertrophy (BPH) and prostatic cancer patients. Serum arginase activity in the cancer group (22.8+/-11.6 U/l) was significantly lower than in both the control (33.64+/-16.19 U/l) and the BPH group (58.8+/-11.6 U/l) (p<0.001, respectively), while the BPH group had significantly higher levels compared to the controls (p<0.05). However, serum arginase levels in all groups had no statistically significant correlation with PAP and PSA. Serum arginase activity correlated inversely with the Gleason grades. These results suggest that serum arginase assay may be used for the pretreatment evaluation of patients with prostatic diseases.

Topics: Acid Phosphatase; Aged; Arginase; Clinical Enzyme Tests; Humans; Male; Middle Aged; Prostate-Specific Antigen; Prostatic Hyperplasia; Prostatic Neoplasms; Reference Values

Prostatic-specific antigen (PSA) is regarded as a specific marker secreted by normal and neoplastic acinar epithelial cells of the prostate gland; its detection by immunocytochemistry has been accepted as an indication of metastatic prostate cancer. This is ascribed to the commonly held belief that PSA is not found in extraprostatic tissues. However, this concept has recently been challenged, based on the observations that certain nonprostatic tissues and their neoplasms can also secrete PSA. Such a questionable belief could result in a diagnostic pitfall when using immunostaining for PSA on fine-needle aspiration (FNAC) cytology samples to differentiate metastatic prostate cancer from a primary carcinoma of an extraprostatic organ. In this communication, two cases of primary carcinomas of the male breast are reported in which PSA immunopositivity on FNAC led to the suggestion of a diagnosis of metastatic carcinoma of the prostate. Diagn. Cytopathol. 1999;21:167-169.

Topics: Acid Phosphatase; Aged; Aged, 80 and over; Biopsy, Needle; Breast Neoplasms, Male; Carcinoembryonic Antigen; Diagnosis, Differential; Humans; Immunoenzyme Techniques; Male; Neoplasm Metastasis; Prostate-Specific Antigen; Prostatic Neoplasms

To establish the prognostic role of serum enzymatic prostatic acid phosphatase (PAP) in patients treated with palladium (103Pd) and supplemental external beam irradiation (EBRT) for clinically localized, high-risk prostate carcinoma.. One hundred twenty-four consecutive patients with Stage T2a-T3 prostatic carcinoma were treated from 1992 through 1995. Each patient had at least one of the following risk factors for extracapsular disease extension: Stage T2b or greater (100 patients), Gleason score 7-10 (40 patients), pretreatment prostate specific antigen (PSA) >15 ng/ml (32 patients), or elevated serum PAP (25 patients). Patients received 41 Gy conformal EBRT to a limited pelvic field, followed 4 weeks later by a 103Pd boost (prescription dose 80 Gy). Biochemical failure was defined as a PSA greater than 1 ng/ml (normal <4 ng/ml).. The overall, actuarial freedom from biochemical failure at 4 years after treatment was 79%. In Cox-proportional hazard multivariate analysis, the strongest predictor of failure was elevated pretreatment acid phosphatase (p = 0.02), followed by Gleason score (p = 0.1), and PSA (p = 0.14).. PAP was the strongest predictor of long-term biochemical failure. It may be a more accurate indicator of micrometastatic disease than PSA, and as such, we suggest that it be reconsidered for general use in radiation-treated patients.

Topics: Acid Phosphatase; Aged; Aged, 80 and over; Brachytherapy; Humans; Male; Middle Aged; Multivariate Analysis; Neoplasm Proteins; Neoplasm Staging; Palladium; Prognosis; Prostate-Specific Antigen; Prostatic Neoplasms; Radioisotopes; Treatment Failure

Topics: Acid Phosphatase; Biomarkers, Tumor; Humans; Male; Neoplasm Staging; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; ROC Curve; Sensitivity and Specificity

Prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP) are well known as specific tumor markers of prostate cancer, but carcinoembryonic antigen (CEA)- and carbohydrate antigen 19-9 (CA19-9)-producing adenocarcinoma originating in the prostate is rare. We report here a case of prostatic adenocarcinoma positive for these 4 tumor markers in a 50-year-old man who had initially complained about chest pain due to metastatic bone tumor. In spite of the extensive treatment involving hormone and radiation therapy, the patient died of rapid tumor extension only 4 months after initial diagnosis. Autopsy revealed multiple metastases to the bone, liver, lungs and lymph nodes. Histologically, two types of adenocarcinoma were involved in both primary prostate and metastatic sites: one was a poorly differentiated adenocarcinoma positive for PSA and PAP but not CEA or CA19-9, and the other one was a less differentiated adenocarcinoma partially positive for CEA and CA19-9 but not for PSA or PAP. Based on this case and previous cases by review of the literature, CEA- and CA19-9-producing adenocarcinoma of the prostate was suggested to rapidly progress with multiple metastases and to show poor prognosis with strong resistance to any treatment.

Topics: Acid Phosphatase; Adenocarcinoma; Biomarkers, Tumor; CA-19-9 Antigen; Carcinoembryonic Antigen; Humans; Male; Middle Aged; Prognosis; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms

Topics: Acid Phosphatase; Aged; Androgen Antagonists; Antineoplastic Agents, Hormonal; Biopsy; Flutamide; Goserelin; Humans; Male; Middle Aged; Prostate-Specific Antigen; Prostatectomy; Prostatic Neoplasms

Although, in general, immunoperoxidase staining for prostate-specific antigen (PSA) and prostate-specific acid phosphatase (PSAP) cannot distinguish between benign and malignant prostatic epithelium, immunoreactivity of these antigens may be helpful in predicting prognosis of prostate cancer. The purpose of this study was to evaluate intensity and extent of immunoperoxidase staining for PSA and PSAP as a prognostic tool in prostate adenocarcinomas.. We studied radical prostatectomy specimens from 68 patients with the following stages: organ-confined, 34.3%; focal capsular penetration, 38.8%; established capsular penetration, 25.3%; and seminal vesicle invasion, 1.6%. Ninety-one percent of cases were Gleason score 5-7. The mean follow-up for those men without progression was 8.9 years, compared to 3.5 years for those with progression. Progression was defined as an elevated postoperative serum PSA level (> 0.2 ng/ml). Intensity of PSA and PSAP staining was recorded and based on a scale of 0-3 (0, no staining; 1, weak; 2, moderate; 3, intense). Extent was quantitated on a scale of 0-4 (0, 0-5% staining; 1, 6-35%; 2, 36-65%; 3, 65-95%; 4, 95-100%). A score (0-12) was computed by multiplying intensity and extent of the stain in the tumor area.. Intensity and extent of PSA and PSAP immunoreactivity did not predict progression in adenocarcinomas of the prostate following radical prostatectomy.

Topics: Acid Phosphatase; Adenocarcinoma; Biomarkers, Tumor; Disease Progression; Humans; Immunoenzyme Techniques; Male; Prostate; Prostate-Specific Antigen; Prostatectomy; Prostatic Neoplasms

To confirm the expression of prostate specific antigen (PSA) and prostatic acid phosphatase (PAP) in ductal carcinomas of the prostate, and to analyse p53, Ki67, oestrogen (ER) and androgen (AR) receptors in these tumours.. Paraffin-embedded samples from 12 patients with ductal carcinoma of the prostate were assessed for pattern, mitotic count and the presence of a microacinar carcinoma component. There were six pure ductal and six mixed microacinar and ductal carcinomas. Sections were stained immunohistochemically for the expression of PSA, PAP, Ki67, p53, AR and ER. Clinical data were obtained from case notes.. Six of the ductal tumours had a papillary pattern whilst the others had a cribriform appearance. The mitotic rates in the ductal areas were high in the tumours from eight of the 12 patients. PSA and PAP immunohistochemistry were positive in all the cases. No ER immunoreactivity was found in any of the patients. Ten of the ductal tumours showed strong reactivity with AR, the other two were weakly positive; two of the tumours were strongly positive for p53 protein. All the ductal carcinomas expressed Ki67, three having > 25% nuclear marking. One patient who was strongly positive for p53 and had a high Ki67 score survived only one year after diagnosis. Survival ranged from 1 to 13 years after diagnosis.. This study confirms the expression of PSA and PAP in ductal carcinomas of the prostate. The percentage of tumours expressing p53 was similar to that published for high-grade microacinar carcinomas. The results for Ki67 suggest that ductal tumours have higher scores than microacinar tumours, but further studies are required to ascertain if this is significantly different. As half the patients with ductal tumours had co-existent microacinar tumours, we advise transrectal prostatic biopsies in patients diagnosed with pure ductal carcinomas on transurethral resection specimens, to exclude high-grade microacinar carcinomas. The presence of AR and the lack of ER in all the ductal carcinomas confirms that these tumours are prostatic in origin and should be treated with antiandrogen therapy.

Topics: Acid Phosphatase; Aged; Aged, 80 and over; Carcinoma; Humans; Immunohistochemistry; Ki-67 Antigen; Male; Neoplasm Proteins; Orchiectomy; Prostatectomy; Prostatic Neoplasms; Tumor Suppressor Protein p53

We examine the clinical prognostic value of the currently available simple and inexpensive immunoenzymatic prostatic acid phosphatase (PAP) assay for the staging and prognosis of radical prostatectomy cases.. Between February 1, 1990 and May 3, 1996 pretreatment PAP was measured in 295 patients who underwent radical prostatectomy. From February 1, 1990 to May 17, 1992 the Hybritech Tandem-E assay was used in 75 cases, from May 18, 1992 to February 28, 1993 the Abbott EIA assay was used in 49 and from March 1, 1993 to May 3, 1996 the Abbott IMx assay was used in 171. PAP assays were analyzed individually and the results were combined with pretreatment prostate specific antigen (PSA) values to assess the ability to predict organ confined prostate cancer and serological recurrence after radical prostatectomy.. PAP testing was not of value for predicting organ confined disease or positive margins. However, this test was useful for predicting the first serological PSA recurrence in the 3 periods (77 to 85% correct) and overall (82% correct, p < 0.001, odds ratio 6.06). The Kaplan-Meier disease-free survival rate at 4 years was 78.8% for men with PAP less than 3 ng./ml. and 38.8% for those with PAP 3 ng./ml. or greater, which was significant when pretreatment PSA was less than 10 ng./ml. (p = 0.047), 10 ng./ml. or greater (p = 0.012) and overall (p < 0.001). PAP testing added prognostic information to pretreatment PSA values and it was an independent predictor of recurrence.. The widely available and inexpensive PAP assays of the 1990s are predictors of recurrence after radical prostatectomy. They should be included in future studies of prostate cancer recurrence modeling. However, they do not predict pathological stage or margin status.

Topics: Acid Phosphatase; Aged; Biomarkers, Tumor; Humans; Immunoenzyme Techniques; Logistic Models; Male; Middle Aged; Multivariate Analysis; Neoplasm Metastasis; Neoplasm Staging; Predictive Value of Tests; Prognosis; Proportional Hazards Models; Prostate; Prostatectomy; Prostatic Neoplasms; Retrospective Studies; Sensitivity and Specificity; Survival Analysis

Androgen plays a critical role in regulating the growth and differentiation of normal prostate epithelia, as well as the initial growth of prostate cancer cells. Nevertheless, prostate carcinomas eventually become androgen-unresponsive, and the cancer is refractory to hormonal therapy. To gain insight into the mechanism involved in this hormone-refractory phenomenon, we have examined the potential role of the androgen receptor (AR) in that process. We have investigated the expression of AR and two prostate-specific androgen-responsive antigens, prostatic acid phosphatase (PAcP) and prostate-specific antigen (PSA), for the functional activity of AR in LNCaP and PC-3 human prostate carcinoma cells. Our results are as follows. (i) Clone 33 LNCaP cells express AR, PAcP, and PSA, and cell growth is stimulated by 5alpha-dihydrotestosterone (DHT). Stimulation of cell growth correlates with decreased cellular PAcP activity. (ii) In clone 81 LNCaP cells, the expression of PAcP decreases with a concurrent decrease in the degree of androgen stimulation of cell growth, whereas the expression of PSA mRNA level is up-regulated by DHT, as in clone 33 cells. Conversely, in PAcP cDNA-transfected clone 81 cells, an additional expression of cellular PAcP correlates with an increased stimulation by androgen, higher than the corresponding control cells. (iii) PC-3 cells express a low level of functional AR with no detectable PAcP or PSA, and the growth of PC-3 cells is not affected by DHT treatment. Nevertheless, in two PAcP cDNA-transfected PC-3 sublines, the expression of exogenous cellular PAcP correlates with androgen stimulation. This androgen stimulation of cell growth concurs with an increased tyrosine phosphorylation of a phosphoprotein of 185 kDa. In summary, the data indicate that the expression of AR alone is not sufficient for androgen stimulation of cell growth. Furthermore, in AR-expressing prostate cancer cells, the expression of cellular PAcP correlates with androgen stimulation of cell proliferation.

Topics: Acid Phosphatase; Androgens; Cell Division; Gene Expression Regulation, Neoplastic; Humans; Male; Phosphoprotein Phosphatases; Phosphorylation; Phosphotyrosine; Prostate-Specific Antigen; Prostatic Neoplasms; Receptors, Androgen; RNA, Messenger; Testosterone; Transfection; Tumor Cells, Cultured; Up-Regulation

Laparoscopic pelvic lymphadenectomy (LPLND) can be performed safely and with minimal morbidity in the staging of prostate cancer. Its utility in evaluating patients at high risk for metastatic disease before primarily nonsurgical treatment modalities was evaluated.. Twenty-four consecutive patients who underwent LPLND between June 1993 and July 1996 were studied. These patients were considered poor surgical candidates based on several risk factors, as follows: elevation of serum PSA >20 in 19 patients (79%); elevation of serum acid phosphatase in 4 patients (17%); digital rectal examination findings indicative of extraprostatic extension or seminal vesical involvement in 14 patients (58%); and poorly differentiated tumors on prostate biopsy in 19 patients (79%). Nineteen patients (79%) had two or more of these risk factors. Median PSA for the entire series of patients was 35.2 ng/mL (range 7.9 to 133 ng/mL), and median Gleason score was 7 (range 5 to 9). Preoperative CT or MRI was negative for pelvic lymph node metastases in 17 of 23 patients (79%), and bone scan was negative in all 24 patients.. Unilateral (n = 2) or bilateral (n = 22) LPLND was performed in all patients. Six patients (25%) had lymph node metastases detected laparoscopically. Five of the six patients had palpable extraprostatic extension (T3a/b) or invasion of a seminal vesical (T3c), and in four of these patients the site of the metastatic lymph nodes was ipsilateral to the palpable prostate abnormality. None of the risk factors was independently predictive of lymph node metastases within this series of patients. An average of 10.8 +/- 6.5 lymph nodes was removed at a mean operative time of 174 +/- 10 minutes for patients undergoing bilateral LPLND. Estimated blood loss was minimal for 20 of 22 patients (92%) undergoing LPLND alone, and there were no complications requiring open exploration. Mean postoperative hospital stay was 1.2 +/- 0.5 days for patients undergoing LPLND alone.. LPLND can be used efficiently to identify patients with nodal metastases from select high-risk patients. This, in turn, can exclude such patients from noncurative local and regional therapy.

Topics: Acid Phosphatase; Biomarkers, Tumor; Biopsy; Blood Loss, Surgical; Bone and Bones; Evaluation Studies as Topic; Follow-Up Studies; Forecasting; Hospitalization; Humans; Intraoperative Complications; Laparoscopy; Length of Stay; Lymph Node Excision; Lymphatic Metastasis; Magnetic Resonance Imaging; Male; Middle Aged; Neoplasm Invasiveness; Neoplasm Staging; Pelvis; Physical Examination; Postoperative Complications; Prostate-Specific Antigen; Prostatic Neoplasms; Radionuclide Imaging; Risk Factors; Safety; Seminal Vesicles; Time Factors; Tomography, X-Ray Computed

Human prostatic acid phosphatase (PAP) has been proposed to be a prostate-epithelium differentiation antigen and its expression can be regulated by androgen. Nevertheless, the regulatory mechanism at the molecular level is not completely understood. In this communication, we demonstrated the tissue-specific expression of PAP in the normal prostate epithelium. Furthermore, results of nuclear run-on experiments indicated that androgen could regulate the transcriptional rate of the PAP gene. This mode of regulation was modulated by cell density. To investigate the transcriptional regulation, we cloned and characterized a 1.4- kilobase (kb) fragment of DNA that flanks the 5' region of the PAP gene from LNCaP human prostate carcinoma cells. The results demonstrated that this 1. 4-kb DNA fragment can drive a chloramphenicol acetyltransferase (CAT) gene expression in LNCaP cells. Also, the promoter activity was inversely correlated with the growth of those cells.

Topics: Acid Phosphatase; Androgens; Cell Division; Chloramphenicol O-Acetyltransferase; Cloning, Molecular; Culture Media; Gene Expression Regulation, Enzymologic; Humans; Male; Promoter Regions, Genetic; Prostatic Neoplasms; RNA, Messenger; Transcription, Genetic; Tumor Cells, Cultured

The Dunning H rat prostate tumor (R3327H) is a widely used experimental model of human prostatic adenocarcinoma (CaP). The Dunning H tumor has been characterized as androgen-sensitive, androgen-receptor (AR) positive, prostate-specific antigen and prostatic acid phosphatase (PAP) positive. To date, the tumor has been maintained by serial passage in vivo because of the lack of an in vitro cell line that retains the characteristics of the in vivo tumor. The objective of the present study was to establish a propagable cell line from R3327H adenocarcinoma that maintained androgen sensitivity and expression of AR, PSA and PAP. Tissue harvested from an in vivo R3327H tumor was dissociated with collagenase and placed into Richter's improved media (with supplements). A cytokeratin-positive epithelial cell line (HUNC-E) and a vimentin-positive stromal cell line (HUNC-S) were generated from the primary culture, subcultured continuously for >300 days, and passaged >50 times. Survival of the HUNC-E cell line in vitro depended on several media supplements, including nicotinamide, insulin, transferrin, selenium and epidermal growth factor (EGF). HUNC-E cells expressed AR and produced PSA and PAP throughout the culture period, as confirmed by immunocytochemistry and Western blot analyses. Addition of 14 nM testosterone (T) or dihydrotestosterone (DHT) to HUNC-E cells, stimulated DNA synthesis as well as anchorage-independent growth and PSA production, which demonstrated the androgen-sensitive nature of the cells in vitro. When HUNC-E and HUNC-S cells were combined in a 3:1 ratio and introduced subcutaneously into syngeneic male hosts, tumors formed in 2/3 animals with an average latency of 7 months. RT-PCR and immunocytochemical characterization of the HUNC cell lines revealed that the cells expressed several growth factors and their cognate receptors, including HGF, TGF-alpha and the TGF-betas, indicating the establishment of potential autocrine loops in the neoplastic cells. The HUNC-E and HUNC-S CaP cell lines, which retain the characteristics of the epithelial and stromal components of the in vivo R3327H tumor, will allow a more thorough and informative molecular and biological analysis of prostatic adenocarcinoma.

Topics: Acid Phosphatase; Adenocarcinoma; Androgens; Animals; Cell Division; Humans; Immunohistochemistry; Male; Polymerase Chain Reaction; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Rats; Receptors, Androgen; Tumor Cells, Cultured

The osteolytic activity of metastases of prostate cancer was evaluated in relation to total body bone mineral content (TBBMC) and regional bone mineral content (RBMC).. Bone mass was determined by dual-energy X-ray absorptiometry (DXA). Tartrate-resistant acid phosphatase (TRAP) was measured as a biochemical marker of bone resorption.. In 32 patients (mean age 72+/-4 years) compared with 32 controls (mean age 73+/-5 years), there were significant differences in TRAP (P < 0.0001), TBBMC (P < 0.0001), and RBMC in the pelvis (P < 0.0001), legs (P=0.0001), and trunk (P<0.05), but not in the arms and head (P=ns). In the overall group of subjects, the correlation between TBBMC and TRAP was r=-0.68, P < 0.0001. The correlations remained significant in the patient and control groups separately.. The loss of bone mass observed in patients with metastatic prostate cancer was caused mainly by the predominance of bone resorption in the osteoblastic metastases.

Topics: Absorptiometry, Photon; Acid Phosphatase; Aged; Alkaline Phosphatase; Analysis of Variance; Biomarkers; Bone Density; Bone Neoplasms; Bone Remodeling; Bone Resorption; Calcium; Humans; Isoenzymes; Male; Neoplasm Metastasis; Prostatic Neoplasms; Reference Values; Regression Analysis; Tartrate-Resistant Acid Phosphatase

Most strategies in cancer immunotherapy are aimed at the induction of a strong cellular immune response against the tumor. Particularly, CD8+ T lymphocytes have been proven in multiple animal models to be critical for the eradication of solid tumors.. We used a population of peripheral blood-derived antigen-presenting cells (APC), containing dendritic cells (DC), to generate prostate tumor-specific CD8+ T cells. Selected peptides from prostatic acid phosphatase (PAP), a prostate tissue-specific antigen, were shown to bind HLA-A2. A high-affinity peptide was used to generate peptide-specific CD8+ cytolytic T lymphocytes (CTL) from the peripheral blood of healthy donors.. The obtained PAP-peptide-specific CTL lysed peptide-coated target cells, vaccinia-infected target cells, and HLA-A2-positive prostate-tumor cells in vitro in an antigen-specific manner.. Our results indicate that CTL precursors to the PAP gene product exist and could be potentially recruited to elicit an antitumor response. Thus, PAP is a suitable antigen for inclusion in prostate cancer vaccines.

Topics: Acid Phosphatase; Antigen-Presenting Cells; CD8-Positive T-Lymphocytes; Cytotoxicity, Immunologic; Dendritic Cells; HLA-A2 Antigen; Humans; Male; Peptide Fragments; Prostate; Prostatic Neoplasms

Hormone-refractory prostate cancer (HRPC) patients often have nonmeasurable disease. In such patients, predictive biomarkers other than tumor response may be required to compare therapeutic effects. We examined the predictive value for survival of various clinical and laboratory parameters, including prostate-specific antigen (PSA), in HRPC patients treated with suramin. Data from 103 HRPC patients were analyzed using various survival analyses, the likelihood ratio approach, and logistic regression analyses. When pretreatment factors, percentage decrease in PSA at 4 weeks from start of treatment (deltaPSA), and updated survival data were fit by a multivariate Cox proportional hazards model, acid phosphatase, lactate dehydrogenase, and deltaPSA were significant, with risk ratios close to 1. There was a decrease in likelihood ratio with increasing APSA. A logistic regression model was developed to predict the probability of <1 year of survival from the start of treatment. Hemoglobin and deltaPSA were found to be significant variables. However, in view of the complexities involving the relationship between PSA expression and prostate cancer growth and possible selective effect of treatment on PSA, further prospective testing is necessary. Therefore, deltaPSA cannot necessarily be used as a biomarker for survival response in individual patients during the evaluation of the therapeutic response of HRPC to new antineoplastic drugs.

Topics: Acid Phosphatase; Adult; Aged; Aged, 80 and over; Analysis of Variance; Antineoplastic Agents; Biomarkers, Tumor; Hemoglobin A; Humans; L-Lactate Dehydrogenase; Male; Middle Aged; Proportional Hazards Models; Prostate-Specific Antigen; Prostatic Neoplasms; Suramin

To describe patterns and trends in prostate-specific antigen (PSA) testing in Australia and assess its role in the increasing incidence of prostate cancer.. Descriptive analysis of (i) Medicare records of PSA testing in Australia, and (ii) prostate cancer recorded incidence in New South Wales.. (i) Medicare data for all males who received a Medicare-reimbursed PSA test between August 1989 and December 1996. (ii) NSW Central Cancer Registry data for all males in NSW with prostate cancer diagnosed between 1988 and 1995.. (i) Number of PSA tests, age-standardised rates of PSA tests by State and Territory, and proportions of males who had a PSA test. (ii) Recorded incidence of prostate cancer in NSW.. (i) More than 2.2 million PSA tests were done on more than 1.1 million Australians between 1989 and 1996. The annual number of males tested increased fivefold in this period and peaked in 1995. Twenty-seven per cent of Australian men aged 50 years or over had at least one PSA test in 1995 or 1996; 33% of men aged 60-69 years had a test in this period. (ii) In NSW the number of PSA tests per quarter was highly correlated with the number of new cases of prostate cancer (R2 = 0.92).. Although no organised program for prostate cancer screening exists, and despite repeated advice against it, opportunistic screening has been occurring at high rates. There was a high correlation between PSA testing and prostate cancer incidence between 1990 and 1995 in NSW.

Topics: Acid Phosphatase; Adolescent; Adult; Aged; Aged, 80 and over; Child; Child, Preschool; Hematologic Tests; Humans; Incidence; Infant; Infant, Newborn; Male; Middle Aged; New South Wales; Prostate-Specific Antigen; Prostatic Neoplasms

Human prostatic acid phosphatase (PAcP) is a prostate epithelium-specific differentiation antigen. In prostate carcinomas, the cellular PAcP is decreased. We investigated its functional role in these cells. Several lines of evidence support the hypothesis that cellular PAcP functions as a neutral protein-tyrosine phosphatase and is involved in regulating prostate cell growth. In this study, we identify its in vivo substrate. Our results demonstrated that, in different human prostate cancer cell lines, the phosphotyrosine (Tyr(P)) level of a 185-kDa phosphoprotein (pp185) inversely correlates with the cellular activity of PAcP. On SDS-PAGE, this pp185 co-migrates with the c-ErbB-2 oncoprotein. Immunodepletion experiments revealed that c-ErbB-2 protein is the major pp185 in cells. Results from subclones of LNCaP cells indicated the lower the cellular PAcP activity, the higher the Tyr(P) levels of c-ErbB-2. This inverse correlation was further observed in PAcP cDNA-transfected cells. In clone 33 LNCaP cells, L-(+)-tartrate suppresses the cellular PAcP activity and causes an elevated Tyr(P) level of c-ErbB-2 protein. Epidermal growth factor stimulates the proliferation of LNCaP cells, which concurs with a decreased cellular PAcP activity as well as an increased Tyr(P) level of c-ErbB-2. Biochemically, PAcP dephosphorylates c-ErbB-2 at pH 7.0. The results thus suggest that cellular PAcP down-regulates prostate cell growth by dephosphorylating Tyr(P) on c-ErbB-2 oncoprotein in those cells.

Topics: Acid Phosphatase; Humans; Male; Molecular Weight; Phosphorylation; Prostate; Prostatic Neoplasms; Receptor, ErbB-2; Tartrates; Tumor Cells, Cultured; Tyrosine

A 63-year-old man, who had undergone prostatectomy for prostate cancer that was positive for prostate-specific antigen (PSA) was examined and found to have metastatic disease, proven radiologically and pathologically, but with an undetectable PSA and highly elevated prostatic acid phosphatase (PAP). Prostatic acid phosphatase levels fell in response to chemotherapy but his clinical status continued to deteriorate. A review of the literature is presented and several possible explanations for PSA remaining undetectable in these situations are discussed. The authors conclude that although PSA can be used to monitor the majority of patients postprostatectomy, physicians may still need to rely on clinical suspicion, serum PAP, and bone scan for the detection of recurrent disease.

Topics: Acid Phosphatase; Adenocarcinoma; Bone Neoplasms; Humans; Male; Middle Aged; Prostate; Prostate-Specific Antigen; Prostatectomy; Prostatic Neoplasms

Prostate-specific antigen (PSA) is secreted by both normal and neoplastic acinar cells of the prostate gland, and the immunohistochemical detection of PSA is widely accepted as an excellent method for confirming the prostatic origin of metastatic tumor implants in men with prostate cancer. Less recognized is the observation that certain nonprostatic tissues and their neoplastic counterparts also secrete PSA. As one example, salivary gland ducts and certain salivary gland neoplasms have been reported to be immunoreactive for PSA. Potentially, this nonspecificity could be a diagnostic pitfall when using immunoperoxidase on fine-needle aspiration (FNA) biopsy specimens to differentiate metastatic prostate cancer from primary salivary gland tumors. We report on a case where strong PSA immunoreactivity of a parotid oncocytoma led to its confusion with metastatic prostate cancer.

Topics: Acid Phosphatase; Adenocarcinoma; Adenoma, Oxyphilic; Aged; Diagnostic Errors; Humans; Immunoenzyme Techniques; Male; Parotid Neoplasms; Prostate-Specific Antigen; Prostatic Neoplasms

To obtain evidence of metabolic changes in the human prostate associated with prostate pathology, in particular carcinoma of the prostate, by identifying and evaluating associated changes in prostatic secretory products.. Expressed prostatic fluid (EPF) from 36 patients with carcinoma, 128 with BPH histologically confirmed, and 148 with clinical BPH was subjected to determination of protein (Lowry; UV 280 nm absorption), enzymatic (DMA modified Row procedure) acid phosphatase (AcP), and immunologically identified (Tandem-PAP immunoenzymatic assay) prostatic acid phosphatase (PAP) concentration.. The important EPF findings are the following: (1) Protein concentrations (Lowry and UV determinations) are significantly increased in carcinoma as compared to histologic BPH, (2) AcP and PAP secretions remain stable in carcinoma versus BPH, and (3) AcP and PAP/Lowry protein ratios are significantly lower with carcinoma.. These findings of increased protein and the decreased relative secretions of AcP and PAP to total protein (ratio) in EPF from patients with carcinoma compared to BPH support and help to characterize the diffuse metabolic alteration in the prostate associated with prostate carcinoma. EPF observations identify potential metabolic changes occurring in prostate carcinoma that may have potential clinical and investigative relevance.

Topics: Acid Phosphatase; Body Fluids; Humans; Male; Prostate; Prostatic Hyperplasia; Prostatic Neoplasms; Proteins

Topics: Acid Phosphatase; Humans; Male; Prostate-Specific Antigen; Prostatic Neoplasms; Thrombomodulin

Cytoplasmic clarity is a histological feature of normal prostatic secretory cells, but in this study, tissue fixation in strong (>2.5%) glutaraldehyde dramatically altered cytological staining. Secretory cytoplasm appeared red and granular on routine stains because of myriad intensely staining eosinophilic granules (PSG). Immunostaining for prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP) showed their exclusive localization to the PSG. Electron microscopy confirmed these findings and also showed that after fixation in many agents, including formaldehyde, PSG appeared empty, accounting for the artefactual "clear cell" appearance on light microscopy. PSG were most densely concentrated apically in a bud-shaped luminal compartment in which cytokeratin was selectively absent. Normal exocrine secretion was visualized as detachment of apocrine buds or their in situ disintegration. Distinctively in dysplasia and almost all carcinomas, PSG were rare to absent, and proteases were free in the cytoplasm, often concentrated beneath the apical membrane. The apocrine compartment was absent, with no observed secretory mechanism. Tumor cells had dark amphiphilic cytoplasm after all fixatives. This provided a reliable method of distinguishing malignant from benign glands in tissues fixed in strong glutaraldehyde. Clear cell carcinomas, whose cytoplasm mimicked routinely fixed normal secretory cells, surprisingly had almost no PSG. Instead, their "granules" were lipid-filled vacuoles reflecting a secretory pathway not seen in normal cells, dysplasia, or the common "dark cell" carcinomas. These observations may define two distinctive biological pathways of prostate cancer evolution and may facilitate diagnostic decisions on needle biopsy samples.

Topics: Acid Phosphatase; Adenocarcinoma, Clear Cell; Cell Transformation, Neoplastic; Cytoplasmic Granules; Epithelial Cells; Humans; Immunoenzyme Techniques; Male; Precancerous Conditions; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms

To evaluate 3 in vitro methods detection (immunocytochemistry, flow cytometry and RT-PCR PSA) of circulating prostate cancer cells from a model of uncap dilution in immortalised lymphocytes.. In vitro comparison of 3 techniques (immunocytochemistry, flow cytometry, RT-PCR PSA) was performed from a range of dilutions of LbCap cells in immortalised human lymphocytes (concentration range: 1 LnCap cell per 100 lymphocytes to 1 LnCap cell per 100 million lymphocytes). Cells were detected by anti-PSA (prostate specific antigen) and PAP (prostatic acid phosphatase) antibody by immunochemistry, by fluorescent linked antipancytokeratin antibody by flow cytometry and RT-PCR PSA.. The limit of detection was 1 LnCap cell per 200,000 lymphocytes (1/2.10(5)) for immunochemistry, 1 LnCap cell per 1,000 lymphocytes (1/1.10(3)) for flow cytometry and 1 LnCap cell per 10 million lymphocytes (1/10(7)) for RT-PCR PSA.. RT-PCR, due to its most perceptible limit of detection, appears to be the method of choice for the detection of prostatic epithelial cells. Immunocytochemistry has the advantage of providing a quantitative approach. Flow cytometry is limited by the limit of detection of the apparatus used. The prognostic significance of detection of circulating prostate cancer cells remains to be clarified, but the detection of these cells and their correlation with the primary tumour will provide a better understanding of metastatic phenomena.

Topics: Acid Phosphatase; Evaluation Studies as Topic; Flow Cytometry; Humans; Immunohistochemistry; Male; Neoplastic Cells, Circulating; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Reverse Transcriptase Polymerase Chain Reaction; Tumor Cells, Cultured

Serum concentrations of luteinizing hormone (LH), testosterone, prostatic acid phosphatase (PAP) and prostatic specific antigen (PSA) were measured in 16 patients with advanced prostatic cancer before and after treatment with luteinizing hormone-releasing hormone (LHRH) analogue. An initial rise of serum LH and testosterone levels was observed on day 2 of the treatment. Subsequently, serum concentrations of PAP and PSA showed a transient increase on day 5 of the treatment. This indicates that LHRH analogues had better be given in combination with antiandrogens in patients with metastatic carcinoma of the prostate.

Topics: Acid Phosphatase; Aged; Antineoplastic Agents, Hormonal; Biomarkers, Tumor; Bone Neoplasms; Carcinoma; Follow-Up Studies; Humans; Immunoenzyme Techniques; Injections, Subcutaneous; Leuprolide; Luteinizing Hormone; Male; Prostate-Specific Antigen; Prostatic Neoplasms; Radioimmunoassay; Testosterone; Treatment Outcome

Primary prostatic duct adenocarcinoma, initially labeled as endometrioid carcinoma of the prostate, is a rare neoplasm that displays exophytic growth into the prostatic urethra with involvement of prostatic ducts. Because this tumour arises from preexisting epithelia, there is a possibility that a remnant basal epithelium may be seen in association with these tumours. If this hypothesis is correct, then prostatic duct adenocarcinoma may possibly be mistaken for high-grade prostatic intraepithelial neoplasia (PIN) on needle biopsies. The distribution of basal cells in this tumour has not been described previously. Nine cases of prostatic duct adenocarcinoma and prostatic adenocarcinoma with focal ductal differentiation were studied immunohistochemically with antibodies specifying cytokeratin 34 beta E12, prostate-specific antigen (PSA), and prostatic acid phosphatase (PAP). All cases were positive for PSA and PAP. In some areas of the tumour in eight cases there was a continuous and discontinuous layer of basal cells surrounding islands of carcinoma. This was found with cribriform, comedo, solid, and papillary components of ductal type adenocarcinoma. It is necessary to be aware of the presence of basal cells in association with primary prostatic duct adenocarcinoma. Differentiation of high-grade PIN from this lesion should depend on complex architectural characteristics and Cytologic features rather than presence of a basal cell layer. This finding confirms that the solid, cribriform, papillary, and comedo components initially grow intraluminally within ducts before invasion into surrounding stroma occurs.

Topics: Acid Phosphatase; Adenocarcinoma; Aged; Aged, 80 and over; Carcinoma, Endometrioid; Epithelium; Humans; Keratins; Male; Middle Aged; Prostate-Specific Antigen; Prostatic Neoplasms

Our knowledge about the nature and biological activity of tumor cells residing in the prostate gland after radical radiotherapy (RRT) is limited.. In the present study, residual tumor in core biopsies taken from 37 patients after an average of 6.8 years follow-up after radiation, were investigated with immunohistochemistry for the biochemical markers prostate-specific antigen (PSA), prostatic acid phosphatase (PAP), and the epithelial marker, cytokeratin 8 (CK8).. Tumor cells were cytokeratin-positive in 33 of 34 evaluable specimens (97%). PSA and PAP were expressed in the tumor cells in 94% (34/36) and 81% (30/37) of cases, respectively. No significant correlation was observed between PSA/PAP expression and tumor grade after treatment. Endocrine treatment administered in addition to RRT in 12 of the 37 patients did not affect the expression of PSA or PAP. The expression of both biochemical markers was reduced after radiotherapy in 10 of the 12 cases for which pre- and post-treatment specimens were available.. Tumor cells retain their epithelial characteristics immunohistochemically after radiation, though their morphology sometimes suggests an altered phenotype after treatment. PSA and PAP reactivity was demonstrated in tumor cells nearly 7 years after radiotherapy, which indicates that these cells maintain their biochemical integrity and protein synthesis to a certain extent. Furthermore, endocrine treatment did not abolish PSA or PAP expression in the tumor cells. Whether PSA and PAP immunoexpression provides independent prognostic information needs to be further investigated.

Topics: Acid Phosphatase; Adenocarcinoma; Humans; Immunohistochemistry; Keratins; Male; Neoplasm, Residual; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms

Activin A, a homodimer of the betaA subunit of inhibin, is a member of the TGF-beta family. It is a multifunctional molecule regulating the growth, differentiation, and survival of a variety of cells. Treatment with activin A to an androgen-sensitive human prostatic cancer cell line LNCaP resulted in growth and morphological change and those were accompanied by up-regulation of prostatic differentiation markers prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP). In addition, the expression of androgen receptor was also enhanced by activin treatment. These results suggest that activin has significant influence on LNCaP cells.

Topics: Acid Phosphatase; Activins; Androgens; Biomarkers, Tumor; Cell Differentiation; Cell Division; Humans; Inhibins; Male; Neoplasms, Hormone-Dependent; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Receptors, Androgen; Recombinant Proteins

Eleven hundred and seven patients referred for urological evaluation including measurement of serumprostate specific antigen (PSA) measurement are reviewed. Prostate cancer was diagnosed in 105 patients. PSA was found to be superior to prostatic acid phosphatase in the discrimination between prostate cancer and benign prostatic conditions. In 105 patients with newly diagnosed prostate cancer, scintigraphic evidence of osseous metastases was found in thirty-seven. No patients with a serum PSA value less than three times the upper normal limit of the assay had a positive bone scan. Isotope bone scan can be omitted in these patients, if they are not considered candidates for curative treatment.

Topics: Acid Phosphatase; Adult; Aged; Bone Neoplasms; Humans; Male; Middle Aged; Prostate-Specific Antigen; Prostatic Neoplasms; Radionuclide Imaging; Rectum; Retrospective Studies

We describe the expression of a potentially new tumor marker, human glandular kallikrein 2 (hK2), that may be useful as an adjunct to prostate-specific antigen (PSA) in the diagnosis and monitoring of prostate cancer.. We evaluated 257 radical prostatectomy specimens removed at the Mayo Clinic with pathologic Stage 12 adenocarcinoma to compare the cytoplasmic expression of hK2, PSA, and prostatic acid phosphatase (PAP) in benign tissue, high-grade prostatic intraepithelial neoplasia (PIN), and adenocarcinoma. Two monoclonal antibodies, hK2-A523 and hK2-G586, specific for hK2 were used, as well as antibodies against PSA (PSM-773) and PAP (polyclonal).. Intense epithelial cytoplasmic immunoreactivity was observed in every case for hK2-A523, hK2-G586, PSA, and PAP (100% of cases, respectively). The intensity and extent of hK2 expression for both antibodies were greater in cancer than high-grade PIN; furthermore, high-grade PIN was greater than benign epithelium. Cases of Gleason primary grade 4 and 5 cancer showed hK2 staining in almost every cell, whereas there was greater heterogeneity of staining in lower grades of cancer. In marked contrast to hK2, PSA and PAP immunoreactivity was most intense in benign epithelium and stained to a lesser extent in PIN and carcinoma. The number of immunoreactive cells for hK2 and PSA was not predictive of cancer recurrence.. hK2 was expressed in every cancer, and the expression incrementally increased from benign epithelium to high-grade PIN and adenocarcinoma. PSA and PAP displayed inverse immunoreactivity compared with hK2. The expression of hK2 and PSA was not predictive of cancer recurrence in patients with Stage T2 carcinoma. Expression of hK2 indicates that this kallikrein antigen is both prostate localized and tumor associated. Tissue expression of hK2 appears to be regulated independently of PSA and PAP. Further studies are needed to determine whether tissue immunoreactivity of hK2 will prove clinically useful in the diagnosis and monitoring of prostate cancer.

Topics: Acid Phosphatase; Adenocarcinoma; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Humans; Kallikreins; Male; Middle Aged; Prostate; Prostate-Specific Antigen; Prostatic Intraepithelial Neoplasia; Prostatic Neoplasms

We have compared the steroid regulation of human genes encoding prostatic acid phosphatase (hPAP), prostate-specific antigen (hPSA), and prostate-specific glandular kallikrein (hK2) at the level of transcription. Reporter constructs of hPAP promoter covering the region -734/+467 were functional in both prostatic (LNCaP and PC-3) and nonprostatic (CV-1) cell lines in transient transfections. hPAP -231/+50 with eight identified transcription factor-binding sites showed the highest, and hPAP -734/+467 showed the lowest transcriptional activity in CV-1 cells. The hPAP promoter could not be induced with androgen, glucocorticoid, or progesterone, contrary to the hPSA (-620/+40) and hK2 (-493/+27) promoters in PC-3 cells cotransfected with the respective steroid receptor expression vector. Therefore, steroids cannot directly regulate hPAP gene expression via receptor binding to steroid response elements at -178 and +336, which have been shown to have androgen receptor-binding ability in vitro. Glucocorticoid was the most powerful activator of the hPSA construct at 10-nM steroid concentrations. On the contrary, glucocorticoid stimulation of the transcriptional activity of the hK2 construct was the weakest among the tested steroids. The results indicate that the steroid response elements in the proximal promoters of hPSA and hK2 genes are not androgen specific, offering the molecular basis for the expression of these genes outside the prostate in tissues containing steroid receptors.

Topics: Acid Phosphatase; Androgens; Animals; Cell Line; Chloramphenicol O-Acetyltransferase; DNA Footprinting; Gene Expression Regulation; Glucocorticoids; Haplorhini; Humans; Kallikreins; Male; Progesterone; Promoter Regions, Genetic; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Steroids; Transcription, Genetic; Transfection; Tumor Cells, Cultured

Differences between human prostate carcinoma (PCA, five cases) and benign prostatic hyperplasia (BPH, five cases) in asparagine-linked (Asn) sugar-chain structure of prostatic acid phosphatase (PAP) were investigated using lectin affinity chromatography with concanavalin A (Con A) and wheat germ agglutinin (WGA). PAP activities were significantly decreased in PCA-derived PAP, while no significant differences between the two PAP preparations were observed in the enzymatic properties (Michaelis-Menten value, optimal pH, thermal stability, and inhibition study). In these PAP preparations, all activities were found only in the fractions which bound strongly to the Con A column and were undetectable in the Con A unbound fractions and in the fractions which bound weakly to the Con A column. The relative amounts of PAP which bound strongly to the Con A column but passed through the WGA column, were significantly greater in BPH-derived PAP than in PCA-derived PAP. In contrast, the relative amounts of PAP which bound strongly to the Con A column and bound to the WGA column, were significantly greater in PCA-derived PAP than in BPH-derived PAP. The findings suggest that Asn-linked sugar-chain structures are altered during oncogenesis in human prostate and also suggest that studies of qualitative differences of sugar-chain structures of PAP might lead to a useful diagnostic tool for PCA.

Topics: Acid Phosphatase; Adenocarcinoma; Aged; Chromatography, Affinity; Concanavalin A; Humans; Male; Middle Aged; Prostate; Prostatic Hyperplasia; Prostatic Neoplasms; Wheat Germ Agglutinins

Prostatic acid phosphatase (PAP) is uniquely expressed in prostatic tissue and prostate cancer. In this study, the immunogenicity of PAP was investigated in a male rat model. We show that immunization with recombinant rat or human PAP in CFA leads to a significant Ab response, but does not generate CTL or result in autoimmune prostatitis. In contrast, immunization with recombinant vaccinia expressing human PAP, but not rat PAP, generates a CTL response and tissue-specific prostatitis in the absence of detectable PAP-specific Abs. These findings suggest that a cellular immune response to PAP, rather than Abs, mediates destructive autoimmune prostatitis. Thus, xenogeneic forms of PAP are a new tool for the induction of prostate-specific immunity and may prove useful for the immunotherapy of prostate cancer.

Topics: Acid Phosphatase; Animals; Autoimmune Diseases; Humans; Immunotherapy, Active; Injections, Intravenous; Injections, Subcutaneous; Male; Organ Specificity; Prostate; Prostatic Neoplasms; Prostatitis; Rats; Rats, Inbred Strains; Tumor Cells, Cultured; Vaccines, Synthetic; Vaccinia virus

Although several prognostic factors have been discussed, multivariate analysis that includes tumor marker doubling time has not yet been examined in patients with prostate cancer refractory to endocrine therapy. A number of conventional prognostic factors including doubling times of prostate-specific antigen and/or prostatic acid phosphatase were examined in 56 prostate cancer patients who were refractory to endocrine therapy, using univariate and multivariate analyses. On univariate analysis, 6 parameters (doubling times of prostate-specific antigen and prostatic acid phosphatase at the time of refractory status, performance status, duration from beginning of endocrine therapy to prostate-specific antigen/prostatic acid phosphatase failure, mode of recurrence, the presence or absence of prostate-specific antigen/prostatic acid phosphatase normalization, and alkaline phosphatase) were shown to be significant prognostic factors. On multivariate analysis, only performance status and doubling times of prostate-specific antigen and prostatic acid phosphatase were significant. These observations showed that the doubling times of prostate-specific antigen and prostatic acid phosphatase, calculated at the time of prostate-specific antigen/prostatic acid phosphatase failure by estimating serial prostate-specific antigen or prostatic acid phosphatase, were a valuable prognostic factor in patients with prostate cancer refractory to endocrine therapy.

Topics: Acid Phosphatase; Aged; Aged, 80 and over; Alkaline Phosphatase; Analysis of Variance; Androgen Antagonists; Antineoplastic Agents; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Chlormadinone Acetate; Cisplatin; Disease Progression; Estrogens; Gonadotropin-Releasing Hormone; Humans; Imidazoles; Imidazolidines; Karnofsky Performance Status; Lactates; Male; Middle Aged; Multivariate Analysis; Neoplasm Recurrence, Local; Orchiectomy; Progesterone Congeners; Prognosis; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Retrospective Studies; Survival Rate

The androgen receptor pathway is known to be a key regulator of growth in the normal and pathological prostate. However, the precise mechanisms of this signaling pathway with respect to the different cellular compartments of the prostate remain largely unknown. We have used a primary culture system to grow human prostatic epithelial cells of normal, benign, tumor and metastatic origin, as well as immortalized human prostatic epithelial cell lines, to demonstrate the absence of a direct or indirect effect of androgens on cellular proliferation in vitro. In parallel to this observed androgen independence for growth, all cell systems lost significant expression of androgen receptor, prostate-specific antigen and prostatic acid phosphatase. Since the androgen receptor is expressed in the epithelium in situ, our results suggest that the androgen effect on epithelial cells may be one of prostatic differentiation rather than proliferation, and that the androgen receptor/growth factor pathway acts through mesenchymal-epithelial interactions.

Topics: Acid Phosphatase; Androgens; Cell Differentiation; Cell Division; Cell Line; Cells, Cultured; Dihydrotestosterone; Dose-Response Relationship, Drug; Drug Synergism; Epithelial Cells; ErbB Receptors; Fluorescent Antibody Technique, Indirect; Humans; Immunoblotting; Male; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Receptors, Androgen; Tumor Cells, Cultured

In the present paper, two strains of LNCaP cells derived from the same source (American Type Culture Collection), but studied either at a low passage number (LP) or at a high passage number (HP), were compared in their response to R1881 (a synthetic androgen), all-trans-retinoic acid (atRA), and 1alpha,25-dihydroxycholecalciferol (VD3). [3H]Thymidine incorporation and epidermal growth factor receptor (EGF-R) binding were measured as parameters related to the proliferative response of the cells. The secretion of prostate-specific antigen (PSA) and the mRNA expression of PSA, prostatic acid phosphatase (PAP), and diazepam-binding inhibitor (DBI) were used as parameters reflecting differentiated function. Marked differences were noted in the response of LP and HP cells to androgens. [3H]Thymidine incorporation displayed a bell-shaped dose-response curve in both strains. The amplitude of the response, however, was much higher in HP cells and growth inhibition at high levels of R1881 was only observed in LP cells. On the contrary, androgen induction of PSA secretion and PSA mRNA expression, as well as the expression of PAP was much more pronounced in LP cells, whereas DBI expression was not altered according to passage number. LP cells and HP cells also displayed striking differences in their response to atRA. An up to 6-fold stimulation of [3H]thymidine incorporation was observed in LP cells, whereas in HP cells the only significant effect was growth inhibition. VD3, on the contrary, inhibited [3H]thymidine incorporation to a comparable degree in LP and HP cells. Only marginal effects of atRA and VD3 were observed on PSA secretion. In both LP and HP cells EGF-R levels were increased by androgens and to a slight extent also by atRA and VD3. It is concluded that LP and HP LNCaP cells display markedly divergent responses not only to androgens but also to atRA. The proliferative rather than antiproliferative effects of atRA in some strains of LNCaP should caution against the uncontrolled use of these agents, or of drugs affecting their metabolism, in patients with prostate cancer.

Topics: Acid Phosphatase; Calcitriol; Carrier Proteins; Cell Division; Diazepam Binding Inhibitor; ErbB Receptors; Humans; Male; Metribolone; Neoplasms, Hormone-Dependent; Prostate-Specific Antigen; Prostatic Neoplasms; RNA, Messenger; RNA, Neoplasm; Testosterone Congeners; Thymidine; Tretinoin; Tumor Cells, Cultured

The aim of this study was to investigate the effect of goserelin-acetat (Zoladex) on testosterone suppression, to compare achieved suppression with clinical effects in patients with prostate cancer with bone metastases and consequent painful syndrome, to study the behavior of adiol during treatment and to assess life quality with emphases on the physical and psychological domain in relation to clinical and biological treatment effects. Fifteen patients were treated by Zoladex in one dose every 28 days, and followed-up for 12 months. All patients had several metastatic localizations in the bones, initial high prostate specific antigen (PSA), and high acid (AP) and alkaline phosphatase (ALP). PSA, testosterone, adiol (delta-5-androstenediol), luteinizing hormone (LH), foliculostimulating hormone (FSH), ALP and AP were also measured before every cycle. For evaluation of the life quality Rotterdam Symptom Checklist was used. Clinical progression was not registered during follow-up, with drop of PSA, ALP and AP. Testosterone and adiol displayed mainly inverse trends during treatment. The complete testosterone suppression was never achieved. It seems that Zoladex has quite different influence on LH and FSH, as levels of those hormones have shown opposite trend. Some of the observed hormonal effects could be attributed to stimulation of the monoamine system. Suppression of LH level provoked by administration of LHRH agonists increases level of dopamine in hypothalamus which inhibits releasing of its hormones. By inhibition of corticotropic releasing factor and ACTH, and by its influence on adrenal gland, we could explain drop of adiol levels in the first months of administration of LHRH agonists. Testosterone increase and adiol drop in the first months, and adiol increase following testosterone level drop in the fourth to eight month, may be explained by negative feed back mechanism between different androgens which could be stimulated or provoked by LHRH therapy. The question of effects which are results of LHRH agonists modulation of the monoamine system and consequent activation of other central mechanisms of hormonal regulation is still open. Patients' quality of life under therapy was improved for about 30% in psychological and functional domains. There were no significant changes on physical subscale, during treatment. It seems that the obtained positive psychological treatment effect is not only a consequence of pain decrease, but it could be the result o

Topics: Acid Phosphatase; Adenocarcinoma; Aged; Alkaline Phosphatase; Androstenediol; Antineoplastic Agents, Hormonal; Bone Neoplasms; Gonadotropin-Releasing Hormone; Goserelin; Humans; Male; Middle Aged; Prostatic Neoplasms; Quality of Life; Testosterone

The study was designed to examine the relation of the levels of prostate-specific antigen (PSA), prostatic acid phosphatase (PAP), and alkaline phosphatase (ALP) to clinical stage and bone metastasis in prostate cancer patients.. Serum PSA, PAP, and ALP levels were evaluated in 272 patients with prostate cancer. The relation of the level of PSA, PAP, and ALP to clinical stage and to degree of bone metastasis were examined by a multiple comparison method using ranks. The superiority of a marker in the rate of detection of bone metastasis was evaluated with receiver operating characteristic (ROC) curves. The correlation coefficients of the order of the extent of bone metastasis with PSA, PAP, and ALP were examined with Spearman's rank order correlation coefficient test.. The levels of PSA showed significant differences among 8 pairs of clinical stages. In contrast, the levels of PAP showed significant differences among 6 pairs, and the levels of ALP showed significant differences among only 4 pairs. The area under the ROC curves of PSA, PAP, and ALP for revealing bone metastasis was 84.9%, 81.4%, and 77.3%, respectively. The correlation coefficients of the order of extent of disease (EOD) with log (PSA), log (PAP), and log (ALP) were 0.346, 0.394, and 0.618, respectively, and the levels of ALP showed the most significant differences regarding the extent of bone metastasis.. PSA was the best marker for differentiating clinical stages, but showed limited reliability for stratifying the extent of bone metastasis.

Topics: Acid Phosphatase; Alkaline Phosphatase; Biomarkers, Tumor; Bone Neoplasms; Humans; Male; Neoplasm Staging; Prostate-Specific Antigen; Prostatic Neoplasms; Radioimmunoassay; Reproducibility of Results; Retrospective Studies; ROC Curve

This study was done to review long-term results of radical radiotherapy for prostate cancer.. The records of 674 patients with Stage T1a, T1b, T2a, T2b, T3, and any T,N1,M0 disease, treated with external beam radiotherapy between January 1, 1967 and December 1987, were reviewed. These patients were treated to an average total dose of 66 Gy, with an average fractional dose of 2.05 Gy, using megavoltage. The duration of follow-up for surviving patients ranged from a minimum of 7 years to more than 20 years.. The survival for 151 Stage T1a,T1b patients was 98.5% at 5 years, 93.6% at 10 years, and 75.2% at 15 years. Survival for 346 Stage T2a,b patients was 94.4% at 5 years, 67.9% at 10 years, and 41.5% at 15 years. Survival for 92 Stage T3 patients was 87.3% at 5 years, 54% at 10 years, and 26.6% at 15 years. The survival for 85 any T,N1,M0 patients was 73.9% at 5 years, 34.4% at 10 years, and 8.5% at 15 years. At 15 years, 75.2% of Stage T1a,b patients, 41.5% of Stage T2a,b patients, 21.7% of Stage T3 patients, and 8.5% of Stage T,N1,M0 patients remained free of local recurrence and distant metastases. The elevation of prostatic acid phosphatase prior to radiotherapy was an unfavorable prognostic factor, with impact on both loco-regional recurrences and survival.. The external beam radiotherapy for localized carcinoma of the prostate produced a good loco-regional control, NED, and overall survival. Patients with smaller tumors and low grade fared better than the ones with more aggressive and/or bulky tumors. The weakness of this study is the absence of serial prostate-specific measurements, which were not available during the period under study. The complication rate requiring surgical intervention was low, i.e. 0.4%.

Topics: Acid Phosphatase; Adult; Aged; Aged, 80 and over; Carcinoma; Disease-Free Survival; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Proportional Hazards Models; Prostatic Neoplasms; Radiation Injuries; Radiotherapy Dosage; Time Factors

Clinically benign, whole untrimmed prostates were obtained from 104 patients at autopsy, completely sectioned, and examined microscopically. The histological and gross findings of the prostate were correlated with premortem prostatic acid phosphatase levels (PAP, enzymatic method, ACA, Dupont Co.) to determine how often carcinoma of the prostate (CAP) affected PAP levels and to identify other findings within the prostate associated with elevated PAP levels. Sixty (58%) prostates did not have CAP, 34 (33%) had CAP smaller than 1 ml in volume, and 10 (10%) had CAP larger than 1 ml in volume. PAP levels were elevated (greater than 1 U/L) in 8 of 60 (13%) prostates without CAP, in 2 of the 34 (6%) prostates with CAP smaller than 1 ml, and in 1 of the 10 (10%) prostates with CAP larger than 1 ml. These differences were not statistically significant. Likewise, a statistically significant correlation between PAP levels and patient age, patient race, severe inflammation, of high grade prostatic intraepithelial neoplasia (PIN) was not found. However, there was a statistically significant correlation between PAP levels and prostate weight (p < 0.0001). This study suggest that PAP cannot distinguish between patients with clinically undetected CAP and patients without CAP. Furthermore, elevated PAP levels are often not due to metastatic CAP and additional evidence should be present, even in patients with known CAP, before an elevated PAP level is considered to be conclusive evidence of metastatic CAP.

Topics: Acid Phosphatase; Adult; Aged; Aged, 80 and over; Autopsy; Diagnosis, Differential; Humans; Hyperplasia; Male; Middle Aged; Organ Size; Predictive Value of Tests; Prostate; Prostatic Neoplasms

Approximately 50% of all malignant prostatic tumors contain neuroendocrine cells, which cannot be attributed to small cell prostatic carcinoma or carcinoid-like tumors, and which represent only 1 to 2% of all prostatic malignancies. Only limited data are available concerning the plasma levels of neuroendocrine markers in patients with prostatic tumors. Therefore, we determine the incidence of high plasma levels of neuroendocrine markers in patients with benign and malignant prostatic disease.. The presence of elevated plasma neuropeptide levels was investigated in 135 patients with prostatic carcinoma and 28 with benign prostatic hyperplasia. Plasma chromogranin A, neurone-specific enolase, substance P, calcitonin, somatostatin, neurotensin and bombesin levels were analyzed by immunoassays, and were compared to clinical and pathological stages of disease. Plasma prostatic acid phosphatase and prostate specific antigen levels were also determined. All patients were followed for at least 2 years after inclusion in the study.. Significantly elevated levels of chromogranin A were detected in 15% of patients with prostatic carcinoma before any treatment. During hormone resistant prostate cancer progression plasma chromogranin A and neuron-specific enolase levels were elevated in 55% and 30% of the patients, respectively. In patients with stage D3 disease survival curves were generated by the Kaplan-Meier method, and log rank analysis revealed a statistically significant difference between groups positive and negative for chromogranin A. Substance P and bombesin were also occasionally elevated in prostatic tumors. Determination of neuroendocrine differentiation by neuron-specific enolase or chromogranin A immunoassays was not helpful in the prediction of progressive localized prostatic carcinoma.. Future studies of plasma neuropeptide levels should confirm whether these parameters can be used as prognostic markers during late progression of prostatic carcinoma or for the selection of patients suitable for evaluation of new antineoplastic drugs to be active against neuroendocrine tumors.

Topics: Acid Phosphatase; Aged; Aged, 80 and over; Biomarkers, Tumor; Bombesin; Calcitonin; Chromogranin A; Chromogranins; Humans; Immunoassay; Male; Middle Aged; Neuropeptides; Neurotensin; Phosphopyruvate Hydratase; Prognosis; Prostate-Specific Antigen; Prostatic Hyperplasia; Prostatic Neoplasms; Somatostatin; Substance P; Survival Rate

Phytochromes are ubiquitous red/far-red wavelength-sensitive photoreceptors in plants. Oat phytochrome A is a phosphoprotein. Phytochrome A (phyA) possesses two spatially different sites for phosphorylation with cAMP-dependent protein kinase (PKA) [McMichael & Lagarias (1990) Biochemistry 29, 3872-3878]. To assess the modulation of protein conformation by phosphorylation/dephosphorylation and its possible implication in phytochrome-mediated signal transduction, the conformations of phytochrome have been probed by PKA catalyzed phosphorylation. The phosphorylated species were purified and analyzed, along with untreated phytochrome, by limited proteolysis, circular dichroism (CD) and fluorescence quenching measurements. No significant changes in secondary structure of the phyA molecule after its phosphorylation were observed by CD. However, a subtle topographic and/or electrostatic effect of the phytochrome phosphorylation was detected by the time-resolved fluorescence quenching of Trp residues with Cs+ ions. N-Terminal phosphorylation at Ser17 was unique to the Pr form, but both Pr and Pfr phytochromes were phosphorylated at the hinge region to some extent. Phosphorylation at the hinge region resulted in noticeable changes in the proteolytic patterns, inhibiting cleavage near the phosphorylation site and favoring tryptic digestion of the Lys536-Asn537 peptide bond. Phosphorylation at the N-terminus did not cause observable changes in the helical structure of this region, but had an inhibitory effect on proteinase V8 accessibility at a site near the chromophore attachment. The functional relevance of protein phosphorylation of phyA is also discussed.

Topics: Acid Phosphatase; Adenoma; Adenosine Triphosphate; Amino Acid Sequence; Animals; Avena; Cattle; Circular Dichroism; Cyclic AMP-Dependent Protein Kinases; Humans; Kinetics; Male; Myocardium; Peptide Fragments; Peptide Mapping; Phosphorylation; Phosphoserine; Phosphotyrosine; Phytochrome; Phytochrome A; Prostate; Prostatic Neoplasms; Protein Conformation; Protein Structure, Secondary; Substrate Specificity; Trypsin

In multivariable analysis, post-therapy change in prostate-specific antigen (PSA) was shown to be the most significant factor predictive of survival in patients with androgen-independent prostate cancer. To refine the model, we studied the patterns of change in acid phosphatase, alkaline phosphatase, and lactate dehydrogenase after treatment.. One hundred seven patients with androgen-independent prostate cancer treated on seven different protocols in Memorial Sloan-Kettering Cancer Center were evaluated. For tumor-specific (acid phosphatase and PSA) and nontumor-specific (alkaline phosphatase and lactate dehydrogenase) enzymes, a minimum 50% or 80% decrease from baseline documented on three separate occasions a minimum of 6 weeks apart was required to categorize a patient as having a decline.. Nineteen patients (18%) had either a 50% decline in acid phosphatase or PSA, of whom 13 (68%) had a decline of both markers. Six (32%) patients showed discordance between the two parameters. Declines in PSA level typically preceded declines in acid phosphatase levels. The median survival of patients showing declines in both markers exceeded that of patients showing declines in PSA alone by 1 year. Although baseline measurements of alkaline phosphatase or lactate dehydrogenase did add additional prognostic information, post-therapy changes did not.. Post-therapy declines in PSA and acid phosphatase represent reproducible endpoints for clinical trials in androgen-independent disease. The requirement of a repeated and parallel decline in both markers may improve the results observed by monitoring declines in PSA alone. Monitoring the two parameters may allow the development of models that can be used as surrogate endpoints for response and survival in a disease in which reproducible measurements of response are lacking.

Topics: Acid Phosphatase; Aged; Aged, 80 and over; Alkaline Phosphatase; Follow-Up Studies; Humans; L-Lactate Dehydrogenase; Male; Middle Aged; Proportional Hazards Models; Prostate-Specific Antigen; Prostatic Neoplasms; Survival Analysis

The involvement of vitamin D in prostate carcinogenesis was investigated using the human prostatic LNCaP cells. Incubation of the LNCaP with 100 nM 1 alpha,25-dihydroxyvitamin D3 for 2 days resulted in a 30-40% suppression of cell growth, which was accompanied by a greater than 70% down-regulated expression of the proliferating cell nuclear antigen (PCNA). The intracellular and secreted forms of PSA showed a 2-fold increase following a 48 h culture in the presence of vitamin D3. The vitamin D3-elicited PSA increases were preceded by an induction of androgen receptor (AR) expression, as measured by Western blot analysis and by binding assays using [3H]R1881 as the ligand. These results are consistent with the hypothesis that the growth inhibitory effects of vitamin D3 is partially mediated through its ability to modulate PCNA expression. Moreover, vitamin D3 may effect increases in PSA expression indirectly by up-regulating androgen receptors.

Topics: Acid Phosphatase; Androgens; Calcitriol; Cell Division; Cell Line; Cell Survival; Gene Expression Regulation, Neoplastic; Humans; Kinetics; Male; Metribolone; Proliferating Cell Nuclear Antigen; Prostate-Specific Antigen; Prostatic Neoplasms; Receptors, Androgen; Tumor Cells, Cultured

Human prostatic acid phosphatase (ACPP) and prostate specific antigen (PSA) have been used as diagnostic and prognostic markers of prostate cancer. The structure of ACPP and PSA genes and their encoded proteins are described. The expression of both genes was shown to be elevated significantly in neoplastic tissue when compared to benign prostatic hyperplasia. The prospect of developing new molecular DNA/RNA markers to diagnose prostate cancer is discussed.

Topics: Acid Phosphatase; Antigens, Neoplasm; Base Sequence; Biomarkers, Tumor; Gene Expression; Humans; Male; Molecular Sequence Data; Prognosis; Prostate; Prostate-Specific Antigen; Prostatic Hyperplasia; Prostatic Neoplasms

Human prostatic acid phosphatase (PAcP), a prostate epithelium-specific differentiation antigen, was determined to exhibit the endogenous protein tyrosine phosphatase activity. We investigated the phosphoprotein(s) that might be dephosphorylated by PAcP in human prostate carcinoma cells. Several lines of evidence were presented to show that the tyrosine phosphorylation level of a 185 kDa phosphoprotein (pp185) is negatively correlated with the cellular activity of PAcP. (i) In DU145, PC-3 and high passaged LNCaP prostate carcinoma cells that have no or low PAcP expression, the phosphotyrosine (p-tyr) level of pp185 was higher than that in low passaged LNCaP cells that express an endogenous PAcP. (ii) In LNCaP cells grown in the presence of L(+)-tartrate, an inhibitor of PAcP, the tyrosine phosphorylation of pp185 was increased. (iii) Mediated by Lipofectin, a cationic liposome, the incorporation of purified PAcP protein into DU145 cells resulted in the decreased phosphorylation of pp185. Thus, the results taken collectively demonstrated that the p-tyr level of pp185 is inversely correlated with the cellular activity of PAcP and indicated that the pp185 may be a putative substrate of PAcP in prostate carcinoma cells.

Topics: Acid Phosphatase; Humans; Male; Phosphorylation; Prostatic Neoplasms; Tartrates; Tumor Cells, Cultured; Tyrosine

Sixteen cases of ductal (endometrioid) carcinoma of the prostate are presented. The tumour presents in elderly men (age range 65-87 years) with haematuria or obstructive symptoms. Serum prostate specific antigen may be normal or raised. On cytoscopy, there is often an exophytic lesion in the region of the verumontanum. Histologically, two variants are recognized: papillary and cribriform, of which there were eight cases each. Eight cases consisted of pure ductal carcinoma and seven were mixed, containing a variable proportion of micro-acinar carcinoma. The associated micro-acinar carcinoma had a Gleason score of at least 5. One case of carcinosarcoma with a ductal epithelial component was also included. All cases displayed positive immunohistochemical staining for prostate specific antigen and prostatic acid phosphatase and but were negative for the basal cell marker MA903. The tumour responds well to orthodox micro-acinar carcinoma therapy and appears notably sensitive to hormonal manipulation. Follow-up of the mixed group is restricted to a maximum of 3 years. Of the eight pure cases, five patients are still alive with survival periods of 11, 8, 7, 3 and 1 years. Three patients died of intercurrent disease of which one patient survived 12 years, having received no treatment. This tumour, therefore, can be regarded as having a good prognosis.

Topics: Acid Phosphatase; Aged; Aged, 80 and over; Carcinoma, Endometrioid; Humans; Immunohistochemistry; Male; Prostate-Specific Antigen; Prostatic Neoplasms

Malignant pleural effusions due to prostatic carcinoma are rare. We examined the cytologic and clinical presentations of 14 malignant pleural effusions caused by prostate cancer. These cases represented 2.3% of all positive pleural effusions at our institution. All patients (n = 10) had high grade, high stage tumors, including three with small cell anaplastic carcinoma. Three cases had clinically documented metastases to pleura, and in two cases, metastases were documented at autopsy. Most tumor cells had large nucleoli and were arranged in small, loosely cohesive groups. Fluids due to the small cell type of prostate carcinoma often contained a mixture of cells similar to those seen in small cell carcinoma of other sites such as the lung, as well as cells resembling the more typical type of prostate cancer. Prostatic specific antigen and prostatic acid phosphatase were positive in less than 50% of these malignant effusions. We conclude that prostatic carcinoma in pleural effusions occurs most commonly in high grade, high stage tumors and has a characteristic cytologic appearance. Negative staining for PSA and PAP does not rule out a prostatic source for malignant cells in effusions.

Topics: Acid Phosphatase; Adenocarcinoma; Humans; Male; Pleural Effusion, Malignant; Pleural Neoplasms; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms

To relate findings from a novel approach, ejaculate cytology, to the established reference, histopathology from transrectal ultrasonography (TRUS)-guided prostatic biopsies, in patients at risk of having prostatic cancer on the basis of an abnormal digital rectal examination (DRE) and/or an elevated serum prostate specific antigen (PSA). PATIENTS SUBJECTS AND METHODS: Thirty-seven men suspected of having prostatic carcinoma provided ejaculate specimens which were collected in Hanks solution. The specimens were centrifuged to form a pellet from which smears were made for cytological examination. Immunohistochemical staining for PSA and prostatic acid phosphatase (PAP) were performed on embedded blocks of these cells. TRUS-guided sextant biopsies were performed for histological specimens using standard clinical procedures. A control group of 32 men < 30 years of age, with no family history of prostatic cancer, also produced specimens of ejaculate which were processed similarly.. Frankly malignant and atypical prostatic cells were identified in ejaculate specimens from 14 of the 37 patients. Of 12 patients with TRUS biopsies positive for malignancy, nine (75%) had abnormal cells in their ejaculates. Furthermore, five of 25 patients with negative biopsies for adenocarcinoma also had abnormal ejaculate cytology; two of these five patients had high-grade prostatic intra-epithelial neoplasia (PIN). In the control group, no PSA- or PAP-positive prostatic epithelial cells were identified. Normal prostatic cells were not seen in any of the ejaculate specimens examined.. These results indicate that ejaculate cytology, which is a non-invasive and easily repeated investigation, may prove to be a useful approach in the early detection of cancer of the prostate. However, its value in this role, together with the clinical significance of cytological findings, needs to be established, especially in relation to PSA and TRUS biopsy.

Topics: Acid Phosphatase; Biopsy; Humans; Immunohistochemistry; Male; Prostate-Specific Antigen; Prostatic Neoplasms; Reference Values; Semen; Sensitivity and Specificity

We describe two cases of mucinous adenocarcinomas involving and confined to the prostate and originating from the prostatic urethra. These cases were identical to adenocarcinomas arising within the urinary bladder and differed from mucinous adenocarcinoma of the prostate. In both cases, an in situ adenocarcinoma component was identified in the overlying prostatic urethra. In one case the in situ adenocarcinoma arose in a villous adenoma of the urethra. Both cases contained lakes of mucin lined by tall columnar epithelium with varying degrees of cytologic atypia, and one case had mucin-positive signet cells. In contrast, mucinous adenocarcinomas of the prostate demonstrate tubules and cribriform glands floating within mucin; mucin-positive signet cells are rare. Both tumors were negative immunohistochemically for prostate-specific antigen and prostate-specific acid phosphatase and positive for carcinoembryonic antigen. One case was treated by radical prostatectomy, and the patient was without evidence of disease with short follow-up. Following simple prostatectomy, the other patient did not undergo definitive therapy for several years, at which point the tumor had progressed locally to an advanced stage. In terms of therapy, the distinction between mucinous adenocarcinoma or urinary bladder-type arising in the prostate depicted within the current study and mucinous adenocarcinoma of the prostate is significant.

Topics: Acid Phosphatase; Adenocarcinoma, Mucinous; Aged; Carcinoembryonic Antigen; Diagnosis, Differential; Humans; Immunohistochemistry; Male; Mucins; Prostate-Specific Antigen; Prostatic Neoplasms; Urethral Neoplasms

Analyses of total and prostatic acid phosphatase levels in patients undergoing prostatectomy at Iyi-Enu Hospital, Ogidi, Nigeria between June, 1989 and May, 1992 showed the following: total acid phosphatase sensitivity 72%; specificity 27%; predictive value 28% and while prostatic acid phosphatase sensitivity 72%; specificity 41%; predictive value 50%. While the prostatic acid phosphatase is better than total acid phosphatase both suffer from unacceptably low specificity and high rate of false positives. The clinical value is therefore poor and decision on surgery should be made on other parameter, especially rectal examination.

Topics: Acid Phosphatase; Aged; Aged, 80 and over; Humans; Male; Mass Screening; Middle Aged; Nigeria; Patient Selection; Prospective Studies; Prostatectomy; Prostatic Neoplasms; Reproducibility of Results; Sensitivity and Specificity

The age eligibility for the mass screening (MS) for prostate cancer was investigated.. This study was performed in subjects examined by MS from 1981 to 1994 in Gunma Prefecture, Japan. MS was performed by digital rectal examination (DRE) and prostatic acid phosphatase from 1981 to 1991, and by DRE, transrectal ultrasonography and prostate specific antigen from 1992 to 1994.. It was demonstrated that the prostate cancer detection rate was affected by the ratio of subjects newly and previously examined, the age distribution in the group examined and the diagnostic modality. It was also demonstrated that the detection rate of early stage prostate cancer was also affected by the age distribution and the diagnostic modality. The effective detection rate was determined on the assumption that the purpose of MS is the detection of the subjects who have the indication for the radical prostatectomy, and the effective detection rate was calculated in the range from 50 to 69 years for age eligibility, and B and C for clinical stage. It was estimated that effective detection rate was 0.37 to 0.61%. They were higher than the detection rate of MS for other organ cancers.. The eligibility is 50 to 69 years. If subjects in the range of 70 to 74 are included in this project, it is necessary to make an effort practice a subject-education about the prostate cancer natural history and the radical prostatectomy indication.

Topics: Acid Phosphatase; Age Factors; Aged; Aged, 80 and over; Humans; Male; Mass Screening; Middle Aged; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Ultrasonography

The number of cases of prostate carcinoma (PCA) is steadily inceasing in Japan. The clinical application of a reliable tumor marker, prostate specific antigen (PSA) for the diagnosis, as well as the increasing elderly population in Japan may account for this increase. The subjects were patients at the Nara Medical University and its affiliated hospitals; 1) 687 cases without PCA were evaluated for age-specific PSA and the incidence of abnormal PSA following urological manipulations, 2) 135 cases with histological proven BPH by transurethral resection of prostate (TUR-P) were examined for PSA density (PSAD) and positive PSA rate in BPH, 3) 135 cases receiving a needle biopsy with suspicion of PCA were examined for the efficacy of PSA and PSAD and other parameters, and 4) 459 PCA cases treated between 1988 and 1994, were examined for specific PSA and PSAD values by stage and degree of cell differentiation. The PSA assay used in this study was MARKIT-M PA (normal range < or = 3.6 ng/ml). The PSA was decreased gradually with age in non-PCA patients, and abnormal PSA was found in 5.5% of these patients following manipulations. The average PSA was 2.95 +/- 2.03 ng/ml in 130 BPH patients (mean age: 71.1 +/- 7.0 years old. and average prostate volume: 32.9 +/- 16.1 ml). And abnormal PSA level (more than 3.61 ng/ml) was found in 22.3%. The mean PSAD was 0.1.0 +/- 0.06, and PSAD was below 0.15 in 86.1% of these BPH cases. Among the 135 cases receiving a needle biopsy, 33 cases had PSA values between 3.61 and 10.0 ng/ml. Of these cases, PCA was found in 18.5% of the 27 cases with a PSAD below 1.5, and in 33.3% of the 6 cases with a PSAD over 1.5. PSA and PSAD were proportionally increased with stage, and a significant difference in the PSA value was observed between stage B1 and B2, and stage C and D (P < 0.05). However, PSA and PSAD values were not significantly correlated with the cell differentiation in PCA stage A2-C. In total, PSA was 18.1 ng/ml in well, 23.9 ng/ml in moderately and 35.9 ng/ml in poorly differentiated type PCA. The positive rate of PSA was 22.3, 65.4 and 83.5%, that of prostate acid phosphatase (PAP) was 10.0, 17.8 and 45.8%, and that of GSM was 25.0, 14.7 and 68.4%, in BPH, stage A PCA and stage BPCA, respectively. In conclusion, PSA is the most reliable tool in the diagnosis of localized PCA. However, the differential diagnosis of BPH and localized PCA is difficult when the PSA value is between 3.61 and 10.0 ng/ml, and accurate staging of loc

Topics: Acid Phosphatase; Adenocarcinoma; Adult; Aged; Biomarkers, Tumor; Biopsy, Needle; Humans; Male; Middle Aged; Neoplasm Staging; Predictive Value of Tests; Prostate; Prostate-Specific Antigen; Prostatic Hyperplasia; Prostatic Neoplasms; Sensitivity and Specificity

Prostatic carcinoma has proven extremely difficult to establish as cell lines or xenografts. In this article, we describe a new series of prostate cancer xenografts propagated in athymic mice, designated LuCaP 23, developed from prostate metastases harvested at autopsy shortly after death. Tumor from three separate metastatic deposits was developed into three xenograft sublines: two from lymph node metastases (LuCaP 23.1 and 23.8) and one from a liver metastasis (LuCaP 23.12). Fluorescence in situ hybridization analysis confirms the xenografts are human. Histologically, the xenografts are comprised of columnar epithelial cells arranged in a glandular pattern. Tumor doubling times range from 11 to 21 days for the three sublines. The cells secrete large amounts of prostate-specific antigen (PSA) with PSA indices of 1.27, 1.63, and 5.21 ng/ml/mm3 for the mice bearing the LuCaP 23.1, 23.8, and 23.12 sublines, respectively. Following androgen deprivation a temporary decrease in PSA secretion and a decrease in tumor size are noted in most tumors. Eventually, the tumors become androgen independent and resume growth in castrate hosts. The degree of PSA response to castration and time to PSA nadir correlate with time to progression. Thus, unlike most existing models of prostatic carcinoma, this novel xenograft exhibits many phenotypic characteristics of clinical prostatic carcinoma, including androgen sensitivity. These properties make this xenograft an excellent model for future study.

Topics: Acid Phosphatase; Animals; Chromosome Aberrations; Humans; Male; Mice; Mice, Inbred BALB C; Middle Aged; Neoplasm Transplantation; Orchiectomy; Prostate-Specific Antigen; Prostatic Neoplasms; Transplantation, Heterologous

Clinical and immunohistochemical studies were conducted to evaluate prostatic papillary adenocarcinoma and prostatic papillary hyperplasia. Subjects consisted of 5 cases of papillary adenocarcinoma and 2 cases of papillary hyperplasia. There is no conclusive clinical factor for preoperative diagnosis, but we attach importance to endoscopic findings. PSA, PAP, high molecular weight cytokeratin, and PCNA were evaluated immunohistochemically. PSA became positive in every instance but one--a case of papillary adenocarcinoma which became +/-. PAP was + in all cases, except for 1 case of papillary adenocarcinoma. Basal cells were positive for high molecular weight cytokeratin in 2 cases of papillary hyperplasia but were missing in papillary adenocarcinoma. Although PCNA was free from positive nuclei in papillary hyperplasia, positive nuclei were found in all cases of papillary adenocarcinoma. Considering these immunohistochemical results, papillary adenocarcinoma can be said to originate in the glandular epithelium of the prostate, as does ordinary prostatic carcinoma.

Topics: Acid Phosphatase; Adenocarcinoma, Papillary; Aged; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Proliferating Cell Nuclear Antigen; Prostate-Specific Antigen; Prostatic Neoplasms

This study evaluated the growth of human prostate tumors in histoculture, an in vitro culture technique that maintains three-dimensional tissue structure and organization. Eighty-six percent of 50 tumor specimens from 50 patients were successfully cultured. The histocultures showed proliferation of epithelial tumor cells and stromal cells. Prostate specific antigen (PSA) and prostatic acid phosphatase (PAP) were detectable by immunohistochemistry for at least 8 weeks. Synthesis of PSA was further confirmed by its presence in medium. The mean thymidine labeling index (LI) of the neoplastic cells was 62%. There was no correlation between thymidine LI and tumor grade. The explants maintained their characteristics for at least 8 weeks as indicated by unchanged thymidine LI, PSA and PAP immunohistochemistry after 2 and 8 weeks in culture. A 24 to 48 hour delay in processing the tissues for culture did not reduce the thymidine LI. The thymidine LI and PSA and PAP staining in tumors cultured in a Minimal Essential Medium (MEM)-based or a PFMR-4-based culture medium were similar, suggesting an insignificant effect of the medium on cell proliferation. Migration of neoplastic cells from the tissue fragments into the collagen gel matrix was noted in 1 of 10 samples cultured in MEM-based medium versus 8 of 10 samples cultured in PFMR-4 medium (p < 0.01). Exposure of 13 patient tumors to suramin, doxorubicin and 5-fluorouracil at clinically relevant concentrations and duration showed tumor sensitivity in 23%, 31% and 15% of the specimens. These values approximate the historical clinical response rates. These data suggest that the histoculture system holds promise for short-term culture of human patient prostate tumor specimens for biologic and pharmacologic studies.

Topics: Acid Phosphatase; Cell Division; Culture Techniques; Drug Screening Assays, Antitumor; Humans; Immunohistochemistry; Male; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Thymidine

To compare the relative sensitivity and specificity of prostate-specific antigen (PSA) as a test for prostate cancer over a range of PSA values in a variety of patient groups, and to compare the sensitivity and specificity of PSA and prostatic acid phosphatase (PAP).. Receiver operating characteristic (ROC) curves (sensitivity plotted against 1-specificity) were constructed to compare the ability of PSA to discriminate men with prostate cancer (n = 257) from those with benign prostatic hyperplasia (BPH) (n = 220) or control patients (n = 164). Receiver operating characteristic curves were also constructed to compare PSA and PAP in 173 men with either BPH or prostate cancer.. When patients with symptomatic BPH and those with advanced prostate cancer are excluded, a PSA of 8 ng/mL has a sensitivity of 94% and a specificity of 98% for prostate cancer. In patients presenting with symptoms suggestive of bladder outflow obstruction, PSA remains a sensitive marker for prostate cancer (93% sensitivity at 10 ng/mL) but its specificity (65%) is poor. PSA is a sensitive test for skeletal metastases but levels of 60-80 ng/mL are required to achieve a specificity of 70% or more. The sensitivity of PSA is far superior to that of PAP.. Serum PSA provides good discrimination between patients with and without prostate cancer. The sensitivity and specificity of PSA can be improved by excluding men with symptomatic BPH. The specificity of PSA as a diagnostic test for prostate cancer is reduced in men with symptoms of bladder outflow obstruction. For reasonable sensitivity and specificity, a PSA of 60-80 ng/mL is required for differentiating non-metastatic from metastatic prostate cancer. The ROC curve comparing PSA and PAP provides a graphical demonstration of the superiority of PSA as a tumour marker. The ability of PSA to identify prostate cancer can be improved by selecting out groups of patients and by adjusting the cut-off level of PSA to the population under study.

Topics: Acid Phosphatase; Biomarkers; Bone Neoplasms; Humans; Male; Prostate-Specific Antigen; Prostatic Hyperplasia; Prostatic Neoplasms; Sensitivity and Specificity; Urinary Bladder Diseases; Urinary Retention

The annual incidence of carcinoma of the prostate gland increased from an estimated 76,000 cases in 1984 to 200,000 in 1994. Part of this increase may be the result of increased detection. Management of the disease has also changed. To measure such changes, the American College of Surgeons conducted a patient care evaluation study of carcinoma of the prostate gland.. Information was voluntarily submitted by cancer registrars on forms designed by a team of specialists. Data were received from 730 hospitals (of 2,000 hospitals invited for the study) on 14,716 patients with newly diagnosed adenocarcinomas of the prostate gland in 1984 and from 1,035 hospitals for 23,214 patients with carcinoma of the prostate gland in 1990.. From 1984 to 1990, there was increased diagnostic use of the prostate specific antigen (PSA) test (from 5.1 to 66.4 percent of incident carcinomas) and transrectal ultrasound (TRUS) (0.9 to 19.7 percent). Use of the prostatic acid phosphatase assay declined from 62.4 to 47 percent. Although the proportion of early stage (0, I, II) disease increased for all racial or ethnic groups combined, the greatest increase was for whites (from 57.3 to 60.6 percent), while the increase for African-Americans was less (from 46.9 to 48.3 percent). The use of radical prostatectomy without radiation therapy or chemotherapy increased from 7.3 to 20.3 percent and the proportion of patients receiving no carcinoma-directed treatment decreased from 37.8 to 30 percent. Radiation therapy remained the same. Hormone therapy without radical prostatectomy declined from 24.4 to 19.7 percent. African-Americans had a lower five-year survival rate than whites, even when stratified for stage.. The diagnostic use of the PSA test and TRUS increased markedly by 1990 and may have contributed to the increased diagnosis of carcinomas of the prostate gland and the earlier stage at diagnosis. The overall use of radical prostatectomy has increased and the proportion of patients receiving no treatment has decreased. African-Americans had a lower five-year survival rate than other groups, even when stage was controlled.

Topics: Acid Phosphatase; Adenocarcinoma; Aged; Aged, 80 and over; Biopsy; Combined Modality Therapy; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Prostate-Specific Antigen; Prostatectomy; Prostatic Neoplasms; Racial Groups; Radiotherapy Dosage; Registries; Survival Rate; Tomography, X-Ray Computed; Ultrasonography

Recent reports suggest that radionuclide bone scan (BS) may not be necessary in the standard staging evaluation of patients with prostate cancer when serum prostate-specific antigen (PSA) levels are normal. To evaluate the ability of PSA to predict BS findings, we retrospectively reviewed the case records of 118 consecutive patients (median age 73 years, range 50-90 years) with newly diagnosed, untreated, pathologically proven prostate cancer who underwent BS and serum PSA sampling within a period of no more than 3 months. Fifty-four out of 118 BSs demonstrated metastatic bone disease. A PSA value of less than 10 ng/ml excluded bone metastasis; of 35 patients with a serum PSA level of 20 ng/ml or less, seven had a positive BS (negative predictive value of 80%). These findings provide additional confirmation of the value of low serum PSA concentrations in excluding the need for a staging BS, although the threshold for a high value of negative predictive accuracy is lower than previously reported.

Topics: Acid Phosphatase; Adenocarcinoma; Aged; Aged, 80 and over; Biopsy; Bone and Bones; Bone Neoplasms; Humans; Male; Middle Aged; Predictive Value of Tests; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Radionuclide Imaging; Retrospective Studies; ROC Curve

The usefulness of estramustine phosphate (ECT) for preventing flare-up in goserelin acetate depot therapy for advanced prostate cancer was studied. Pretreatment with ECT 560 mg daily for 3 weeks almost completely prevented the rise in testosterone level seen in goserelin acetate depot therapy and no signs or symptoms of tumor flare were observed. Long-term ECT completely blocked the rise in luteinizing hormone and testosterone level, but ECT at this dosage was likely to cause complications. The administration of ECT 560 mg daily for 3 weeks prior to goserelin acetate depot therapy was considered sufficient to prevent tumor flare, and its effect was considered to be more marked than that of short-term treatment with antiandrogens.

Topics: Acid Phosphatase; Aged; Aged, 80 and over; Carcinoma; Disease Progression; Drug Therapy, Combination; Estramustine; Goserelin; Humans; Injections, Subcutaneous; Luteinizing Hormone; Male; Middle Aged; Prostate-Specific Antigen; Prostatic Neoplasms; Testosterone

To estimate the growth rate of prostate cancer, the doubling times of prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP) were determined in 51 patients: 44 were refractory to endocrine therapy, and 7 were in an untreated state. Since an exponential increase in PSA and PAP was observed in all patients, the doubling time was calculated from a semilogarithmic plot of the respective markers. PSA doubling time was almost identical with that of PAP. The tumor marker doubling time in untreated patients was approximately 10 times greater than that in the patients who were refractory to endocrine therapy. In endocrine refractory patients, the tumor marker doubling time in patients who showed deterioration of bone lesions was less than that in patients with local regrowth and/or lymph node metastasis. The prognosis of endocrine refractory patients from the time showing tumor marker failure was examined. The group showing the longest time (> 80 days) had better prognosis than that shown by the other groups with shorter doubling times. It is concluded that the determination of tumor marker doubling time is of value for measuring the growth rates of prostate cancer, and for assessing prognosis after relapse.

Topics: Acid Phosphatase; Aged; Aged, 80 and over; Biomarkers, Tumor; Disease Progression; Hormones; Humans; Male; Middle Aged; Prognosis; Prostate-Specific Antigen; Prostatic Neoplasms; Radioimmunoassay; Retrospective Studies

The study of stromal-epithelial interactions greatly depends on the ability to culture both cell types separately, in order to permit analysis of their interactions under defined conditions in reconstitution experiments. Here we report the establishment of explant cultures of human prostatic stromal cells and their immunocytochemical characterization. As determined by antibodies to keratin and prostate specific acid phosphatase, only small numbers (< 5%) of epithelial cells were present in primary cultures; subsequent passaging further reduced epithelial cell contamination. Antibodies against intermediate filament proteins (keratins, vimentin, and desmin) and smooth muscle actin microfilaments demonstrated that stromal cells from benign prostatic hyperplasia and prostate carcinoma differed in regard to their differentiation markers. Two contrasting phenotypes were identified in cultures derived from these two different lesions: One exhibiting fibroblastic features, was predominant in cultures derived from benign lesions and a second, showing varying degrees of smooth muscle differentiation, was more abundant in carcinoma-derived cultures. These findings are indicative of a remarkable divergence in the stromal-epithelial relationships associated with these pathological conditions and may provide us with a potential tool for studying these processes.

Topics: Acid Phosphatase; Actins; Biomarkers; Desmin; Humans; Immunohistochemistry; Keratins; Male; Prostate; Prostatic Hyperplasia; Prostatic Neoplasms; Receptors, Androgen; Tumor Cells, Cultured; Vimentin

Clinical and pathologic characteristics of stage T1c disease (nonpalpable and nonvisible cancer) was studied retrospectively in men who underwent radical prostatectomy in order to better understand this disease entity. Findings in stage T1c disease (16 patients) were directly compared with those in stage T2b disease (11 patients). No significant difference was observed between these groups with regard to age, preoperative serum prostatic acid phosphatase level, prostatic weight, numbers of tumor foci, total tumor volume, volume of index cancer and tumor grade (p > 0.05). Preoperative prostate specific antigen concentration was significantly lower in stage T1c group (p < 0.05). Substantially larger number of patients with stage T1c disease had pathologically organ confined disease when compared with T2b group (86.7% versus 45.5%, p < 0.05). Seventy-five percent (12/16) of stage T1c and 90.9% (10/11) of stage T2b disease were considered clinically significant. Most of stage T1c disease is organ confined and clinically significant. Clinical and pathologic features of these tumors are similar to those in T2b disease. Twenty-five percent of stage T1c disease, however, are small and thus may potentially be overtreated. Enhanced detection of prostate cancer achieved with modern technology can lead to undesirable treatment of clinically insignificant tumors. Preoperative diagnostic modalities which can reliably distinguish groups of tumor with different biological potential are needed to overcome this contradiction.

Topics: Acid Phosphatase; Aged; Biopsy; Humans; Male; Middle Aged; Neoplasm Invasiveness; Neoplasm Staging; Palpation; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Retrospective Studies

The aim of the present investigation was the evaluation of cost-effectiveness of variables used in monitoring patients with inoperable prostate cancer. Prostate-specific antigen (PSA), prostatic acid phosphatase (PAP), and radionuclide bone scan were considered. The tumor marker positivity was assessed according to dynamic criteria (> 50% increase between consecutive samples). 108 patients entered the study; 72 patients treated with a luteinizing hormone-releasing hormone analogue were followed up for periods ranging from 12 to 64 months. PSA and PAP levels were measured using immunometric assays. Both cutoff-based and dynamic, serial sample-based decision criteria were employed. With respect to a positive bone scan, PSA showed negative predictive values of 82 and 77%, respectively, using 4 and 10 ng/ml as cutoff points. Progression of the disease to the bone occurred in 20 patients: in 17 PSA was the first indicator of progression, in the other 3 PAP anticipated PSA for a very short time (3-4 months), which was not of relevance to clinical decisions. PAP is less specific and sensitive than PSA; PAP may eventually provide information on disease status in a limited percentage of patients with advanced prostate cancer treated with androgen ablation, being differently regulated with respect to PSA. No increasing PSA profile was detected in patients who responded to the therapy. From the results of the present investigation, we draw the following conclusions: (1) PSA can be used reliably as a unique tool in the follow-up of patients for the early detection of progressive disease, and (2) dynamic criteria of evaluation of serial PSA determinations probably provide more effective and earlier clinical information.

Topics: Acid Phosphatase; Aged; Aged, 80 and over; Biomarkers, Tumor; Bone and Bones; Bone Neoplasms; Cost-Benefit Analysis; Follow-Up Studies; Gonadotropin-Releasing Hormone; Humans; Immunoradiometric Assay; Male; Middle Aged; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Radionuclide Imaging; Retrospective Studies; Tomography, X-Ray Computed

Bone metastases frequently occur in prostate carcinoma. Total body radionuclide scan with diphosphonate methylene labelled with 99Tc is commonly used to diagnose such metastases. However this technique is aspecific and frequently unreliable. In recent years several biological markers dealing with bone metabolism were studied. Serum determination of skeletal alkaline phosphatase (ALP) and moreover of its bone isoenzyme (BAP) could be considered a reliable index of osteoblastic activity. In this preliminary report we analyzed a group of 43 patients affected by prostate carcinoma with or without bone metastases. The American Urological Association (AUA) staging system was adopted. Sixteen patients were D2, bone metastases had been suspected by means of radionuclide bone scan and confirmed by Computerized Tomography and/or aimed X-rays. Tandem R-Ostase by Hybritech was used to measure BAP, normal value is set to 20 micrograms/L. All D2 tumours had pathological BAP values (mean value 87.50 micrograms/l); 1/3 stage A, 5/13 stage B, 5/9 stage C and 0/2 stage D1 patients had pathological findings. One of this patients, stage C, revealed a bone metastase at a later bone scan.

Topics: Acid Phosphatase; Alkaline Phosphatase; Biomarkers, Tumor; Bone Neoplasms; Carcinoma; Humans; Isoenzymes; Male; Neoplasm Proteins; Neoplasm Staging; Osteoblasts; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Radionuclide Imaging

We have previously shown that the intensity (graded semiquantitatively as 1-4+) of tissue prostate-specific acid phosphatase (PSAP) staining determined immunocytochemically in a cohort of prostate carcinoma patients from Radiation Therapy Oncology Group Protocols (RTOG) protocols 75-06 and 77-06 correlated with survival. The extent of this staining was heterogeneous and was estimated. The extent of staining was not found to be significantly associated with survival. We undertook the present quantitative study to see if the improved precision and reliability of measurement of the intensity and extent of prostate specific acid phosphatase staining would confirm and extend our previous observations.. Patient cohorts representative of the entire group were obtained from RTOG 75-06 plus 77-06 and 83-07. The RTOG 77-06 plus 75-06 patients (No-Hormone population) did not receive preradiation hormonal therapy. RTOG 83-07 patients (Prehormone population) received one of two types of preradiation chemical androgen ablation. In this study, histologic slides of tumors were immunocytochemically stained for PSAP by the peroxidase-antiperoxidase (PAP) technique using diaminobenezidene (DAB) as a substrate and hematoxylin as a nuclear counterstain. The intensity and extent of immunocytochemical PSAP staining (IPSAP stain) was quantified using our dual wavelength and batch mode image process technique.. Our study of 151 cases confirmed that overall survival of patients in both populations was positively correlated with the intensity and extent of IPSAP stain. Results of the two studies were similar. The statistical significance of the relationship of both extent and intensity was greater in the cohort from protocol 83-07, which was the patient group receiving pretreatment with hormones. In a Cox multiple regression analysis including clinical stage, Gleason and M. D. Anderson grades, and the cohort of patients (Prehormone or No-Hormone group) as covariables, both the intensity and extent of the IPSAP stain significantly correlated with survival along with M. D. Anderson grade of the tumor.. Quantitative image analysis of the IPSAP stain predicts survival in patients treated with external beam radiotherapy with and without prior hormonal therapy.

Topics: Acid Phosphatase; Humans; Isoenzymes; Male; Multivariate Analysis; Neoplasm Staging; Prostatic Neoplasms; Survival Analysis

Patients with regionally localized hormone refractory adenocarcinoma of the prostate are often referred for radiotherapy to relieve local symptoms, prevent further local progression, or prevent impending urinary tract obstruction. However, the merits of radiotherapy for this patient population have not been documented. In this retrospective series, the results of 29 such patients treated at our institution between 1987-1992 are reviewed.. Prior to androgen ablation, the majority of these patients (79%) had Stage D0 or D1 disease. After androgen ablation, radiotherapy was given to 16 (55%) for progressive symptoms (mostly urinary obstructive), 11 (38%) for palpable local progression in the absence of symptoms, and 2 for a rising prostate specific antigen (PSA) profile without palpable disease. None of the patients had distant metastasis at the time of radiotherapy. The median dose to the prostate was 66 Gy and the median follow-up after radiotherapy was 43 months.. Following local-regional radiotherapy, the actuarial rate of local failure at 4 years was only 39%. However, 80% had disease progression or a rising PSA in this time period. The actuarial survival at 4 years following radiotherapy was 39%. Univariate analyses of potential prognostic factors revealed that preandrogen ablation Gleason score, preradiotherapy PSA, and preradiotherapy prostatic acid phosphatase (PAP) were predictive of patient outcome. Most importantly, doses above 60 Gy to the prostate at standard fractionation were associated with symptom-free local control in 90% of patients at 3 years. The majority of the patients were treated using limited fields (n = 20).. The regionally localized hormone refractory prostate cancer patients described benefited from high dose, continuous course, local radiotherapy in that excellent local control rates were obtained for an extended period. Because the majority of these patients fail with distant metastasis within 4 years, this treatment represents an aggressive approach to palliation that is justified by the maintenance of freedom from local symptoms.

Topics: Acid Phosphatase; Adenocarcinoma; Adult; Aged; Biomarkers, Tumor; Disease Progression; Follow-Up Studies; Humans; Male; Middle Aged; Orchiectomy; Prostate-Specific Antigen; Prostatic Neoplasms; Radiotherapy Dosage; Retrospective Studies; Survival Analysis; Treatment Failure

We report a total of 169 serial bone scan studies conducted in 21 patients with histologically proven metastatic cancer of the prostate. Aim of the study was to investigate the concordance of findings on bone scans with serum acid phosphate (AP) levels and the clinical performance status (CPS) of the patients, and to see how important bone scan is by itself in determining the metastatic progression in the follow-up. Eighty-seven and 86% of scans demonstrated changes concordant with AP and CPS levels subsequently. It was also found that 100% of the progressions on bone scans along with elevated levels of AP had been confirmed as metastatic progression, whereas only 41% of progressions on bone scans solely had been shown to be metastases in the follow-up investigations. Findings on bone scans not in correlation with clinical findings and serum AP levels are mostly misleading. Use of bone scans in conjunction with serum AP levels and most probably with prostate-specific antigen and CPS is the most reliable and therefore treatment modality changes should not be based on bone scans only.

Topics: Acid Phosphatase; Adenocarcinoma; Bone and Bones; Bone Neoplasms; Clinical Enzyme Tests; Follow-Up Studies; Humans; Karnofsky Performance Status; Male; Middle Aged; Prostatic Neoplasms; Radionuclide Imaging; Retrospective Studies; Sensitivity and Specificity; Technetium Tc 99m Medronate; Time Factors

We investigated the effects of inositol hexaphosphate (InsP6) on growth inhibition and differentiation of human prostate cancer cells PC-3 in vitro. A significant dose- and time-dependent growth inhibition was observed as tested by the MTT-incorporation assay (P < 0.05 at 1 mM InsP6 after 24 h treatment, P < 0.01 at 0.1 mM after 3 days). DNA synthesis as determined by [3H]thymidine incorporation assay was also suppressed by InsP6 in a dose-dependent manner, occurring as early as 3 h after treatment and continuing up to 48 h (P < 0.01 at 1 mM InsP6). A 9- to 10-fold increase (P < 0.01) in expression of HLA class I molecule associated with tumor immunosurveillance and cell differentiation was induced by InsP6. The marker for prostatic cell differentiation, prostate acid phosphatase, was significantly (P < 0.05) increased after 48 h treatment at 0.5-5 mM InsP6. Since InsP6 strongly inhibits growth and induces differentiation in human prostate cancer cells in vitro, in vivo studies using a tumor xenograft model and a prostate carcinogenesis model are warranted to validate the efficacy of InsP6 in the treatment and prevention of prostate cancer.

Topics: Acid Phosphatase; Cell Differentiation; Cell Division; DNA; Histocompatibility Antigens Class I; Humans; Male; Phytic Acid; Prostatic Neoplasms; Tumor Cells, Cultured

The expression of prostatic acid phosphatase (PAcP) in three human prostate carcinoma cell lines including LNCaP, DU 145 and PC-3, was studied to explore its potential role as a marker in the progression of prostate cancer. Although Southern blot analysis suggested the presence of PAcP gene in all three prostate carcinoma cell lines, the Northern blot analysis and the reverse transcriptase-polymerase chain reaction (RT-PCR) assay showed that PAcP mRNA can be detected only in LNCaP cells. As one of the major differences between LNCaP cells and PC-3 as well as DU 145 cells is the androgen-sensitivity of LNCaP cells, we then focused on the influence of PAcP expression by the presence of androgen receptor (AR) in human AR cDNA-transfected PC-3 cells and high passages of LNCaP cells. The results demonstrated that the transfection of human AR cDNA into PC-3 cells did not have any detectable effect on the expression of PAcP. Further, in LNCaP cells, while the level of PAcP mRNA diminished upon passage, the AR mRNA level remained approximately the same. Together, these data suggested that the differential expression of PAcP in different prostate carcinoma cells including high passages of LNCaP cells may occur at the transcriptional level and may have little linkage to the expression of AR.

Topics: Acid Phosphatase; Base Sequence; DNA, Complementary; Gene Expression Regulation, Neoplastic; Humans; Male; Molecular Sequence Data; Prostate; Prostatic Neoplasms; Receptors, Androgen; RNA, Messenger; Transfection; Tumor Cells, Cultured

A patient with known prostatic cancer presented with bilateral orbital masses. On CT there was a bulky soft-tissue mass in the cranial aspect of each orbit. An open biopsy revealed undifferentiated tissue that stained strongly positive for prostatic-specific acid phosphatase, confirming the diagnosis of metastatic prostate carcinoma.

Topics: Acid Phosphatase; Adenocarcinoma; Humans; Male; Middle Aged; Orbital Neoplasms; Prostatic Neoplasms; Tomography, X-Ray Computed

The serum levels of creatinine (CR), alkaline phosphatase (ALP), acid phosphatase (ACP) and tartrate inhibitable acid phosphatase (TIAP) were related to Gleason score, TM-category, disease progression and survival in 325 prostatic adenocarcinoma patients followed up for over 12 years. Elevated serum levels of CR, ALP, ACP and TIAP were related to invasive and metastatic disease as well as with a high Gleason score. Elevated serum levels of CR, ALP, ACP and TIAP, all significantly predicted prognosis in a univariate analysis. In the M0 tumours, ACP and TIAP and TIAP had prognostic value, as they did in the T1-2M0 tumours respectively. Cox's multivariate analysis showed that serum creatinine level at diagnosis had independent prognostic value additional to the TM-classification, Gleason score and patient age. In the M0 tumours, ALP had independent prognostic significance additional to the T-category, Gleason score and patient age. In the T1-2M0 tumours, TIAP had independent prognostic value supplementary to the Gleason score, T-category and patient age, whereas in the T1M0 tumours, the gleason score was an independent prognostic parameter. The results indicate that these simple laboratory tests give important prognostic information in prostatic adenocarcinoma.

Topics: Acid Phosphatase; Adenocarcinoma; Adult; Aged; Aged, 80 and over; Alkaline Phosphatase; Creatinine; Follow-Up Studies; Humans; Male; Middle Aged; Multivariate Analysis; Neoplasm Staging; Predictive Value of Tests; Prognosis; Proportional Hazards Models; Prostatic Neoplasms; Retrospective Studies; Risk Factors; Survival Analysis

A 77-year-old male was admitted for the examination of post renal acute renal failure. Blood examination revealed renal dysfunction and elevation of carcinoembryonic antigen (CEA). Computed tomography and retrograde pyelography showed bilateral hydronephrosis due to ureteral stenosis. He died of renal failure and autopsy was done. Histologic findings showed moderately differentiated adenocarcinoma of the prostate associated with endometrioid and mucinous carcinoma, and metastases of retroperitoneal lymph nodes and multiple bones. Immunohistochemically, endometrioid carcinoma was positive for prostatic acid phosphate (PAP) and prostatic specific antigen (PSA), and negative for CEA. Mucinous carcinoma was negative for PAP and PSA, and positive for CEA. Including our case, 29 cases of endometrioid and 32 of mucinous carcinoma of the prostate reported in the Japanese literature are reviewed.

Topics: Acid Phosphatase; Adenocarcinoma; Adenocarcinoma, Mucinous; Aged; Carcinoembryonic Antigen; Carcinoma, Endometrioid; Humans; Immunohistochemistry; Male; Neoplasms, Multiple Primary; Prostate-Specific Antigen; Prostatic Neoplasms

Specimens from 75 cases of prostatic adenocarcinoma of different M.D. Anderson degrees of malignancy were stained immunohistochemically for neuron-specific enolase (NSE), prostatic specific antigen (PSA) and prostatic acid phosphatase (PAP). None of these tumors presented on hematoxylineosin sections any features suggesting neuroendocrine differentiation; nevertheless, 18.7% of the tumors were at least focally NSE positive. Because of the synchronous antigenic expression of the NSE-positive cells to PSA and PAP, the authors suggest that prostatic exocrine and neuroendocrine cells derive from a common precursor stem cell. The possibility of a more aggressive biological behavior of these tumors in comparison to the conventional carcinomas is discussed. The probable clinical necessity for a combined therapeutic approach is also investigated.

Topics: Acid Phosphatase; Adenocarcinoma; Cell Differentiation; Humans; Male; Neurosecretory Systems; Phosphopyruvate Hydratase; Prostate-Specific Antigen; Prostatic Neoplasms

Prostate-specific antigen (PSA) has various advantages over prostatic acid phosphatase (PAP) as a marker for prostate cancer, but its role in prostate cancer mass screening remains controversial. We measured serum PSA in addition to serum PAP determination and digital rectal examination (DRE) in our mass screening program to assess the usefulness of PSA for prostate cancer mass screening.. Serum PSA and PAP measurements and DRE were performed in 1249 patients in mass screening for carcinoma of the prostate in 1989 and 1990. Thirteen cancers were diagnosed. We calculated the mean plus standard deviations (2SD) of the PSA and PAP values of men without cancer, and assessed the usefulness of PSA for prostate cancer screening by using these figures as the upper limit of normal.. The number positive for PSA, PAP and DRE were 39, 36 and 48, respectively. If our screening had been performed without DRE, three cancers would have remained undetected, and the number would have been the same if performed without PSA. If the screening had been performed without PAP, on the other hand, no cancers would have remained undetected. The sensitivities of PSA and PAP were 54% and 23%, respectively. The screening detection rate with DRE and PSA was 0.88%, and with DRE and PAP was 0.64%.. Measurement of serum PSA values with adjustment of the cut-off value was considered more useful than PAP in mass screening for prostate cancer.

Topics: Acid Phosphatase; Aged; Aged, 80 and over; Humans; Male; Mass Screening; Middle Aged; Physical Examination; Predictive Value of Tests; Prostate-Specific Antigen; Prostatic Neoplasms; Rectum; Sensitivity and Specificity

Eighteen previously untreated patients with metastatic carcinoma of the prostate were treated with LHRH analogue. They were divided into 3 groups according to the degree of glandular differentiation. In all groups, a transient rise of PAP and PSA was observed after the LH and testosterone surge. However, relative values of LH, testosterone, PAP and PSA did not differ significantly among the 3 groups. These facts suggest that a transient rise of PAP and PSA is caused by testosterone surge independently from the degree of glandular differentiation after LHRH analogue administration in patients with advanced prostatic cancer.

Topics: Acid Phosphatase; Aged; Aged, 80 and over; Antineoplastic Agents, Hormonal; Humans; Leuprolide; Luteinizing Hormone; Male; Middle Aged; Neoplasm Metastasis; Neoplasms, Hormone-Dependent; Prognosis; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Testosterone

The pretreatment bone scintigrams of 58 patients with prostate cancer with bone metastasis were reviewed and the prognostic value of the initial extent of bone involvement was compared with that of other pretreatment characteristics. The extent of bone metastasis revealed by the scan was related to survival. The serum level of alkaline phosphatase at pretreatment and pathological grade also had some predictive value. Although the pathological grade of primary tumours was related to prognosis, the survival of patients with the same histological grade differed according to the initial extent of disease; patients with extensive disease along with raised serum alkaline phosphatase (twice or more as high as the cut-off value) had poorer prognosis than did those with lower alkaline phosphatase or smaller extent of disease. The extent of bone involvement in combination with serum alkaline phosphatase level therefore apparently has higher prognostic value than does disease extent alone.

Topics: Acid Phosphatase; Aged; Aged, 80 and over; Bone Neoplasms; Humans; Male; Middle Aged; Prognosis; Prostatic Neoplasms; Radionuclide Imaging; Retrospective Studies; Survival Rate

We surveyed the comparative clinical features of patients with stage A1 and stage A2 prostate cancer. Preoperatively, prostate specific antigen (PSA) level was elevated in 50.0% of stage A2 patients as compared to 18.2% of stage A1 patients. Compared to low positivity of prostatic acid phosphatase in 12.5% of stage A2 and in 0% of stage A1, PSA was more sensitive to the presence of incidental carcinoma. During the observation period (mean 35.7 months) no stage A patient died of cancer. No evidence of the disease showed significantly higher rate, and death without cancer was significantly lower in stage A1.

Topics: Acid Phosphatase; Adenocarcinoma; Aged; Combined Modality Therapy; Follow-Up Studies; Humans; Male; Neoplasm Staging; Prognosis; Prostate-Specific Antigen; Prostatic Neoplasms; Retrospective Studies

Primary small cell carcinoma of the prostate is an uncommon condition. Between August 1989 and July 1991 seven patients with this pathology presented to the Repatriation General Hospital, Melbourne. Four of these patients presented by means not previously described. Included in this group is the first reported case of this tumour localized to the prostate gland and apparently cured by radical prostatectomy. The generally poor prognosis and lack of hormonal response associated with this condition warrant a greater awareness of the diagnosis among urologists.

Topics: Acid Phosphatase; Aged; Aged, 80 and over; Biopsy; Carcinoma, Small Cell; Humans; Liver; Lymphatic Metastasis; Male; Phosphopyruvate Hydratase; Prognosis; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Retrospective Studies; Survival Rate

Paneth cell-like change (PCLC) of the prostatic epithelium is considered to be a distinct form of neuroendocrine differentiation characterized by isolated cells or small groups of cells with prominent eosinophilic cytoplasmic granules. We evaluated 300 serially sectioned radical prostatectomy specimens from patients with prostatic adenocarcinoma who had not received prior adjuvant therapy (pathologic stages T2NOMO [177 patients], T3NOMO [100 patients], and TxN1MO [23 patients]). Paneth cell-like change was identified in 30 cases (10%), ranging from 1 to 20 high-power fields/positive case (mean, 4.1 high-power fields/case). There was no correlation of PCLC with prostate volume, prostate weight, Gleason grade, nuclear grade, lymph node metastases, serum prostate-specific antigen levels, cancer volume, area or presence of capsular perforation, seminal vesicle invasion, or glandular mucin (all P > .05), although a positive correlation was seen with cribriform pattern (r = 0.50, P = .0015). Immunohistochemistry revealed cytoplasmic immunoreactivity within cells of PCLC for chromogranin (seven of seven cases), neuron-specific enolase (seven of seven cases), serotonin (six of seven cases), prostate-specific antigen (five of seven cases), and prostatic acid phosphatase (four of seven cases); lysozyme was negative (seven cases). Our findings indicate that PCLC is more common than previously reported, but that it is not associated with tumor grade, serum PSA levels, or pathologic stage. This study also shows that PCLC represents neuroendocrine differentiation, suggesting that the term "Paneth cell-like change" be deleted from the pathologist's lexicon in relation to prostatic adenocarcinoma; a more appropriate term might be "neuroendocrine cells with large eosinophilic granules."

Topics: Acid Phosphatase; Adenocarcinoma; Aged; Chromogranins; Humans; Immunohistochemistry; Male; Middle Aged; Neurosecretory Systems; Phosphopyruvate Hydratase; Prostate-Specific Antigen; Prostatic Neoplasms; Serotonin

To clarify the relation between diurnal rhythm of serum levels of testosterone and two prostatic markers, prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP).. Blood was obtained every four hours during a thirty-two-hour period from fourteen men with untreated prostate cancer.. Serum levels of PSA and PAP showed circadian rhythm in 4 and 5 patients, respectively. About half of the remaining patients, the highest or nearly highest peaks of serum levels of PSA or PAP were observed in the afternoon rather than the morning. In 3 patients, circadian rhythms were not observed in serum levels of PAP, but the fluctuation patterns were the same as those of testosterone and showed synchronous movement. In 7 patients, serum testosterone levels were followed by the same fluctuation pattern for either PSA or PAP after some time delay. Little change in serum levels of PSA was seen throughout the thirty-two-hour period despite large fluctuations of testosterone and PAP levels in 5 patients.. Close relation between the fluctuation in serum levels of PSA and PAP, and that in serum levels of testosterone during diurnal periods could be considered. However, the relationship between serum testosterone levels and those of PSA and PAP was ambiguous because of both the difference in the time delay of PSA and PAP in relation to testosterone and the small fluctuation in PSA despite obvious fluctuations in testosterone and PAP in some cases.

Topics: Acid Phosphatase; Aged; Aged, 80 and over; Circadian Rhythm; Humans; Male; Middle Aged; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Testosterone

DNA ploidy is a significant prognostic factor in patients with prostate cancer. Using DNA/nuclear protein flow cytometry, a subpopulation of tumors with near-diploid DNA is identifiable. The prognostic significance of near-diploidy was examined.. Paraffin-embedded formalin fixed prostate tumor tissue from patients treated at M. D. Anderson Cancer Center with external beam radiation therapy was processed for DNA/nuclear protein flow cytometry. All patients had pretreatment and follow-up serum prostate specific antigen (PSA) levels. Seventy-six specimens were suitable for flow cytometric analysis. Tumors were classified as either diploid (n = 30), near-diploid (n = 24), or nondiploid (n = 22, tetraploid and aneuploid). Median follow-up time was 36 months.. Diploid tumors were associated with a significantly better actuarial outcome at 4 years, compared with near-diploid tumors, using either biochemical relapse (rising PSA) or a composite end point of a rising PSA or clinical relapse (16% versus 52% relapse, P < 0.05, log-rank). Moreover, patients who had nondiploid tumors had the worst prognosis (77% relapse, composite end point). No significant difference was observed between diploid and near-diploid neoplasms regarding actuarial local control, freedom from metastasis, freedom from clinical relapse, or overall survival time. A Cox proportional hazards model, using the composite end point of a rising PSA or relapse, was performed with ploidy categorized as diploid, near-diploid, and nondiploid; pretreatment PSA, DNA ploidy, and tumor grade were found to be independent prognostic factors. When ploidy was categorized as diploid or near-diploid (nondiploid tumors excluded), pretreatment serum PSA and DNA ploidy were independent predictors of outcome. Ploidy remained an independent prognostic factor even when nondiploid tumors were excluded.. These data show that patients who have near-diploid tumors have an intermediate prognosis between the more favorable diploid tumors and the less favorable nondiploid tumors.

Topics: Acid Phosphatase; Adenocarcinoma; Aged; Aged, 80 and over; Cohort Studies; Diploidy; DNA; Flow Cytometry; Follow-Up Studies; Humans; Male; Middle Aged; Neoplasm Staging; Ploidies; Prognosis; Proportional Hazards Models; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Retrospective Studies; Survival Analysis

Nephrogenic adenoma (NA) of the prostatic urethra with involvement of the prostate gland can mimic other small-gland proliferations of the prostate, particularly adenocarcinoma of the prostate. To further characterize this lesion and refine diagnostic criteria we retrospectively reviewed the clinicopathologic features and immunohistochemical findings of eight cases of NA involving the prostate gland seen at The University of Texas M.D. Anderson Cancer Center from 1987 to 1992. The patients' ages ranged from 44 to 76 years (average age, 65 years). Six patients had lower genitourinary tract operations. Follow-up information was available for six patients (follow-up period, 5 to 38 months); only one patient had clinical evidence of recurrence (5 months after surgery). The remaining patients were alive and well with no evidence of disease. Histologically, NA was characterized by a proliferation of small tubules lined by a single layer of cuboidal or flattened cells with clear or eosinophilic cytoplasm. The nuclei were round with fine chromatin and there was no mitotic activity. Nucleoli were generally small, but occasionally prominent. All NA extended into the prostatic parenchyma, raising the possibility that these lesions may represent prostatic small-gland proliferations, particularly prostate adenocarcinoma. However, all cases tested were negative for prostate-specific antigen and prostatic acid phosphatase. Our findings indicate that the histologic features and the use of prostate-specific antigen and prostatic acid phosphatase immunostains will help to distinguish NA of the urethra involving the prostate from other small-gland proliferations (eg, small-acinar adenocarcinoma of the prostate, clear cell adenocarcinoma of the urethra, sclerosing adenosis, atypical adenomatous hyperplasia, florid hyperplasia of mesonephric remnants, simple lobular atrophy, and incomplete basal cell hyperplasia).

Topics: Acid Phosphatase; Adenocarcinoma; Aged; Biomarkers, Tumor; Diagnosis, Differential; Hamartoma; Humans; Immunohistochemistry; Male; Middle Aged; Prostate-Specific Antigen; Prostatic Hyperplasia; Prostatic Neoplasms; Urethral Diseases

A case is presented of a middle-aged man suffering from stage D2 prostate cancer with pulmonary metastases who responded favorably, first, to endocrine combination therapy with the antiandrogen flutamide and an LHRH agonist for 5.5 years, and, second, to the subsequent withdrawal of Flutamide at the time of the progression of the disease. This case has several exceptional features: absence of bone metastases, pulmonary metastatic nodules characterized as focal neuroendocrine differentiation, and a positive response to antiandrogen withdrawal upon relapse of metastases after initial positive response. The concept of escape to androgen blockade and development of androgenic hypersensitivity is discussed.

Topics: Acid Phosphatase; Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Biopsy, Needle; Bone and Bones; Flutamide; Gonadotropin-Releasing Hormone; Humans; Lung Neoplasms; Male; Middle Aged; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Radionuclide Imaging; Sputum; Tomography, X-Ray Computed; Triptorelin Pamoate

Tissue specimens from 150 patients with localised prostatic carcinomas and 116 patients with prostatic carcinomas with distant metastases were analysed for histological grade (WHO and Gleason) and immunoreactivity for prostate acid phosphatase (PAP), prostate-specific antigen (PSA), neurone-specific enolase (NSE), p53 protein, c-erbB-2 protein, cytokeratins (AE1/AE3) and vimentin. After stratification for the presence or absence of distant metastases, multivariate regression analysis revealed that WHO grading was the most powerful independent prognosticator, followed by age and prostate acid phosphatase expression. There was a trend towards reduced survival with decreasing prostate-specific antigen reactivity. The Gleason system showed poor prognostic ability. The analysis predicted reduced survival in the presence of extensive neurone-specific enolase reactivity, mostly because of one case of small-cell carcinoma.

Topics: Acid Phosphatase; Aged; Aged, 80 and over; Humans; Keratins; Male; Middle Aged; Multivariate Analysis; Norway; Prognosis; Prostate-Specific Antigen; Prostatic Neoplasms; Survival Analysis; Vimentin

Prostate inhibin peptide (PIP) is a polypeptide synthesized by the prostate gland that is involved in prostatic growth and differentiation. The objective of this study was to evaluate PIP as an immunocytochemical marker for prostatic adenocarcinoma (PCA) by comparing it with PSA and PAP. A total of 71 cases of primary PCA and 5 cases of metastatic PCA were studied. Primary tumors were specially selected to include a disproportionate number of high-grade tumors. The distribution of cases by Gleason score was 2-5, 14 cases; 6-7, 24 cases; and 8-10, 33 cases. Four metastases were to bone (decalcified tissue) and one to soft tissue. All 71 cases of primary PCA stained positively for the three antibodies tested, with none demonstrating obvious superiority, although individual case variability was seen. In one bone metastasis, staining for PSA was negative, with both PAP and PIP giving positive results. All non-prostatic carcinomas tested were negative. These results indicate that PIP is as sensitive and specific an immunohistochemical marker as PSA and PAP in untreated prostate adenocarcinomas. Further, the androgen-independent nature of PIP may give it an advantage over PSA/PAP in tumors exposed to androgen ablating agents.

Topics: Acid Phosphatase; Biomarkers, Tumor; Carcinoma; Humans; Immunohistochemistry; Inhibins; Male; Neoplasm Metastasis; Neoplasm Proteins; Peptides; Prostate-Specific Antigen; Prostatic Neoplasms; Prostatic Secretory Proteins

We quantified cathepsin D by immunoradiometric assay (IRMA) and quantitative immunohistochemistry in fifteen human prostate cancers, seventeen BPH, and nine normal prostates. The cytosolic cathepsin D concentration was higher in prostatic carcinoma (mean: 31.5 pmol/mg cytosol proteins; range: 10.2-66.2) than in normal prostate (16.0 pmol/mg cytosol proteins; 7.2-25.5; P = 0.01). Prostatic hyperplasia showed intermediate values (20.2 pmol/mg cytosol proteins; 7.6-33.9). Immunostaining of cathepsin D and prostatic acid phosphatase on serial frozen sections of prostate tissues was only observed in glandular epithelial cells. Immunostaining was quantified by computer-assisted image analysis as an quantitative immuno-cytochemical score (QIC score) expressed in arbitrary units (A.U.). QIC scores for cathepsin D were dispersed and had a tendency to be higher in benign prostatic hyperplasia (mean: 178.3 A.U.; range: 95-297) compared to normal prostate (85.2 A.U.; 2-173 P < 0.01) and prostatic carcinoma (90.0 A.U.; 21-179 P = 0.0002). Prostatic cathepsin D levels in cytosols or immunostaining sections were independent of other clinicobiological parameters.

Topics: Acid Phosphatase; Adult; Aged; Aged, 80 and over; Cathepsin D; Cytosol; Humans; Immunohistochemistry; Male; Middle Aged; Neoplasm Metastasis; Neoplasm Staging; Prostate; Prostate-Specific Antigen; Prostatectomy; Prostatic Neoplasms; Reference Values; Urinary Bladder Neoplasms

The authors investigated the sensitivity and specificity of four methods: rectal digital examination, prostate specific antigen (PSA), prostatic acid phosphatase (PAP) and transrectal ultrasound in the diagnosis of 100 prostate cancer and 50 suffering in benign prostatic hypertrophy patients. In 21 patients the prostate cancer was proved by perineal punch biopsy and in 79 cases by biopsy and by TUR as well. Because of its simplicity the rectal investigation has to be first one, after that the PSA has to be determined. The specificity of transrectal ultrasound is low. The determination of PAP in addition of PSA is not necessary.

Topics: Acid Phosphatase; Biopsy; Diagnosis, Differential; Humans; Male; Prostate-Specific Antigen; Prostatic Hyperplasia; Prostatic Neoplasms; Ultrasonography

The dynamics of hormonal levels and tumor markers after the first administration of long-acting luteinizing hormone-releasing hormone (LH-RH) analogue were evaluated in patients with prostate cancer. Eight patients with histopathologically proved prostate cancer who were previously untreated were studied. The surge in plasma testosterone was recognized in 7 patients after the first administration of a long-acting LH-RH analogue, and reached the highest level after the 3rd day in 6 patients and 14th day in 1 patient. The onset of flare-up reaction due to a transient increase in plasma testosterone was recognized in 3 patients, whose clinical symptoms and signs were increased bone pain in 2 patients and acute urinary retention in 1 patient. An abnormal level of serum prostatic acid phosphatase (PAP) and prostate specific antigen (PSA) was observed in 7 of the 8 patients before treatment. The serum PAP and PSA levels slightly increased after treatment in 4 and 3 patients, respectively. These findings suggest that the combination of estrogen or antiandrogen would allow a safer use of long-acting LH-RH analogue to prevent the risk of a flare-up reaction associated with the first administration of long-acting LH-RH analogue.

Topics: Acid Phosphatase; Aged; Aged, 80 and over; Biomarkers, Tumor; Delayed-Action Preparations; Gonadotropins; Goserelin; Humans; Male; Prostate-Specific Antigen; Prostatic Neoplasms; Testosterone

A panel of three monoclonal antibodies that recognize membrane and cytoskeletal antigens expressed by epithelial cells (T16, C26, and AE-1) was used in a sensitive immunohistochemical assay to detect tumor cells in bone marrow aspirates from 20 patients with prostate cancer. Bone marrow aspirates from 2/9 (22%) patients with localized prostate cancer (stage B, 0/5; Stage C, 2/4), and 4/11 (36%) patients with metastatic prostate cancer (Stage D1, 0/7 patients; Stage D2, 4/4 patients) had antigen-positive cells in their bone marrow. The patients with localized disease had conventional examinations for metastases, including radioisotope bone scans and examination of bone marrow cytology, which were negative. The serum prostatic specific antigen (PSA) level appeared to correlate with the presence of micrometastases. Those patients with localized disease and antigen-positive cells in the bone marrow had an average serum PSA level of 26.6 ng/ml, while the average serum PSA level in patients without antigen-positive cells was 12.3 ng/ml. In addition, the number of antigen-positive cells detected appeared to correlate with the stage of disease; patients with Stage C prostate cancer had an average of 10 antigen-positive cells per one million bone marrow elements, while patients with Stage D2 disease had an average of 25 antigen-positive cells per one million bone marrow elements. We have demonstrated that immunohistochemical staining of bone marrow aspirates can detect occult bone marrow metastases in patients with apparently localized prostate cancer. Further follow-up of these and a larger number of patients will be require to determine the potential clinical significance of this finding.

Topics: Acid Phosphatase; Adenocarcinoma; Antibodies, Monoclonal; Biopsy, Needle; Bone Marrow; Humans; Male; Neoplasm Metastasis; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms

This paper reports the results of studies on the possible role of biochemical markers in monitoring the effects of ionizing radiations and in the follow-up of cancer patients submitted to radiotherapy. Three different case series were analyzed: patients with head and neck cancer, prostate carcinoma and residual thyroid tumors or uptaking metastases (131-Iodine therapy). Serum TPA and amylase were serially determined in patients with head and neck or thyroid cancer to measure the radiation damage to the salivary glands. In the former group a statistically significant correlation between the increase of both molecules and the total dose administered after the first day of treatment (2, 3, 4 or 6 Gy) was observed. In patients treated for thyroid cancer the damage to the salivary glands was revealed by an increase in TPA and amylase serum levels, dependent on the dose of 131-Iodine administered. Moreover, an association was demonstrated between pretreatment values of TPA in patients with head and neck tumors and prognosis: patients with values below the cutoff have significantly higher survival rates than those with higher values. In patients with prostate carcinoma PSA was confirmed to have better diagnostic and prognostic value than PAP. Patients with metastases show an inversion or lack of negative trend in PSA levels observed in the disease-free patients. This precedes the clinical diagnosis of metastases by 1 to 15 months.

Topics: Acid Phosphatase; alpha-Amylases; Antigens, Neoplasm; Biomarkers, Tumor; Head and Neck Neoplasms; Humans; Male; Neoplasm Metastasis; Neoplasms; Peptides; Prognosis; Prostate-Specific Antigen; Prostatic Neoplasms; Thyroid Neoplasms; Tissue Polypeptide Antigen

In this study, we quantitatively evaluated the intensity and extent of prostate-specific acid phosphatase in immunocytochemically stained prostate carcinoma tissue sections by using a dual-wave-length-based image processing technique. Tissue sections were doubly stained in a standard way, i.e., prostate-specific acid phosphatase was immunocytochemically labeled by peroxidase-antiperoxidase (PAP) technique using diaminobenezidene (DAB) as the substrate and hematoxylin as a nuclear counterstain. Statistical analysis in this study indicated that the quantitative measures of the prostate-specific acid phosphatase staining (PAP-DAB) are reproducible. We found that the quantitative intensity was generally proportional to the subjective intensity (graded as 1 to 4+) of PAP-DAB. Although the quantitative extent measurements compared with the subjective estimates of the percentage of tumor showing staining with PAP-DAB had a similar tendency, there were significant overlaps between extent of tumor staining falling in the mid-ranges. Because subjective grading of immunocytochemical prostate-specific acid phosphatase has been thought to be a useful marker of tumor differentiation in patients with prostate carcinoma, we also evaluated the relationship of the quantitative measures of PAP-DAB staining to other predictors of patient outcome, including histologic grades (Gleason score and MD Anderson grading scheme) and clinical stage. We confirmed that quantitative intensity and extent of PAP-DAB staining were independent of histologic grades and stage, just as the subjective measures of intensity and extent were found to be. Possible explanations of this lack of correlation are discussed.

Topics: 3,3'-Diaminobenzidine; Acid Phosphatase; Data Interpretation, Statistical; Humans; Image Processing, Computer-Assisted; Immunoenzyme Techniques; Male; Microscopy; Neoplasm Staging; Prostate; Prostatic Neoplasms; Reproducibility of Results; Staining and Labeling

Early whole body bone scintigraphy was performed on 25 patients with prostatic cancer (15 cases with bone metastases and 10 cases without bone metastasis) to obtain anterior and posterior whole body images five minutes after administration of 99mTc-HMDP. The results were compared with the findings of routine bone scintigraphy after three hours, and the usefulness of the above method for the diagnosis of bone metastasis from prostatic cancer was evaluated. In cases in which increased activity was found in the upper and lower lumbar vertebrae by routine bone scintigraphy but no abnormality was seen by early whole body bone scintigraphy, senile degenerative bone changes such as spondylosis deformans were observed by bone radiography. In cases with multiple bone metastases, abnormal multiple accumulations were found by both early whole body bone scintigraphy and routine bone scintigraphy. In addition, in cases showing super bone scan, high accumulation in the skeletal system had already been detected by early whole body bone scintigraphy. When the courses before and after treatment in nine cases of multiple bone metastases were passaged from the results of early whole body bone scintigraphy and from changes in tumor markers (prostatic specific antigen, gamma-semino protein and prostatic acid phosphatase), increased activity and the appearance of new hot spots as well as an increase in tumor markers were detected by early whole body scintigraphy in three of the four advanced cases, whereas decreased accumulations and a decrease in and normalization of tumor markers were observed in five improved cases.

Topics: Acid Phosphatase; Aged; Aged, 80 and over; Biomarkers, Tumor; Bone and Bones; Bone Neoplasms; Humans; Male; Middle Aged; Prostate-Specific Antigen; Prostatic Neoplasms; Radionuclide Imaging; Whole-Body Counting

The inversion of PSA/PAP ratio is not common in patients with prostate cancer. Of 215 patients, 7 showed PSA levels below those of PAP (3.2%). All patients had metastatic disease at the time of diagnosis, 57% in multiple organs and tissues, with a Gleason value in all cases 4. Forty-three percent showed no early response to hormone therapy; mean survival interval recorded in these 7 patients was 21 months. Such a situation may suggest a poor prognosis for this neoplasia.

Topics: Acid Phosphatase; Aged; Clinical Enzyme Tests; Humans; Male; Middle Aged; Neoplasm Metastasis; Prognosis; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Survival Analysis

The present status of tumor markers in prostate cancer, especially prostate-specific antigen (PSA), for diagnosis and follow-up of prostate cancer patients was reviewed. Due to tissue-specific protein of PSA as well as PAP, serum PSA levels may increase in patients with benign hyperplasia (BPH) which is the disease necessary for differential diagnosis from prostate cancer. Therefore, it has been believed to be difficult to differentiate early stages of prostate cancer from BPH using only PSA determination. However, with the use of recently developed assay systems, the detection of PSA-protease inhibitor complex, or PSA-density, the detection of early stages of prostate cancer may be possible. In following up prostate cancer patients, serially determined PSA is one of the best tools to evaluate treatment response and early detection of disease progression.

Topics: Acid Phosphatase; Biomarkers, Tumor; Counterimmunoelectrophoresis; Diagnosis, Differential; Humans; Immunoenzyme Techniques; Male; Prostate; Prostate-Specific Antigen; Prostatic Hyperplasia; Prostatic Neoplasms; Prostatic Secretory Proteins; Prostatitis; Proteins; Radioimmunoassay; Seminal Plasma Proteins

From 1978 to 1982, 172 patients with stages T1 to 3NxM0 prostate cancer were included in a surveillance protocol with deferred treatment on symptomatic progression. Median patient age at diagnosis was 68 years (range 38 to 89 years). Mean followup was 80 +/- 32 months. Of the patients 58% had local and 19% had distant progression, and 52% had received treatment at followup. Disease specific survival rate at 10 years was 80% for the total series, 84% for the subgroup with stage T1 or T2 tumor and 92% for those with stage T1 or T2 tumor who were less than 70 years old at diagnosis. For the subgroup with stage T3 tumor the disease specific survival rate at 9 years was 70%. In all subgroups the competing mortality rate was higher than the prostate cancer mortality rate. Deferred treatment appears to be an acceptable option for patients with tumor clinically confined to the prostate and a life expectancy of 10 years or less.

Topics: Acid Phosphatase; Adenocarcinoma; Adult; Aged; Aged, 80 and over; Cause of Death; Disease Progression; Disease-Free Survival; Follow-Up Studies; Humans; Male; Middle Aged; Neoplasm Metastasis; Neoplasm Staging; Population Surveillance; Prospective Studies; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Survival Rate; Sweden

To determine if tissue expression of prostate-specific antigen (PSA), prostatic acid phosphatase (PAP), and a prostate-associated monoclonal antibody (TURP-27) is retained after irradiation therapy and to compare these results with serum levels.. Immunohistochemical tests were performed on prostatic tissue obtained by needle biopsy or transurethral resection prior to and following definitive irradiation therapy for clinically localized prostatic carcinoma. PSA, PAP, and TURP-27 were studied. Results were compared with serum PSA and PAP values.. All 20 preirradiation specimens stained positively for PSA and PAP; 19 of 20 stained for TURP-27. All 5 of the initial post-treatment biopsy specimens that showed recurrent tumor stained for all 3 markers. In 2 cases, staining for the 3 markers was greatly diminished. Only 8 of 15 post-treatment biopsy-negative specimens stained for all 3 markers. Six of 15 demonstrated loss of tissue expression for all 3 antigens. One specimen stained for PAP and TURP-27 but failed to stain for PSA. Serum PSA levels paralleled tissue expression in recurrent tumor specimens. However, 3 of the post-treatment biopsy-positive cases with PAP expressing tissue had normal serum PAP levels.. No cases of recurrent tumor with marker-negative tissue were identified. However, benign epithelial prostate cells appear to sustain sufficient damage from irradiation to lose the capacity to produce certain proteins. Diminished contribution of benign glands to circulating PSA, in addition to decreased expression in malignant tissues, may explain the lower than anticipated serum PSA levels in patients who progress after irradiation therapy.

Topics: Acid Phosphatase; Adenocarcinoma; Antibodies, Monoclonal; Antigens, Neoplasm; Biomarkers, Tumor; Biopsy, Needle; Humans; Immunoenzyme Techniques; Male; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Staining and Labeling; Time Factors

Expression of human prostatic acid phosphatase (ACPP) and prostate specific antigen (PSA) genes in prostatic carcinoma (CAP) and benign prostatic hyperplasia (BPH) was investigated by northern blot analyses. The expressions of ACPP and PSA, as well as the glycolytic enzymes glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and lactate dehydrogenase-muscle (LDH-A), were elevated significantly in prostatic carcinoma when compared with the expressions of these genes in benign prostatic hyperplasia in the same patient. The expression of the actin gene in both neoplastic and benign hyperplasia remained the same.

Topics: Acid Phosphatase; Aged; Blotting, Northern; DNA Probes; Gene Expression; Glyceraldehyde-3-Phosphate Dehydrogenases; Humans; Isoenzymes; L-Lactate Dehydrogenase; Male; Middle Aged; Nucleic Acid Hybridization; Prostate; Prostate-Specific Antigen; Prostatic Hyperplasia; Prostatic Neoplasms

Prostatic specific antigen (PSA) and prostatic acid phosphatase (PAP) are the tumor markers for monitoring disease progression or improvement in patients with prostate adenocarcinoma. The clinical utility of PSA and PAP for early detection of prostate adenocarcinoma, however, requires distinction between prostate adenocarcinoma and prostate nodular hyperplasia. The serum PSA and PAP levels were measured in 20 men with histologically proven prostate adenocarcinoma and 28 men with histologically proven prostate nodular hyperplasia. Patients' blood samples were collected 1 to 7 days prior to the prostate examination, which included a rectal digital examination, transurethral resection, cytoscopy, and prostate biopsy. Sensitivity, specificity, and predictive values of positive and negative results for the discrimination of prostate adenocarcinoma from prostate nodular hyperplasia were 85%, 89%, 85%, and 29%, respectively, for serum PSA (cutoff level: 10 ng/mL) and 40%, 96%, 89%, and 69%, respectively, for serum PAP (cutoff level: 10 ng/mL). Results indicate that marked elevation of serum PSA suggests prostate adenocarcinoma and that serum PSA can discriminate prostate adenocarcinoma from prostate nodular hyperplasia better than serum PAP.

Topics: Acid Phosphatase; Adenocarcinoma; Adult; Aged; Diagnosis, Differential; Humans; Male; Middle Aged; Prostate; Prostate-Specific Antigen; Prostatic Hyperplasia; Prostatic Neoplasms; Sensitivity and Specificity

Estramustine phosphate (EMP) and flutamide (FL) were used as reversible preoperative hormonal drugs in the surgical treatment of patients with localized prostate cancer.. The authors descriptive and quantitatively examined the morphologic and immunohistochemical changes in 40 of 200 step-sectioned radical prostatectomies, obtained after treatment with EMP (25 patients) and with FL (15 patients). Of these, 28 pretreatment needlecore biopsies were available.. Every specimen contained adenocarcinoma. Understaging was found in 50% of the cases and a higher Gleason score in 70%. Benign glands underwent atrophy and squamous metaplasia. Treated tumors showed cytoplasmic vacuolization, nuclear pyknosis, fibrosis and lymphocytic infiltrates. The EMP group had an 84% (P < 0.05) higher mean total regression score than the FL group. Estramustine phosphate induced a 56% (P < 0.05) and a 34% decrease in tumoral prostate specific antigen and prostate specific acid phosphatase intensity scores, respectively, versus 29% and 32% after FL. The mean proliferating cell nuclear antigen (PCNA) labeling index and the mean mitotic index of the EMP group were 52% (P < 0.05) and 70% (P < 0.05) lower than those measured in the FL group. Each FL-treated tumor and 92% of EMP-treated tumors expressed chromogranin A (ChrA); ChrA labeling correlated significantly with PCNA labeling. Seventy-six percent of EMP-treated specimens revealed venous thrombosis.. Estramustine phosphate induces important morphologic and immunohistochemical changes in prostate cancer with an apparent decrease of secretory and proliferative activity when compared with FL-treated tumors. These changes represent pitfalls in the diagnosis and grading of treated carcinomas. Nearly every treated adenocarcinoma of the prostate has neuroendocrine differentiation, showing increasing ChrA labeling with higher tumor stage. A significant correlation between tumor proliferation and neuroendocrine differentiation was noticed in this small cohort of patients. There was a high incidence of periprostatic venous thrombosis after EMP treatment.

Topics: Acid Phosphatase; Adenocarcinoma; Aged; Chemotherapy, Adjuvant; Chromogranin A; Chromogranins; Estramustine; Flutamide; Humans; Immunohistochemistry; Male; Mitosis; Neoplasm Staging; Premedication; Proliferating Cell Nuclear Antigen; Prostate; Prostate-Specific Antigen; Prostatectomy; Prostatic Neoplasms

Metastatic pulmonary adenocarcinoma was found in a 79-year-old man, who had symptoms of general malaise and poor appetite. An extensive work-up including a transurethral resection of the prostate, failed to establish the primary site of the malignancy. By administering chlormadinone acetate for prostatic hypertrophy, the pulmonary metastases improved dramatically. The tumor cells in the lung, which had previously been obtained by transbronchial lung biopsy, stained positive for prostatic acid phosphatase and prostatic specific antigen. These data suggested that prostatic carcinoma had metastasized to the lung. The prostatic carcinoma was finally confirmed at autopsy.

Topics: Acid Phosphatase; Adenocarcinoma; Aged; Biomarkers, Tumor; Humans; Immunohistochemistry; Lung; Lung Neoplasms; Male; Prostate-Specific Antigen; Prostatic Neoplasms

The ALVA-41 cell line was derived from a bony metastasis from a human prostatic carcinoma. The line has a number of distinct, advantageous properties that should make it useful as a tool for the study of prostate cancer. It grows rapidly and is easy to work with. It has receptors for androgens and glucocorticoids but not for estrogens. Its growth is enhanced by physiological concentrations of dihydrotestosterone. It does not secrete prostate specific antigen, but does secrete prostatic acid phosphatase. Further, the secretion of prostatic acid phosphatase is enhanced by dihydrotestosterone.

Topics: Acid Phosphatase; Adenocarcinoma; Bone Neoplasms; Cell Adhesion; Cell Division; Cholestenone 5 alpha-Reductase; Humans; Male; Oxidoreductases; Prostate-Specific Antigen; Prostatic Neoplasms; Receptors, Androgen; Receptors, Estrogen; Receptors, Glucocorticoid; Tumor Cells, Cultured

Serum tissue polypeptide-specific antigen (TPS), prostate-specific antigen (PSA), and prostatic acid phosphatase (PAP) concentrations were serially measured in 31 prostate cancer patients with bone metastases who had relapsed following hormonal therapy. Of these subjects 7 had well-differentiated cancer (G1), 13 patients were assessed to have moderately differentiated tumor (G2) while in 11 subjects poorly differentiated tumor (C13) was found. With increasing tumor grade (G1 to G3), a proportional increase in mean TPS value was found while the increase in respective PAP serotest values was not linear. Simultaneously measured mean PSA values showed a curved effect. Both PSA and PAP serotest concentrations depend on the respective hormone-dependent gene expressions that gradually decrease with tumor dedifferentiation. Therefore, in progressive hormonally treated stage D2 prostate cancer patients an androgen-independent TPS serotest seems to be a useful clinical addition for monitoring protocols. The combined use of TPS, PSA, and PAP seems to give a better reflection of tumor status. According to the bone scan data metastatic tumor mass in G3 carcinomas was virtually equal to cancer burden in G2 tumors. Hence, the marked elevation of TPS serotest values in G3 adenocarcinomas could not be attributed to greater tumor mass but was most likely due to an increase in proliferation rate. Some authors have recently proposed cytokeratins 8, 18, and 19 to be the origin of TPS serum findings. However, cytokeratin content has been proven to be lower in G3 tumors than in better-differentiated neoplasms.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acid Phosphatase; Adenocarcinoma; Biomarkers, Tumor; Humans; Male; Neoplasm Recurrence, Local; Neoplasm Staging; Peptides; Prostate-Specific Antigen; Prostatic Neoplasms

In a retrospective analytical study the authors evaluated in 86 patients, mean age 69 years (range 55-85 years), with a newly diagnosed untreated prostate carcinoma the sensitivity, specificity, positive and negative predictive value of specific prostatic antigen (PSA), acid phosphatase (AP), alkaline phosphatase (AP') and pain in relation to possible affection of bones by secondaries. The authors found a highly negative predictive value for assessment of bone metastases when PSA values were lower than 10 ng/ml (96%), at levels under 20 ng/ml (94%) and a highly positive predictive value at levels higher than 50 ng/ml (97%). When AP and AP' are negative and there is no pain the occurrence of secondaries is of low probability. These results make it possible to differentiate some patients where scintigraphy of the skeleton is not inevitable. This procedure can be applied above all in patients where radical prostatectomy is not indicated.

Topics: Acid Phosphatase; Aged; Aged, 80 and over; Alkaline Phosphatase; Bone Neoplasms; Humans; Male; Middle Aged; Predictive Value of Tests; Prostate-Specific Antigen; Prostatic Neoplasms; Retrospective Studies; Sensitivity and Specificity

To compare levels of gamma-seminoprotein (gamma-Sm) assayed by original and revised assay systems, blood was obtained every 4 h over a 32-h period from 8 untreated prostate cancer patients. Serum levels of prostate specific antigen (PSA) were also examined. In 6 patients, the coefficient of variation (CV) of the serum levels assayed by the revised assay was significantly different from that of the intra-assay samples. In contrast, the CV of the gamma-Sm serum levels assayed by the original assay differed significantly from that of the intra-assay samples in only 2 patients. The fluctuations in gamma-Sm assayed by the revised assay were, at least in part, similar to those of the PSA serum levels in all patients. The mean CV of the gamma-Sm serum levels assayed by the revised assay was significantly larger than that for levels measured by the original assay. After treatment, the rate of decrease in gamma-Sm serum levels determined by the original assay differed from that in the serum levels of PSA and prostatic acid phosphatase. These results indicate that the original assay for gamma-Sm do not detect diurnal differences in serum gamma-Sm levels, even at levels below 20 ng/ml. These observations indicate that the analysis of data obtained using the original gamma-Sm kit should be interpreted with caution.

Topics: Acid Phosphatase; Aged; Aged, 80 and over; Biological Assay; Biomarkers, Tumor; Circadian Rhythm; Humans; Male; Middle Aged; Prostate-Specific Antigen; Prostatic Neoplasms; Prostatic Secretory Proteins; Proteins; Reagent Kits, Diagnostic; Seminal Plasma Proteins

We report a case of advanced prostate cancer in which an initial response to hormonal therapy with surgical castration and estramustine phosphate (EMP) was followed by disease progression, as shown by sequential elevations in serum prostate specific antigen (PSA) and prostate acid phosphatase (PAP) and the development of new symptoms, during maintenance endocrine and anti-cancer chemotherapy. Discontinuation of EMP resulted in sustained reductions in serum PSA and PAP levels and a sustained improvement in symptoms.

Topics: Acid Phosphatase; Adenocarcinoma; Biomarkers, Tumor; Bone Neoplasms; Castration; Estramustine; Humans; Lung Neoplasms; Male; Middle Aged; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms

The 111In-labeled monoclonal anti-prostatic acid phosphatase (PAP) monoclonal antibody F(ab')2 fragment was used for the radioimmunodetection of prostate cancer in two different patient groups: 15 patients with surgically verified T1-2 prostate cancer were imaged prior to staging lymphadenectomy and total prostatectomy using lymphatic administration (intraprostatic (ipr) injection), and 15 patients with verified metastatic prostatic cancer were imaged after intravenous (i.v.) injection. The patients were studied on several occasions (at 0-180 hours) after injecting a 1 mg MoAb fragment labeled with 75-150 MBq111In (DTPA-chelation). The extirpated tissues were counted for radioactivity, and studied immunohistochemically (IHC) and histologically. The anti-PAP MoAb was labeled with high efficiency (87-99%) and it demonstrated good immunoreactivity (90-95%) and a high affinity to the target antigen. In the excised prostates, cut into 12-18 smaller pieces, there was a clear correlation between the PAP content (as detected by IHC) and absolute radioactivity (% ID of 111In anti-PAP/g prostate). However, there was no correlation between radioactivity and the amount of cancer tissue (% of histological slices) inside the removed prostate tissue. In the pharmacokinetic studies, maximum activity in the serum was obtained within 3-5 hours after ipr injection; after that the kinetic behavior was similar to that after i.v. injection. After i.v. injection, two components could be distinguished the pharmacokinetic curves; the half-lives for mean distribution and elimination were 0.62 and 35.6 hours, respectively. The mean distribution half-life as well as the AUC from the pharmacokinetic curves correlated significantly with serum PAP (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acid Phosphatase; Antibodies, Monoclonal; Half-Life; Humans; Indium Radioisotopes; Male; Neoplasm Staging; Prostate; Prostatic Neoplasms; Radioimmunodetection; Tissue Distribution

Current clinical trials in disseminated prostatic cancer mostly use M0 or M1 to identify two prognostically different groups of patients. Soloway et al. [Cancer 1988;61:195-202] have shown a significant difference in survival depending on the extent of disease (EOD) on bone scan in M1 disease. Seventy-three prostatic cancer patients with bone-scan-proven metastases (T0-4 Nx M1 G1-3) from the Aust-Agder County in Norway with observation time 2-9 years were followed. The impact of T stage, grade, serum acid phosphatase status and EOD on survival was analyzed. EOD was assessed according to Soloway et al. No statistically significant difference could be demonstrated according to T stage or histological grade. A statistically significant difference in survival could be demonstrated both for normal versus elevated serum acid phosphatase and for EOD. EOD I/II had a better prognosis than EOD III/IV. Stratification of patients in EOD categories seems relevant, but the relative importance of the different EOD categories is not yet established.

Topics: Acid Phosphatase; Aged; Bone Neoplasms; Humans; Male; Neoplasm Staging; Prognosis; Prostatic Neoplasms; Risk Factors; Survival Analysis; Survival Rate

We have established two new epithelial cell lines (NRP-152, NRP-154), with markedly different properties, from the dorsal-lateral prostate of Lobund/Wistar rats treated with N-methyl-N-nitrosourea and testosterone propionate. NRP-152 cells do not form tumors in athymic mice and retain many of the properties of normal prostatic epithelial cells. They produce prostatic acid phosphatase, have functional androgen receptors, and require the combination of several growth factors in addition to serum for optimal growth. Their growth is stimulated by epidermal growth factor, insulin, dexamethasone, cholera toxin, dihydrotestosterone, and testosterone, and their growth is inhibited by transforming growth factor beta s and retinoic acid. These cells also respond to 1,25-dihydroxyvitamin D3 with an early growth stimulation followed by growth inhibition at later times. In contrast, tumorigenic NRP-154 cells lack detectable androgen receptor mRNA and have less stringent growth factor requirements for optimal growth. Growth of NRP-154 cells is stimulated by dexamethasone and insulin, inhibited by transforming growth factor beta 1, but not significantly altered by epidermal growth factor, cholera toxin, dihydrotestosterone, retinoic acid, or 1 alpha,25-dihydroxyvitamin D3. Our data suggest that the NRP-152 and NRP-154 cell lines are suitable systems for analysis of normal prostate growth and prostatic carcinogenesis.

Topics: Acid Phosphatase; Animals; Calcitriol; Cell Division; Cell Line; Dihydrotestosterone; Epithelium; Karyotyping; Male; Methylnitrosourea; Mice; Mice, Nude; Prostate; Prostatic Neoplasms; Rats; Rats, Wistar; Receptors, Androgen; Transforming Growth Factor beta; Tretinoin; Tumor Cells, Cultured

Prostatic acid phosphatase (PAcP) is a prostate epithelium-specific differentiation antigen. It has been demonstrated that human PAcP exhibits endogenous protein tyrosine phosphatase (PYP) activity, and that it represents the major PYP activity in normal prostate cells. Thus, it has been postulated that cellular PAcP may play a role in the tyrosine phosphorylation-mediated signal transduction. In this paper, we used LNCaP human prostate carcinoma cells, which express the endogenous PAcP, to study changes in cellular PAcP activity during cell growth. Our results demonstrated that PAcP activity increased when the cells reached confluence. Stimulation of cell growth by fresh culture medium or 5 alpha-dihydrotestosterone (DHT), a classical stimulator of prostate epithelial growth, resulted in a decline in PAcP activity. Moreover, transfection of PC-3 cells, which do not express PAcP, with a PAcP-expressing vector led to diminished cellular growth rate. These data established an inverse relationship between the cellular level of PAcP and the cell growth rate, suggesting that PAcP may be involved in regulating the growth of human prostate carcinoma cells.

Topics: Acid Phosphatase; Cell Division; Humans; Male; Prostate; Prostatic Neoplasms; RNA, Messenger; Tumor Cells, Cultured

The expression of human prostatic acid phosphatase (PAcP), a differentiation antigen of prostate epithelial cells, has been proposed to be regulated by androgen. We investigated this regulatory mechanism at the post-transcriptional level in LNCaP human prostate carcinoma cells, the only cultured cells that express PAcP. Our results demonstrated that the level of PAcP mRNA decreased when the cell density increased. Further, 5 alpha-dihydrotestosterone, an active form of the endogenous androgen, stimulated the PAcP mRNA level in low-density cells; while, caused a decrease in high-density cells. Thus, in LNCaP human prostate carcinoma cells, cell density could modulate PAcP expression at the mRNA level including androgen regulation.

Topics: Acid Phosphatase; Androgens; Cell Count; Dihydrotestosterone; Gene Expression Regulation; Humans; Male; Prostate; Prostatic Neoplasms; RNA, Messenger; Tumor Cells, Cultured

Topics: Acid Phosphatase; Humans; Male; Prostate-Specific Antigen; Prostatic Neoplasms

Serial serum prostate tumor markers (acid phosphatase, prostate-specific antigen-Yang, prostate-specific antigen-Hybritech, lipid-associated sialic acid in plasma, and tissue polypeptide antigen) were obtained every four hours during a twenty-four-hour interval from men with Stage D adenocarcinoma of the prostate. No therapeutic or diagnostic manipulations occurred during sample procurement, so that the amount of fluctuation in these serum prostate cancer markers could be determined. The average co-efficient of variation for acid phosphatase 28.8, prostate-specific antigen-Yang 8.85, prostate-specific antigen-Hybritech 7.2, lipid-associated sialic acid in plasma (LASA-P) 6.19, and tissue polypeptide antigen (TPA) 14.75 indicate that prostate-specific antigen determined by either method fluctuates minimally, indicating stability and, because it is prostate-cancer specific, is the most useful tumor marker tested.

Topics: Acid Phosphatase; Adenocarcinoma; Aged; Aged, 80 and over; Biomarkers, Tumor; Humans; Lipids; Male; Middle Aged; N-Acetylneuraminic Acid; Neoplasm Staging; Peptides; Prostate-Specific Antigen; Prostatic Neoplasms; Sialic Acids; Time Factors; Tissue Polypeptide Antigen

The impact of positive and negative surgical margins of resection on the interval to and incidence of progression was analysed in 172 patients after radical retropubic prostatectomy combined with lymphadenectomy; 56 had positive margins. Lateral and apical positive margins were evaluated separately. The status of surgical margins was correlated with other prognostic factors, such as the T category, the presence or absence of seminal vesicle invasion and the G category. This analysis showed that positive and negative margins significantly influenced time to progression independently of the other prognostic factors. Positive margins at the apex contrary to lateral margins did not significantly influence time to progression. This may be due to the definition of the status of apical margins used in this analysis. A total of 108 patients underwent a nerve-sparing radical prostatectomy, which did not lead to a higher incidence of positive margins than the standard procedure. Prostate specific antigen accurately predicted tumour recurrence after radical prostatectomy. A rise of > or = 1.0 ng/ml preceded other evidence of recurrence by a mean of 11 months.

Topics: Acid Phosphatase; Aged; Biomarkers, Tumor; Humans; Lymph Node Excision; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Invasiveness; Neoplasm Recurrence, Local; Prospective Studies; Prostate; Prostate-Specific Antigen; Prostatectomy; Prostatic Neoplasms

25 patients with measurable or evaluable metastatic prostate cancer, progressive after hormonal treatment, were treated weekly with carboplatin 150 mg/m2 intravenously. The weekly schedule allowed higher dose intensity carboplatin administration with respect to the common monthly cycles. Toxicity was manageable even in elderly patients with extensive bone metastases and consisted primarily of myelosuppression. 4 out of 24 evaluable patients (17%) had a partial response and 12 (50%) had disease stabilisation. The median response duration was 7 months. Prostate-specific antigen and prostatic acid phosphatase serial values showed a correlation with disease response in only 47 and 50% of patients, respectively. These results suggest that carboplatin possesses a moderate but definite activity in prostate cancer patients.

Topics: Acid Phosphatase; Aged; Biomarkers, Tumor; Bone Neoplasms; Carboplatin; Drug Administration Schedule; Drug Resistance; Hormones; Humans; Infusions, Intravenous; Liver Neoplasms; Lymphatic Metastasis; Male; Middle Aged; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms

Carcinoma of the prostate is the commonest malignancy of the genitourinary tract in the male and is frequently associated with metastatic bone disease. Serial isotope bone scans for screening secondary deposits are not cost-effective. We have evaluated the serum prostate markers prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP) as an alternative to conventional serial bone scanning in 129 patients with newly diagnosed prostate cancer over a period of 3 years. Although serum PSA did not reflect local tumour burden at presentation, it was significantly elevated in those who presented with stage D disease (p < 0.01). 45 patients presented de novo with metastatic bone deposits and a further 18 patients developed metastases during the study period. The sensitivity of PSA in detecting secondary deposits at presentation for levels in excess of 100 micrograms/l was 93.75%, the positive predictive value 95.7% and the negative predictive value for levels less than 5 micrograms/l was 90.6%. During the follow-up period the sensitivity was 94.4%, the positive predictive value 100% and the negative predictive value 100%, with a median lead time of 3 months in predicting metastases in the 18 patients with progressive disease. When compared with PAP, PSA was found to be a statistically superior marker of bone metastases both at presentation and follow-up (p < 0.05). We recommend that PAP measurements are no longer necessary and should be replaced by PSA, and that serial serum PSA estimations should determine the need for future isotope bone scans in the patient with established prostate cancer.

Topics: Acid Phosphatase; Bone and Bones; Bone Neoplasms; Follow-Up Studies; Humans; Male; Predictive Value of Tests; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Radionuclide Imaging; Sensitivity and Specificity; Technetium Tc 99m Medronate; Time Factors

In order to characterize the effects of growth factors on the regulation of expression of the genes coding for prostatic differentiation markers, prostatic acid phosphatase and prostate-specific antigen, we studied changes occurring in the biosynthesis of these enzymes in LNCaP prostatic cancer cells treated with growth factors. Epidermal growth factor was found to reduce the secretion of prostatic acid phosphatase and prostate-specific antigen by the cells, as the result of lowered steady-state levels of the corresponding messenger RNAs (mRNAs). In addition, epidermal growth factor (EGF) interfered with the androgen regulation of these genes. EGF evoked these changes in a concentration- and time-dependent fashion, in both the presence and absence of serum and most likely through interactions with the epidermal growth factor receptor, inasmuch as similar effects were achieved by treating the cells with transforming growth factor alpha. The regulation of the human glandular kallikrein 1 gene was quite similar to the regulation of the prostate-specific antigen gene. In addition to the expression of the genes coding for prostatic secretory proteins, the amount of the human androgen receptor mRNA was down-regulated by EGF. This reduction was more pronounced than the autologous down-regulation of human androgen receptor (hAR) mRNA by androgen and could be maintained for at least 5 days. In the presence of androgen, some of the effects of EGF and transforming growth factor alpha on the levels of androgen-regulated mRNAs may be due to down-regulation of the expression of the hAR gene. Transforming growth factor beta 1, which blocked the growth induction of LNCaP cells by EGF, increased the level of prostatic acid phosphatase and hAR mRNAs, but when given to the cells together with EGF its up-regulatory effect could not be discerned. In summary, regulation of the prostatic acid phosphatase and prostate-specific antigen genes is a complex matter, inasmuch as androgens and growth factors regulate the levels of the mRNAs originating from them. Furthermore, the interactions between the androgen-regulatory system and the growth factor-regulatory systems are likely to be at multiple levels in prostatic cells, as suggested by the modulation of the hAR gene expression by these growth factors.

Topics: Acid Phosphatase; Base Sequence; Carcinoma; Epidermal Growth Factor; Gene Expression Regulation; Humans; Kallikreins; Male; Molecular Sequence Data; Prostate-Specific Antigen; Prostatic Neoplasms; Receptors, Androgen; RNA, Messenger; Transforming Growth Factor alpha; Transforming Growth Factor beta; Tumor Cells, Cultured

Metastatic involvement of pelvic lymph nodes in carcinoma of the prostate alters the prognosis and treatment of this disease. Our goal was to determine if additional techniques, such as immunohistochemical staining, could detect occult microscopic metastatic nodal disease not seen with routine hematoxylin and eosin staining. We examined paraffin embedded lymph nodes from 43 patients with clinical stage A or B carcinoma of the prostate who were candidates for radical prostatectomy and who underwent modified pelvic lymph node dissection with frozen section hematoxylin and eosin staining. Immunohistochemical staining for prostate specific antigen and prostate specific acid phosphatase was performed on the lymph nodes. Monoclonal antibodies to cytokeratins were used to confirm the epithelial origin of the prostate cells. An average of 9 lymph nodes and 42 histological sections per patient were stained. Based on routine hematoxylin and eosin staining the pathological staging was stage A in 3, stage B in 20, stage C in 9 and stage D1 in 11 cases. There were 17 well, 16 moderately and 10 poorly differentiated carcinomas. In 31 of 32 patients with negative nodes no occult metastases could be identified. One patient with poorly differentiated stage C cancer demonstrated occult nodal deposits by prostate specific acid phosphatase and not by prostate specific antigen. In the 11 stage D1 cancer patients immunohistochemical staining confirmed all malignant deposits and additional metastatic lesions were detected in only 1 patient. Unlike other carcinomas, such as breast, in which immunohistochemical staining yields a 14 to 37% occult metastasis rate, these data suggest that occult nodal metastases are infrequently seen in carcinoma of the prostate.

Topics: Acid Phosphatase; Adenocarcinoma; Humans; Immunoenzyme Techniques; Lymph Nodes; Lymphatic Metastasis; Male; Pelvis; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms

A new human prostate tumor cell line (ALVA-31) has been established from a biopsy specimen of primary tumor obtained during prostatectomy. The cell line has been maintained for more than 48 months in stable growth. The in vitro doubling time was determined to be approximately 26 hr. The chromosome number ranged from 24-112, with a modal number of 59 tested over several time points throughout continuous culture. Karyotypic analysis of late-passaged cells demonstrated approximately 70 human chromosomes, 8-14 markers, and two X chromosomes without a Y chromosome. Prostatic origin was confirmed by the expression of both prostate specific antigen and prostatic acid phosphatase, using specific antisera and immunoradiolabelling techniques. Prostate tumor xenografts were grown in intact male, castrate male, and female athymic mice; however, the rate of tumor growth was clearly dependent upon serum testosterone levels.

Topics: Acid Phosphatase; Animals; Biomarkers; Cell Division; Cytosol; Female; Humans; Isoenzymes; Karyotyping; Kinetics; Male; Mice; Mice, Nude; Neoplasm Transplantation; Orchiectomy; Ploidies; Prostate-Specific Antigen; Prostatic Neoplasms; Receptors, Androgen; Testosterone; Thymidine; Transplantation, Heterologous; Tumor Cells, Cultured

NK cell activity was measured in 24 patients with untreated prostate cancer (11 subjects with localized disease, D0, and 13 patients with stage D tumor) and 10 healthy controls. In these same subjects serum prostate-specific antigen (PSA), prostatic acid phosphatase (PAP), testosterone, prolactin and cortisol concentrations were assessed. The data obtained were correlated with both tumor spread (localized vs disseminated disease) and grade (well-differentiated cancer, G1, vs moderately and poorly differentiated carcinoma, G2 and G3). In patients with stage D0 cancer mean NK activity (33.0 +/- 10.6) was virtually identical with the mean value recorded in healthy men (34.5 +/- 7.1), while in subjects with stage D1-D2 disease NK activity was significantly reduced (11.9 +/- 7.1). These findings correspond with our data on treated subjects, in whom NK activity level was found to correlate well with the presence of tumor cells in the circulation. In subjects free of malignant tumors but with a chronic disease (diabetes, arthritis, severe rheumatic disorders) mean NK activity was clearly reduced (5.7 +/- 1.5). The use of NK activity data as a probe for tumor metastases was found to be statistically as reliable as was the application of the PSA serotest (but not serum PAP concentrations). None of the measured hormonal parameters correlated well with tumor stage. Both testosterone and prolactin serum concentrations were found to be lower in the G2 and G3 cancer group than in well-differentiated (G1) tumors, in accordance with the published literature.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acid Phosphatase; Aged; Biomarkers, Tumor; Hormones; Humans; Killer Cells, Natural; Male; Middle Aged; Neoplasm Staging; Prostate-Specific Antigen; Prostatic Neoplasms

To determine whether the prostate specific antigen (PSA) and prostatic acid phosphatase (PAP) immunoreactivities in prostatic carcinoma are reliable prognostic factors, the PSA and PAP immunohistochemical distribution was examined in needle biopsy specimens of 80 patients with advanced prostatic carcinoma. Our results indicated a higher cancer-specific survival rate in patients with a greater PSA or PAP immunostaining. Furthermore, a multivariate analysis of possible prognostic factors, that is patient age, clinical stage, Gleason score, serum PAP, PSA and PAP immunostaining scores, and the initial treatment, has confirmed that the difference in PAP immunoreactivity is the most important prognostic factor (p < 0.01) for advanced prostatic carcinoma, with the Gleason score (p = 0.06), clinical stage (p = 0.09) and PSA immunoreactivity (p = 0.48) being the second, third and fifth prognostic factors, respectively.

Topics: Acid Phosphatase; Age Factors; Aged; Aged, 80 and over; Humans; Immunohistochemistry; Male; Middle Aged; Multivariate Analysis; Prognosis; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Survival Rate

Lipofectin, the commercially available cationic liposome, was used to introduce the purified prostatic acid phosphatase protein into the established human prostate carcinoma cells. The incorporated phosphatase protein which retained its enzymatic activity as demonstrated by the tartrate-sensitive acid phosphatase assay was localized in the cytoplasm by immunofluorescence staining. Further, cells that were treated with phosphatase/Lipofectin complexes expressed a decreased phosphotyrosine level, presumably due to the endogenous protein tyrosine phosphatase activity of the acid phosphatase protein. A cationic liposome such as lipofectin may thus be employed to mediate transport of other acidic proteins into cells, providing a way to examine their biological functions in vivo.

Topics: Acid Phosphatase; Cations; Fluorescent Antibody Technique; Humans; Male; Phosphatidylethanolamines; Phosphotyrosine; Prostatic Neoplasms; Time Factors; Transfection; Tumor Cells, Cultured; Tyrosine

A histochemical study of 27 well-differentiated prostatic carcinoma cases associated with prostatic intra-epithelial neoplasia (PIN) was carried out. In the histological areas examined a decreasing production of neutral mucin was found as follows: normal prostatic tissue (70%), prostatic carcinoma (55%), PIN 1 (50%), PIN 2 (30%) and PIN 3 (15%). A progressively increasing content of acidic mucin (AB 2.5) was observed in the areas of PIN 3 (25%), PIN 2 (35%) and prostatic carcinoma (70%), while it was absent in the areas of PIN 1 and normal prostatic tissue. Acidic mucin sulphated type (AB 1) was secreted only in PIN 3 (5%) and prostatic carcinoma (10%) areas. These data were correlated with the proliferative activity of PIN. It is postulated that the lower neutral mucin production by PIN 3 can be linked to the higher proliferative activity of this lesion. Moreover, the acidic mucin secretion by PIN and prostatic carcinoma is considered to be a further feature of these lesions.

Topics: Acid Phosphatase; Histocytochemistry; Humans; Male; Mucins; Precancerous Conditions; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms

The tumor marker study attempts to make a diagnosis before the clinical diagnosis. We have studied some of these tumor markers (PSA, PAP and acid phosphatase) in 97 patients who suffered from benign prostatic hypertrophy, prostatic cancer and other non-prostatic pathologies. PSA appears to be the best marker, as reported in the literature. The sensitivity and specificity for two different cut off levels (5 and 10 ng/ml) were analyzed in order to determine the best. The statistical analysis was done by the chi-square method. The differences between the tumor markers were not significant for sensitivity. PSA appears to be more sensitive than PAP. Although there are no significant differences for sensitivity between both cut-off levels, and between PSA and PAP. We consider that the 10 ng/ml cut off is better assuming we will have a higher percentage of specificity (p < 0.05).

Topics: Acid Phosphatase; Adenocarcinoma; Aged; Aged, 80 and over; Humans; Male; Middle Aged; Prostate; Prostate-Specific Antigen; Prostatic Hyperplasia; Prostatic Neoplasms; ROC Curve

Topics: Acid Phosphatase; Humans; Male; Prostatic Hyperplasia; Prostatic Neoplasms; Tartrates

We describe a sampling method of obtaining fresh prostate cells that yields adequate numbers of cells for flow cytometric deoxyribonucleic acid (DNA) analysis and produces histograms of good resolution. Exfoliated cells from 204 prostate biopsy wash specimens obtained by agitation of biopsy cores in saline were fixed and stained for DNA analysis. The mean percentage of hyperdiploid cells was statistically different between the pathologically benign and malignant specimens (p < 0.0001). Hyperdiploid cells of 22% or more exhibited a high degree of specificity for the malignant specimens with only a 1.4% (1 of 69 benign specimens) false-positive rate. However, sensitivity was only 41% (25 of 59 malignant specimens were associated with a flow cytometry analysis of 22% or greater hyperdiploid cells) because of the high false-negative rate (59%, 35 of 59). The percentage of hyperdiploid cells correlated statistically with increasing prostate specific antigen (PSA) levels and approached significance with Gleason grade but did not correlate with prostatic acid phosphatase or clinical stage. When the amount of hyperdiploid cells was 22% or more and serum PSA level was greater than 4.0 ng./ml. a 95% chance of a malignant biopsy was predicted. This result was greater than that predicted by a PSA elevation alone. Only a 5% chance of a malignant biopsy was present for patients with less than 22% hyperdiploid cells and 4.0 ng./ml. or less serum PSA, a decrease over either method separately. This method of DNA assessment permits prospective categorization of tumors by ploidy without interfering with histological assessment. The prognostic importance of ploidy analysis awaits further clinical followup.

Topics: Acid Phosphatase; Biopsy, Needle; DNA, Neoplasm; Flow Cytometry; Humans; Male; Ploidies; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Sensitivity and Specificity

Twenty seven patients with endocrine therapy relapsed prostate cancer were studied by measuring their prostatic acid phosphatase (PAP), prostate specific antigen (PSA), gamma-semino-protein (gamma-Sm) and alkaline phosphatase (ALP) serially before change of the treatment, and tumor marker doubling time was calculated. The exponential increase in PAP, PSA and gamma-Sm was observed in all patients and ALP showed a similar pattern in some. The values of PAP doubling time were the same as those of PSA, but gamma-Sm doubling time was slightly longer than the former ones. Tumor marker doubling time correlated with survival after the increase in markers, and also with time between the start of endocrine therapy and the increase in markers. Patients who showed either NC or PR to chemotherapy had a longer tumor marker doubling time than those with PD. In cases showing progression of bone metastasis, patients with exponential increase in ALP showed worse prognosis when compared with those showing other patterns. From these results, it was demonstrated that determination of tumor marker doubling time in patients with endocrine therapy relapsed prostate cancer was a valuable method to measure rate of regrowth, and to assess the prognosis after relapse.

Topics: Acid Phosphatase; Alkaline Phosphatase; Antineoplastic Agents; Biomarkers, Tumor; Humans; Imidazoles; Imidazolidines; Male; Neoplasm Recurrence, Local; Prognosis; Prostate-Specific Antigen; Prostatic Neoplasms; Prostatic Secretory Proteins; Proteins; Seminal Plasma Proteins; Time Factors

Topics: Acid Phosphatase; Humans; Male; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms

The authors are reporting the clinical importance of prostate specific antigen. They concluded that there are false positive and false negative cases. The prostate specific antigen is high in prostatic hyperplasia therefore the distinction between the two disease is impossible on basis of the prostate specific antigen. Prostate specific antigen shows the metastatic cases better [correction of worse] than prostatic acid phosphatase. But prostate specific antigen detects the changes of the clinical course of the disease well and shows the progression sooner. The authors have concluded that prostate specific antigen can not replace phosphatases and bone-scanning in the diagnosis and follow up of patients with prostate carcinoma.

Topics: Acid Phosphatase; Adenoma; Carcinoma; Diagnosis, Differential; False Positive Reactions; Humans; Male; Prostate-Specific Antigen; Prostatic Hyperplasia; Prostatic Neoplasms

Prostatic carcinomas (PCs) may be divided into two distinct categories: latent PCs, found mostly at autopsy, and clinical cases, which present with signs and symptoms. These two categories correspond fairly well to histologic grading of PCs and immunoperoxidase staining for prostatic specific antigen (PSA). The objective of this study was to find quantitative and qualitative differences if any, of PSA in PCs, corresponding to Gleason's histologic grade. By radiometric assay of PSA in tissue cytosol, PCs especially those of high histologic grade, were found to have lower PSA concentrations than normal and glandular hyperplastic prostatic tissue. Western blotting of cytosol was performed to detect differences between immunoreactive PSA of PCs compared with noncancerous tissue using both polyclonal and monoclonal antibodies against PSA. Western blotting with anti-PSA revealed some different bands between cancerous and noncancerous cytosols. Western blotting of cancerous and noncancerous cytosols was also performed using anti-prostatic acid phosphatase and anti-beta micro-seminoprotein. Reduced PSA concentration and different immunoblotting pattern of PSA were found to be characteristic for PCs, especially in carcinomas with grades higher than 7, which usually present with more aggressive invasion and metastases.

Topics: Acid Phosphatase; Biomarkers; Blotting, Western; Humans; Male; Predictive Value of Tests; Prostate-Specific Antigen; Prostatic Neoplasms

The outcome of radiation therapy for localized prostate cancer depends on many pretreatment variables that are interrelated in complex ways. A multivariate analysis of 874 cases of prostate cancer treated between 1966 and 1988 was conducted. The median length of the follow-up period after radiation therapy was 6.7 years.. The disease outcome and rate of survival was analyzed with the proportional hazards model for patients with stage A2 (104), stage B (168), or stage C (602) prostate cancer treated with radiation therapy as the only primary treatment.. Local recurrence rates were 12%, 24%, and 33% at 5, 10, and 15 years, respectively. In multivariate analysis, stage (A2 vs. B+C) and pathologic grade (1 + 2 vs 3 + 4) were independently related to local recurrence. At 10 years local control had been achieved in 79% of favorable cases (stage A2 or stage B/C, grade 1), but in only 62% of unfavorable cases (stage B/C, grade 4). Metastatic relapse rates were 25%, 38%, and 47% at 5, 10, and 15 years, respectively. Factors that independently correlated with metastasis were high pathologic grade, transurethral resection in stage C, elevated acid phosphatase levels, and being 60 years of age or younger. A favorable group of cases (stage A2/B, grade 1 or stage C, grade 1, no transurethral resection, older than 60 years of age) had a metastatic rate of only 10% after 10 years, whereas an unfavorable group (largely stage C, grades 3/4) had a metastatic rate approaching 70%. The overall survival rate was 77%, 49%, and 32% at 5, 10, and 15 years, respectively. Pathologic grade (1 vs 2 + 3 vs 4) and transurethral resection in stage C correlated with survival. A favorable group of patients (stage A2/B or stage C and grade 1) had a normal survival expectation of 15 years. An unfavorable group consisting of grade 4 tumors had a survival rate of less than 20% at 10 years.. The complexity and long natural history of prostate cancer demand careful stratification and follow-up examination to evaluate treatment results. The study of adjuvants to improve the local effectiveness of radiation and to mitigate the high metastatic rates in unfavorable local disease are urgent priorities.

Topics: Acid Phosphatase; Adenocarcinoma; Adult; Aged; Aged, 80 and over; Combined Modality Therapy; Follow-Up Studies; Humans; Lymphatic Metastasis; Male; Middle Aged; Multivariate Analysis; Neoplasm Recurrence, Local; Neoplasm Staging; Prognosis; Prostate; Prostate-Specific Antigen; Prostatectomy; Prostatic Neoplasms; Radiotherapy, High-Energy; Retrospective Studies; Survival Rate; Treatment Outcome

Prostatic inhibin peptide (PIP), consisting of 94 amino-acid residues is synthesized and secreted by the prostate gland. Previous studies on immunohistochemical localization of PIP in primary prostatic tumor and their metastasis, have documented the value of this peptide as a tumor marker for diagnosis of prostate cancer (PCa). The present study was undertaken to compare the expression of PIP with that of prostate specific antigen (PSA) and prostatic acid phosphatase (PAP) in androgen independent human PCa cell lines (PC-3, DU-145 and TSU-Prl) by immunoperoxidase technique. The results of the study indicated that the staining for PIP was more intense than that of PSA and PAP. The PSA staining was either weakly positive (PC-3) or totally absent (TSU-Prl and DU-145) while PAP staining was intense in PC-3 and moderate in the other two human cell lines. The intense staining observed for PIP in all of the androgen independent cell lines suggests that the synthesis and secretion of PIP is not primarily dependent on androgens. Furthermore, expression of these markers in Dunning rat cultured adenocarcinoma cell lines and tumors were studied. Positive staining for all three human tumor associated antigens (PIP, PSA and PAP) cross-reacting with the Dunning rat PCa cell lines and the tumors, suggest the suitability of this model for preclinical screening of various therapeutic agents.

Topics: Acid Phosphatase; Adenocarcinoma; Animals; Biomarkers, Tumor; Cell Line; Cross Reactions; Humans; Immunoenzyme Techniques; Inhibins; Male; Peptide Biosynthesis; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Prostatic Secretory Proteins; Rats; Tumor Cells, Cultured

In this report we have investigated levels of prostatic acid phosphatase (PAP) and prostate-specific antigen (PSA) gene expression in prostatic carcinoma (Ca) and benign prostatic hyperplasia (BPH) specimens. Northern-blot analyses of total prostatic mRNA indicated that there was a tendency towards lower amounts of PAP mRNA and PSA mRNA in the Ca specimens than in the BPH specimens, although, because of the great variation in the expression levels of both mRNAs, these differences were not statistically significant. In situ hybridization analyses clearly showed that both PAP and PSA mRNAs were confined to the columnar epithelial cells and that stromal cells were devoid of these mRNAs. In addition, PAP and PSA mRNAs were more abundant in BPH tissue than in adjacent Ca tissue within the same specimen. The levels of PAP and PSA enzymes were analyzed immunohistochemically using a bispecific antibody having high affinity for both PAP and PSA, and the results were compared with those obtained using monoclonal anti-PAP and anti-PSA antibodies. All 3 antibodies stained only epithelial cells and BPH tissue consistently gave more intense staining than Ca tissue. Furthermore, the anti-PSA and the bispecific anti-PAP-PSA antibodies stained well or moderately differentiated Ca tissues more strongly than poorly differentiated Ca tissues. No PSA staining was detected in 3 and no PAP staining in 5 of the moderately or poorly differentiated carcinomas (grades II or III). Our results show that, in comparison with BPH tissue, prostatic Ca tissue is associated with significantly lower levels of mRNAs coding for the prostatic marker enzymes PAP and PSA, as well as with lower concentrations of these enzymes. Furthermore, dedifferentiation of prostate Ca is associated with a decrease in the level of intraprostatic PSA.

Topics: Acid Phosphatase; Adenocarcinoma; Antibodies, Bispecific; Antibodies, Monoclonal; Blotting, Northern; Gene Expression; Humans; Immunohistochemistry; In Situ Hybridization; Male; Prostate; Prostate-Specific Antigen; Prostatic Hyperplasia; Prostatic Neoplasms; RNA, Messenger

The value of prostatic acid phosphatase (PAP) and prostate specific antigen (PSA) as serum markers in carcinoma of the prostate (CaP) was investigated in this study. A group of 75 patients entered this trial, 25 with CaP, 25 with benign prostatic hyperplasia (BPH) and 25 with urologic disorders other than prostatic diseases. In the CaP group, PAP was above normal levels in 48% of the patients and PSA in 92%. In the BPH group these rates were 20% and 72%, respectively. No elevation was detected in the third group. In CaP patients with capsular invasion, PAP and PSA levels were above normal in 25 and 87.5%. In metastatic carcinoma, PAP was high in 75% and PSA in 100%. Our study reveals that neither of these markers is useful in the initial diagnosis of CaP. Though PSA seems to be more sensitive, it is not more specific than PAP.

Topics: Acid Phosphatase; Aged; Aged, 80 and over; Biomarkers, Tumor; Humans; Male; Middle Aged; Prostate; Prostate-Specific Antigen; Prostatic Hyperplasia; Prostatic Neoplasms; Urologic Diseases

Serum prostate secretory protein (PSP) levels were measured in 49 patients with benign prostatic hyperplasia (BPH), 144 patients with various stages of prostatic carcinoma (CaP), and 82 CaP patients who were followed serially. PSP values were compared with serum levels of prostate specific antigen (PSA) and prostatic acid phosphatase (PAP). In the BPH group, PSP was elevated (> 10 ng/ml) in 41% of patients, whereas PSA (> 4 ng/ml) and PAP (> 3.3 ng/ml) were elevated in 39% and 23% of the cases, respectively. PSP levels were elevated in 48% of the CaP pretreatment specimens, compared to 79% for PSA and 40% for PAP. PSP levels in cancer patients who had intracapsular disease were about two to three times higher than those observed for PAP. PSP was found to be the only marker elevated in eight (6%) pretreatment CaP patient serum specimens, while PAP was never found to be elevated when PSA was normal. PSP serum concentrations correlated with the clinical course of the disease in 79% of patients, compared with 90% for PSA and 66% for PAP. In certain patients, monitored over time, disease correlation was reflected in serum values with only a single biomarker, i.e., 1% with PAP, 8% with PSP, and 10% with PSA. This study has shown that PSP is a less sensitive serum biomarker than PSA, but more sensitive than PAP for detection and monitoring the early stages of prostate cancer. This suggests that PSP as a biomarker may be a useful adjunct for the management of a subpopulation of low-stage and -grade CaP.

Topics: Acid Phosphatase; Biomarkers; Carrier Proteins; Humans; Male; Predictive Value of Tests; Prostate; Prostate-Specific Antigen; Prostatic Hyperplasia; Prostatic Neoplasms; Prostatic Secretory Proteins; Sensitivity and Specificity

Several effects of androgens on LNCaP-FGC prostate tumor cells showed a biphasic pattern. Stimulation of growth and inhibition of secretion of prostatic acid phosphatase (PAP) was observed at low androgen concentrations (below 1 nM of the synthetic androgen R1881), and inhibition of growth and stimulation of PAP secretion was observed at higher concentrations. In contrast, prostate specific antigen (PSA) secretion did not show this biphasic response pattern. Comparable effects were found for two sublines of the LNCaP-FGC cells: an early (passage 20, androgen-dependent) and relatively late (passage 70, androgen-sensitive) passage of the cells. Culturing of both sublines in the presence of a high concentration of androgens (10 nM R1881) resulted initially in a decrease in growth rate, but the cells started to proliferate within 3 weeks. These cells became less sensitive to androgens, lost their biphasic response pattern, and showed reduced androgen receptor levels. Three weeks after removal of the excess of androgens, the passage 70 cells regained a biphasic growth response to androgens. Culture in medium without steroids but with EGF resulted in a decrease of both androgen sensitivity and androgen receptor level. In conclusion, rapid changes of the androgen sensitivity and receptor level of the LNCaP cells occurred under the influence of culture conditions. These changes were partly reversible and, therefore, were most likely due to adaptation of the cells.

Topics: Acid Phosphatase; Androgens; Cell Division; Culture Media; Humans; Male; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Receptors, Androgen; Tumor Cells, Cultured

Human prostatic acid phosphatase (PAcP) is a prostate epithelium-specific differentiation antigen and its expression has been proposed to be regulated by androgens. Since cellular PAcP may function as a protein tyrosine phosphatase, we investigated the regulatory mechanism of its expression at different growth stages in LNCaP cells, the only cultured human prostate carcinoma cells that express an endogenous PAcP. Cells were plated at different densities to represent different stages of cellular growth for quantitating the expression of PAcP. In 4-d subconfluent cells, the cellular PAcP activity and protein level increased following the seeded cell density, consistent with mRNA levels. By day 7, all cultures had an approximately equal amount of total cellular proteins, indicating that cell growth approached to confluence, except the one that was plated at the lowest density. The cellular PAcP activity per cell was increased and corresponded to its protein level as observed in 4-d cultures. However, in 7-d cultured cells, although the PAcP protein level increased, its mRNA level declined. This increased PAcP protein level despite the decreased message was in part due to a prolonged half-life of the protein. Further, androgen effect on the PAcP mRNA level was also shown to be a cell density-dependent phenomenon. In low-density cultured cells, the PAcP mRNA level was elevated approximately 100% by 5 alpha-dihydrotestosterone (DHT) stimulation. However, in high-density confluent cells the mRNA level was slightly decreased by DHT treatment. Further, treatments with various growth stimulators resulted in various degrees of inhibition on PAcP mRNA levels. In conclusion, the data indicate that the cellular level of PAcP activity is associated with the cell density/confluence of LNCaP cells. Further, cell density could modulate androgen effect on PAcP expression at the mRNA level.

Topics: Acid Phosphatase; Biomarkers, Tumor; Cell Count; Cell Division; Dihydrotestosterone; Gene Expression Regulation, Neoplastic; Half-Life; Humans; Male; Prostate; Prostatic Neoplasms; RNA, Messenger; Tumor Cells, Cultured

Quantitative bone scintigraphy was performed in 24 patients with prostatic carcinoma before orchiectomy and up to one to four years after operation. The gamma camera count rate was recorded over the lower thoracic and all lumbar vertebrae 4 h after injection of 99mTc-MDP. Twelve patients had normal bone scintigrams throughout the study. They showed from two years after operation a slight increase in count rate values compared with the preoperative values, probably due to hormonal changes after orchiectomy and to age-related alterations in skeletal metabolism. Twelve patients had abnormal bone scintigrams. They showed as a response to treatment the flare phenomenon with an increase in count rate over the abnormal vertebrae when measured two weeks after operation followed by a decrease after two months. The lowest count rate values were obtained between six months and one year after operation. Thereafter the count rate seemed to remain on the same level. An increase in count rate was connected to progression of disease and the patients died of prostatic carcinoma within one year thereafter.

Topics: Acid Phosphatase; Aged; Aged, 80 and over; Alkaline Phosphatase; Bone Neoplasms; Humans; Male; Orchiectomy; Prostatic Neoplasms; Radionuclide Imaging; Technetium Tc 99m Medronate; Treatment Outcome

Human prostatic acid phosphatase (ACPP) has been used as a diagnostic marker for prostate cancer. It is synthesized under androgen regulation and secreted by the epithelial cells of the prostate gland. We have confirmed the previous assignment of the ACPP gene to chromosome 3 by probing a panel of 25 human-Chinese hamster somatic cell hybrids, and we have further localized the ACPP gene to chromosome 3q21-q23 by fluorescence in situ hybridization.

Topics: Acid Phosphatase; Animals; Chromosome Banding; Chromosome Mapping; Chromosomes, Human, Pair 3; Cricetinae; DNA, Complementary; Genetic Markers; Humans; Hybrid Cells; In Situ Hybridization, Fluorescence; Male; Prostate; Prostatic Neoplasms

Since 1981 we have been studying prostate cancer (Pca) by mass screening (MS) in the Gunma Prefecture, Japan. From 1981 to 1990, 9,067 subjects (total 15,451) were examined in connection with this project and 121 subjects were diagnosed as having Pca. The presence of Pca in 87 cases was confirmed at their initial MS (initial group); 34 cases were confirmed either the year after or several years after the first MS (repeat group). To evaluate the significance of MS for Pca, in this group of patients, the effects of 'lead time bias', 'self-selection bias' and 'length bias' on the survival rate were compared to Pca patients detected in the hospitals of the Gunma Prefecture during the same period. The survival curves of MS cases for each stage of the disease were better than those of the controls. Only in stage D was there a significant difference between the two groups. However, this MS curve decreased from the 4th year in the same manner as the control curve from the start. The clinical characteristics (age, pathological differentiation, prostatic acid phosphatase, gait disturbance, erythrocyte sedimentation rate, chronic disease, and pain in the patients with stage D disease) were compared between both groups. All characteristics studied, except age, in the MS group were clinically more favorable compared to those of the controls for each stage or in total. Moreover, the relative survival rate of subjects examined by MS was greater than 1.0. No significant difference was found in stage distribution between the initial group and the repeat group.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acid Phosphatase; Age Factors; Aged; Aged, 80 and over; Bias; Blood Sedimentation; Follow-Up Studies; Humans; Japan; Male; Mass Screening; Middle Aged; Neoplasm Staging; Pilot Projects; Prostatic Neoplasms; Selection Bias; Survival Rate; Time Factors

From a prospective database of 614 consecutive men with newly diagnosed prostatic cancer an audit of outcome was studied in 169 men who presented with bone metastases and subsequently received hormonal manipulation in the form of monotherapy. The cohort was divided into 2 groups according to serum alkaline and acid phosphatase enzyme levels. Men with normal alkaline phosphatase levels (41.5%) had a better prognosis (median survival 38 months) than those with elevated levels at presentation (58.5%) (median survival 19 months). This difference was highly significant. A similar stratification on prostatic acid phosphatase levels did not yield any prognostic significance. With regard to cause-specific survival, serum alkaline phosphatase was an even more powerful prognosticator, with a median survival of 45 and 21 months for patients with normal and elevated levels respectively. Thus monotherapy is recommended for metastatic prostate cancer patients with normal serum alkaline phosphatase, but for those with elevated alkaline phosphatase the alternative avenues of treatment must be explored.

Topics: Acid Phosphatase; Aged; Alkaline Phosphatase; Biomarkers, Tumor; Bone Neoplasms; Follow-Up Studies; Humans; Male; Orchiectomy; Prognosis; Prospective Studies; Prostatic Neoplasms; Treatment Outcome

Eighty-two patients with advanced prostatic carcinoma were treated with a long-acting luteinizing hormone releasing hormone (LHRH) agonist (Zoladex depot, Zeneca Pharmaceuticals, England). The outcome of the treatment was monitored on the basis of the following prognostic factors: local stage, number of bone metastases, histological differentiation grade and prostate-specific acid phosphatase (PAP), alkaline phosphatase (AF) and testosterone levels. The patients were followed-up until disease progression or until death. The mean weight of the prostate decreased from 48.1 g to 17.4 g (P < 0.00001) during the first year of treatment. Statistically there was a significant difference in regard to appearance of progression between different clinical stages (P < 0.00001). The prognosis was poorest in patients with more than 10 metastases at the primary stage. If the PAP level was initially higher (over 20 micrograms/L), the prognosis was very poor. Statistically there was a significant difference between the high PAP level and the slightly elevated or normal PAP (P < 0.02 and P < 0.005, respectively). Alkaline phosphatase (AF) appeared to be a good prognostic factor. The prognosis was particularly poor, if the AF level exceeded 1000 U/L (P < 0.00001 and P < 0.05, compared with normal AP and slightly elevated AP level, respectively). Surprisingly, a high pre-treatment testosterone level worsened the prognosis during the LHRH agonist treatment (P < 0.01, compared to patients with normal testosterone level). This is a new finding and controversial to the findings reported before.

Topics: Acid Phosphatase; Aged; Alkaline Phosphatase; Bone Neoplasms; Follow-Up Studies; Goserelin; Humans; Life Tables; Male; Neoplasm Staging; Prognosis; Prostate; Prostatic Neoplasms; Testosterone; Time Factors; Treatment Outcome

Purified human prostate acid phosphatase (PAP) was used to generate a specific monoclonal antibody (FC 3001) for detection of PAP expressed by some prostatic carcinomas. DTPA derivatives of MoAb-F(ab')2-fragments were labeled with indium-111 chloride. This labeled antibody was tested in 15 prostate cancer patients who underwent staging pelvic lymphadenectomy; 9 of them received labeled antibody alone whereas 6 received simultaneous injections of labeled and unlabeled antibody with two dose levels (40 or 80 mg). Biodistribution data obtained by direct blood measurements and imaging procedures indicated that simultaneous injection of unlabeled antibody reduced both the blood elimination rate and the accumulation in the liver. Accumulation of the radionuclide in pelvic lymph node metastases was observed in some patients but in a couple of patients accumulation was noted also in normal lymph nodes. The method cannot in its present design replace staging pelvic lymphadenectomy and further studies are needed for elaboration of clinically useful radioimmunodetection methods.

Topics: Acid Phosphatase; Antibodies, Monoclonal; Humans; Indium Radioisotopes; Male; Neoplasm Metastasis; Prostate; Prostatic Neoplasms; Radioimmunodetection; Tissue Distribution

The expression and the secretion of human prostatic acid phosphatase (PAcP), a differentiation antigen which is the major acid phosphatase in prostate epithelial cells, are thought to be regulated by an androgen. We investigated this regulatory mechanism at the post-transcriptional level in LNCaP human prostate carcinoma cells using a cDNA clone for the secretory form of PAcP. 5 alpha-Dihydrotestosterone (DHT, an active form of endogenous androgen) stimulated the secretion of PAcP from cells grown in a steroid-reduced medium and in a defined serum-free medium, respectively. The secreted PAcP activity was increased following a DHT dose in a dose-dependent fashion at concentrations of up to 1 microM. Further, the stimulation of PAcP secretion occurred following the period of exposure to DHT. During a 5-day treatment period, with 10 nM of DHT in the steroid-reduced medium, the secretion of PAcP was stimulated approximately 150% over that from control cells. Nevertheless, PAcP was secreted from cells grown in the absence of added DHT. First, the androgen dependency of PAcP expression was examined. The expression and the secretion of PAcP were observed in cells that were grown in a defined serum-free medium and grown in a steroid-reduced medium, in the absence of DHT. The increased secretion by DHT was further demonstrated to be in part due to an increase in PAcP mRNA level, as evidenced by Northern blot analysis. PAcP mRNA levels were elevated approximately 2-fold and corresponded to an increase of approximately 2.5-fold in the secreted level of newly synthesized 35S-PAcP. Then, the effect of DHT on the secretory process was investigated. Results of pulse-chase labeling experiments indicated that the secretory rate of PAcP was stimulated by about 50% on average by DHT. In conclusion, our data demonstrated that, in LNCaP cells, the expression and the secretion of PAcP regulated by androgen are apparently hormone-responsive processes. Further, DHT stimulation of PAcP secretion operates within at least two levels: increased PAcP mRNA and stimulation of the secretory pathway.

Topics: Acid Phosphatase; Blotting, Northern; Cloning, Molecular; Dihydrotestosterone; DNA Probes; Humans; Isoenzymes; Kinetics; Male; Methionine; Prostate; Prostatic Neoplasms; Restriction Mapping; RNA, Messenger; RNA, Neoplasm; Time Factors; Tumor Cells, Cultured

We investigated the prognostic factors in 138 patients with stage D2 prostatic cancer by univariate and multivariate analyses. Analysis was restricted to 8 pre-treatment parameters, that is, age, general condition (PS), pain, number of metastases on bone scan, acid phosphatase value, Gleason's primary pattern, secondary pattern, and nucleoli grading. In addition, 4 therapeutic modalities except routine endocrine therapy, that is, castration, oral administration of estramustine phosphate, of 5-fluorouracil (5-FU) or its analogue, and combination chemotherapy, during the whole treatment period were included in the analysis. Univariate analysis (Kaplan-Meier method) showed only PS to be a significant prognostic factor. Multivariate analysis (Cox's proportional hazard model) revealed that PS, Gleason's primary pattern, oral administration of 5-FU or its analogue and combination chemotherapy were significant prognostic factors. However, patients treated by combination chemotherapy had poorer prognosis and chi 2 values of combination chemotherapy was the highest among the four parameters cited above. These results suggested that the 8 pre-treatment parameters examined in this study were not sufficient for predicting the prognosis of each patient.

Topics: Acid Phosphatase; Aged; Analysis of Variance; Humans; Male; Neoplasm Staging; Prognosis; Proportional Hazards Models; Prostatic Neoplasms

Between 1981 to 1991, 126 patients were diagnosed with prostatic cancer from histological reports. Stage D2 prostatic cancer was confirmed in 38 of these cases at the time of the initial diagnosis (group alpha). Of 38 patients in group alpha, 13 had recurrence of disease after a good response to the initial treatment, 19 had no recurrence after the treatment and the other 6 patients showed no response to the initial treatment for prostatic cancer. Seven patients showed progression of the disease to stage D2 during the observation period (group beta). These forty-five patients with stage D2 prostatic cancer were analyzed. Poorly differentiated adenocarcinoma was the most frequently observed histological grade, followed by moderately differentiated. The grade of the extent of the disease (EOD) on bone scan was classified as EOD I in 26, EOD II in 13 and EOD III in 4, with no significant differences in the survival rate found among these groups. The sensitivity rate of prostate specific antigen was higher than that of other serum tumor markers. Twenty-three patients died during the observation period. 18 of the 23 died of prostatic cancer.

Topics: Acid Phosphatase; Adenocarcinoma; Aged; Aged, 80 and over; Biomarkers, Tumor; Bone Neoplasms; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Prostatic Neoplasms; Radionuclide Imaging; Survival Rate

With the development of reliable assays for the measurement of prostate specific antigen (PSA), the use of serum enzymatic acid phosphatase in the staging of disease before radical prostatectomy has been called into question. We evaluated 460 consecutive men who were referred to our institution as candidates for radical prostatectomy. Staging evaluation included digital rectal examination, serum measurements of enzymatic acid phosphatase and PSA, bone scans and, in patients in whom advanced clinical stage was anticipated, computerized tomography, magnetic resonance imaging or transrectal ultrasonography. Of the 460 men 21 (4.6%) had elevations of serum enzymatic acid phosphatase. All 19 men with elevations who were fully evaluated proved to have either positive bone scans, extraprostatic extension of disease, PSA greater than 100 ng./ml., positive lymph nodes or positive seminal vesicles. However, in 17 of the 21 men (81%) with elevated serum enzymatic acid phosphatase advanced disease was detected by either abnormal digital rectal examination or PSA alone. Thus, serum enzymatic acid phosphatase provided unique information in only 4 of the entire study population (0.9%). Recognizing this low yield of unique information, we believe that measurements of serum enzymatic acid phosphatase are no longer mandatory before radical prostatectomy but may provide important confirmatory information in patients in whom advanced disease is suspected.

Topics: Acid Phosphatase; Adult; Aged; Biomarkers, Tumor; Humans; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Staging; Preoperative Care; Prostate-Specific Antigen; Prostatectomy; Prostatic Neoplasms

To assess the efficacy of serum prostate specific antigen (PSA) in the diagnosis of prostatic cancer. To compare this tumour marker with serum acid phosphatase (ACP) in order to define the more effective diagnostic test.. Serum samples from 349 patients attending a urology department were assayed for PSA and ACP. Histological assessment of prostatic biopsy samples was used as the standard by which the diagnostic effectiveness of the tumour markers was determined.. Mean serum PSA results from patients with prostatic carcinoma (159 (SEM 35) ng/mL) were significantly different to those from patients with benign prostatic hyperplasia (4.0 (0.53) ng/mL). As there was considerable overlap of results, test sensitivities and specificities were calculated for various decision points. The sensitivity and specificity of PSA at a level of 10 ng/mL were 61.2% and 93.0% respectively, while for ACP at a level of 0.8 U/L they were 47.6% and 89.9%. The areas beneath receiver-operator curves (0.81 for PSA and 0.72 for ACP) indicated that PSA gives better diagnostic information than ACP. For a stated incidence of cancer, posttest probabilities following a given PSA result have been calculated.. PSA is a more effective serum marker for prostatic carcinoma than ACP. We present a table so that for similar patient groups posttest probabilities for prostatic cancer can be assessed for a given serum PSA level.

Topics: Acid Phosphatase; Analysis of Variance; Biomarkers, Tumor; Clinical Enzyme Tests; Humans; Male; Predictive Value of Tests; Prostate-Specific Antigen; Prostatic Neoplasms; ROC Curve; Sensitivity and Specificity

Thirteen cases are reported with normal levels of prostate-specific antigen and elevated prostatic acid phosphatase (PAP). Conditions that were associated with an elevated PAP were myeloproliferative syndromes (four cases), metastatic nonprostatic carcinoma (six cases), prostatic carcinoma (one case), tuberculosis with a concurrent lupus-like syndrome (one case), and osteomyelitis (one case). The inclusion of PAP in the initial investigation of cases with suspected prostatic disease results in a decreased specificity.

Topics: Acid Phosphatase; Aged; Aged, 80 and over; Biomarkers, Tumor; Humans; Male; Mass Screening; Prostate-Specific Antigen; Prostatic Neoplasms; Reference Values

Serum values of prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP) were determined in 180 patients prior to pelvic lymphadenectomy and radical prostatectomy and in 40 patients prior to pelvic lymphadenectomy alone. In all tumor stages, PSA was superior to PAP in detecting cancer of the prostate. By PSA determination using a cutoff level of 4 ng/ml (Tandem assay), 28.8% of the patients with prostate cancer, stage pT2pN0M0, and 17.8% of the cases with a stage pT3pN0M0 tumor could not be detected. All these tumors had been noticed, however, by digital rectal examination. This indicates that PSA determination cannot replace digital rectal examination as a screening method for prostate cancer. In this study, it was possible neither by PSA nor by PAP to define a practicable cutoff level for patients with and without lymph node metastases. A clear differentiation between the stages pT2pN0M0 and pT3pN0M0 was not possible by either PSA or PAP alone.

Topics: Acid Phosphatase; Biomarkers, Tumor; Humans; Lymphatic Metastasis; Male; Neoplasm Staging; Predictive Value of Tests; Prospective Studies; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms

Correlations between the serum levels of PAP and PSA before and 1, 3 and 6 months after orchidectomy in 27 prostatic cancer patients (advanced clinical stages C and D according to Whitemore scale) were studied. The PSA values correlated more distinctly than PAP with the general clinical condition. PSA is a reliable tumour marker when used at regular intervals, especially for monitoring therapeutic results. A high preoperative PSA level correlates with a high postoperative level and progression of the disease.

Topics: Acid Phosphatase; Aged; Aged, 80 and over; Biomarkers, Tumor; Clinical Enzyme Tests; Humans; Male; Middle Aged; Orchiectomy; Prognosis; Prostate-Specific Antigen; Prostatic Neoplasms; Remission Induction

The usefulness of prostatic specific antigen (PA) was compared with that of prostatic acid phosphatase (PAP). PA was determined in the serum of 2,183 patient examined by the mass screening for prostate cancer from 1987 to 1990. The serum samples of these patients were obtained from our serum bank. PA was measured by the E test "TOSOH" II (PA). The relationship of PA and PAP to prostate size estimated by digital rectal examination (DRE) and ultrasound tomography (US), and age was investigated. PA and PAP correlated with aging and prostate size estimated by DRE. However PA was more apparently related with these things. The correlation between PA and prostatic size estimated by US was relatively high (r = 0.53), but the correlation between PAP and prostate size estimated by US was low (r = 0.20). When the upper limit of normal range was set at 6.0 ng/ml, the sensitivity, specificity and efficiency was 64%, 97% and 62%, respectively. PA was more sensitive than PAP and could be more useful since none of the patients with prostate cancer was PAP positive and PA negative. We conclude that PA should be a reliable tumor marker in our mass screening system.

Topics: Acid Phosphatase; Adult; Age Factors; Aged; Aged, 80 and over; Biomarkers, Tumor; Humans; Male; Mass Screening; Middle Aged; Prostate-Specific Antigen; Prostatic Neoplasms; Ultrasonography

Analysis of the clinical progression of 61 patients with prostate cancer undergoing hormone therapy. PSA allowed early detection in 86.9% cases. In 25 patients no rescue treatment was instituted, and 36 patients were treated with estramustine phosphate resulting in decreased PSA levels in 58% and objective response in 36%. Of these, 82% showed decreased PSA levels for over six months. Survival rate was higher in respondent, treated patients and comparable in non-respondents, treated versus non treated patients.

Topics: Acid Phosphatase; Actuarial Analysis; Androgen Antagonists; Biomarkers, Tumor; Diethylstilbestrol; Estramustine; Humans; Male; Orchiectomy; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Retrospective Studies; Survival Analysis; Treatment Outcome

The diagnostic value of the tumour markers: PSA, PAP and AcP was studied before treatment in 379 men (47 with prostatic cancer--PC, 306 with benign hyperplasia--PBH, and 26 healthy subjects--control group CG). PSA was determined by the enzymoimmune method, and the phosphatases were evaluated by the spectrophotometric method. Raised level of PSA was found in PBH--the highest value--23.3 ng/ml. After accepting the cutting off values (1.9 ng/ml and 23.3 ng/ml), even in 93% of patients with PC, the level of PSA exceeded the second of those values. A significant growing tendency was found of PSA together with the degree of clinical progression of PC (in stages C and D--in 100% of patients). PSA, as compared with the phosphatases, is a much more sensitive biochemical marker, exceeding them many times in sensitivity.

Topics: Acid Phosphatase; Adenoma; Aged; Aged, 80 and over; Biomarkers, Tumor; Humans; Male; Middle Aged; Prostate-Specific Antigen; Prostatic Neoplasms; Sensitivity and Specificity

To evaluate a relationship between Gleason scores of histopathology of prostate carcinoma and concurrent serum prostate-specific antigen (PSA) and prostate acid phosphatase (PAP) values, 65 men with prostate carcinoma were studied. These patients' cumulative Gleason scores were obtained by totaling the primary and secondary patterns, resulting in two groups: 42 patients received high (6-10) and 23 received low (2-5) Gleason scores. Serum PSA and PAP values were measured by radioimmunometric assay 1 to 7 days before surgical procedures or biopsy for prostate carcinoma. Mean serum PSA for patients in the high Gleason score group was 134.39 ng/mL (normal range: 0 to 4), and the mean serum PSA for patients in the low Gleason score group was 23.62 ng/mL. Mean serum PAP for patients with high scores was 28.08 ng/mL (normal range: 0 to 5), and the mean serum PAP for patients with low scores was 18.19 ng/mL. Patients with high Gleason scores showed significantly greater elevation of serum PSA than those with low Gleason scores (P = .047), using two samples to test for groups having unequal variants. Prostate acid phosphatase levels of patients with high scores were not significantly higher than the levels in patients with low scores (P = .60). These results indicate that PSA levels but not PAP levels correlate with Gleason scores.

Topics: Acid Phosphatase; Adenocarcinoma; Aged; Aged, 80 and over; Biomarkers, Tumor; Humans; Male; Middle Aged; Prostate-Specific Antigen; Prostatic Neoplasms

We studied the influence of prostatic massage on the seric levels of acid prostatic phosphatase (PAP) and prostatic specific antigen (PSA) before and 1, 24 and 48 h after the examination. Three groups of patients were studied: 13 patients with prostatic benign hypertrophy (PBH), six patients with metastatic prostate carcinoma and 10 control patients (urinary lithiasis). We observed a significant elevation of both seric markers 1 h after prostatic massage in the PBH and control groups. In both groups, seric marker levels returned to normal values within 24 h with PAP and 48 h with PSA. We recommend to assay serum PSA and PAP with an interval of at least 48 h after rectal digital examination.

Topics: Acid Phosphatase; Adult; Aged; Humans; Male; Massage; Middle Aged; Prostate; Prostate-Specific Antigen; Prostatic Hyperplasia; Prostatic Neoplasms

Prostate cancer is a disease mostly effecting aged men. The incidence rate of this disease is much lower in China than in Europe and America. However, certain data have been accumulated indicating an increasing tendency in this country in recent years. The present report also supports this view and suggest the importance of strengthening of epidemiological research in this area in future. The problem how to treat patients with advanced prostate cancer is of essential importance since most cases are diagnosed in III or IV stage of the disease. In the present study, 10 out of 26 suspected cases (38.5%) was diagnosed by needle aspiration biopsy, being 90.9% of 11 cases confirmed histopathologically. The elevation of tumor maker acid phosphatase activity was positive in 8 out of 17 cases (47.1%). In this group, 11/17 (64.7%) received bilateral orchidectomy plus estrogenic hormones. The effective rate was 81.9% (9/11). Relapse occurred in 4 out of the 9 cases (44.4%), probably due to estrogenic hormone-dependence.

Topics: Acid Phosphatase; Adenocarcinoma; Aged; Aged, 80 and over; Biomarkers, Tumor; Biopsy, Needle; Combined Modality Therapy; Estrogens; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Orchiectomy; Prostatic Neoplasms

Topics: Acid Phosphatase; Adenocarcinoma, Mucinous; Humans; Male; Neoplasm Invasiveness; Prostatic Neoplasms

Paneth cell-like change (PCLC) of the prostatic glandular epithelium was focally observed in one case of normal glandular epithelium, two cases of glandular and stromal hyperplasia, one case of prostatic intraepithelial neoplasia, and four cases of prostatic adenocarcinoma. The distinctive cells were characterized by bright, eosinophilic cytoplasmic granules on routine hematoxylin and eosin-stained material. The cytoplasmic granules in the benign prostatic epithelium were periodate-Schiff's procedure (PAS)-positive and diastase resistant and immunohistochemically negative for lysozyme, neuron-specific enolase, chromogranin, and serotonin. The eosinophilic granules in the prostatic intraepithelial neoplasia and adenocarcinoma cases were immunohistochemically positive for chromogranin, serotonin, and neuron-specific enolase, and negative for lysozyme. By electron microscopy the eosinophilic granules represented exocrine-like or lysosomal-like vesicles in the benign epithelium and neuro-endocrine granules in the malignant epithelium. The lesion represents a prostatic epithelial PCLC rather than a Paneth cell metaplasia. PCLC is the common histological manifestation of two different phenomena: (a) a PAS-positive and diastase-resistant eosinophilic cytoplasmic granular change in benign prostatic epithelium, and (b) endocrine differentiation with neuroendocrine granules in dysplastic and malignant prostatic epithelia. The importance of recognizing PCLC lies in its differentiation from other possible prostatic cytoplasmic inclusions.

Topics: Acid Phosphatase; Adenocarcinoma; Aged; alpha 1-Antichymotrypsin; Antigens, Neoplasm; Carcinoma in Situ; Cell Transformation, Neoplastic; Chromogranins; Cytoplasmic Granules; Epithelium; Humans; Immunohistochemistry; Male; Microscopy, Electron; Middle Aged; Muramidase; Phosphopyruvate Hydratase; Prostate; Prostate-Specific Antigen; Prostatic Hyperplasia; Prostatic Neoplasms; Serotonin

To better understand androgen-regulated gene expression in the prostate, we have used Northern blot analysis to study the effects of androgens and other steroid hormones on the steady state levels of several human prostatic mRNAs in the LNCaP cell line. Dihydrotestosterone (40 nM) as well as a synthetic androgen, R1881 (0.1 nM), increased the amounts of prostate-specific antigen (PSA) and human glandular kallikrein mRNAs; at the same time, the level of prostatic acid phosphatase (PAP) mRNA was down-regulated. Incubation of LNCaP cells with medium containing 0.1 or 1 microM R1881 for 3, 7, or 13 days resulted in up-regulation of PSA and human glandular kallikrein mRNAs and down-regulation of PAP mRNA. Thus, the two clinically important prostate-specific marker proteins are inversely regulated in this cell line. The level of human androgen receptor mRNA was also repressed by the androgen treatments. 17 beta-Estradiol and progesterone had effects similar to those of R1881 on gene expression in LNCaP cells. Our results show that the decrease in the amount of secreted PAP and the increase in the amount of secreted PSA caused by androgens and other steroid hormones in the LNCaP cells of epithelial origin are mediated by changes in the levels of the corresponding mRNAs.

Topics: Acid Phosphatase; Actins; Androgens; Antigens, Neoplasm; Base Sequence; Cell Line; Dihydrotestosterone; Estradiol; Gene Expression Regulation, Enzymologic; Gene Expression Regulation, Neoplastic; Humans; Kallikreins; Male; Metribolone; Molecular Sequence Data; Oligonucleotide Probes; Progesterone; Prostate-Specific Antigen; Prostatic Neoplasms; RNA, Messenger; RNA, Neoplasm; Tissue Kallikreins

Prostate-specific antigen is a specific immunohistochemical marker of benign prostatic epithelium and prostate cancer. A subpopulation of neuroendocrine cells seen in 50% of cancers do not produce this protein marker. These cells appear to secrete prostate-specific acid phosphatase. This finding may explain the marked variation in serum prostate-specific antigen levels in all stages of prostate cancer.

Topics: Acid Phosphatase; Antigens, Neoplasm; Biomarkers, Tumor; Carcinoma; Chromogranin A; Chromogranins; Humans; Immunohistochemistry; Male; Neurosecretory Systems; Prostate-Specific Antigen; Prostatic Neoplasms; Staining and Labeling

The activity concentration and the specific activity (the ratio of enzyme activity to total serum protein) of the tartrate-inhibitable fraction of acid phosphatase [orthophosphoric monoester phosphohydrolase (acid optimum), EC 3.1.3.2; TIAP] were related to benign prostatic hypertrophy and to prostatic carcinoma. As expected, the TIAP activity concentrations assayed in the sera of patients with benign prostatic hypertrophy were within the range of those assayed in normal human sera. In contrast, the specific activities of TIAP determined in the sera of patients with benign prostatic hypertrophy were significantly higher than those determined in the control group. In the sera of prostatic carcinoma patients, both the TIAP activity concentrations and the TIAP specific activities differed significantly (F = 730) from the normal values.

Topics: Acid Phosphatase; Aged; Blood Proteins; Humans; Male; Middle Aged; Prostatic Hyperplasia; Prostatic Neoplasms; Reference Values; Tartrates

Adenocarcinoma associated antigen (ACAA) is a large molecular weight protein that is normally found in low serum levels. Recent data have revealed elevations in patients with adenocarcinomas, including prostate cancer. To evaluate the relationship of ACAA levels with prostate cancer, we measured the cytosol content in malignant and nonmalignant prostate tissue and compared these results to those of the standard markers, prostatic acid phosphatase (PAP) and prostatic specific antigen (PSA). Enzyme solid phase immunoassay was used to quantitate PSA and ACAA levels, and the enzymatic method was used to measure PAP. Wedge resection from the right and left posterior lobes of 50 fresh radical retropubic prostatectomy specimens were used for cytosol analysis. All foci of within each prostate gland were carefully mapped by a single pathologist. When all malignant wedges (N = 74) were compared to all the benign wedges (N = 21), only the PSA levels showed significant elevation (p less than 0.02). However, when benign and malignant tissue from the same prostate were available for comparison, both PSA (N = 17) and ACAA (N = 16) showed significant elevations in the cytosol of the malignant tissue (p less than 0.002 and p less than 0.03, respectively). Although not statistically significant, the cytosol PAP did show a consistent trend to be greater in malignant tissue. It appears that there is an association of increased cytosol ACAA and PSA with prostate cancer.

Topics: Acid Phosphatase; Adenocarcinoma; Antigens, Neoplasm; Biomarkers, Tumor; Cytosol; Humans; Male; Prostate-Specific Antigen; Prostatic Neoplasms

In order to elucidate the mechanism of androgen-regulation of genes expressed only in the prostate gland, the effects of steroid hormones on the biosynthesis and secretion of human prostatic acid phosphatase (PAP) and prostate-specific antigen (PSA) were studied in the human prostatic carcinoma cell line, LNCaP. This cell line produces PAP and PSA, both of which were found to be similar to the proteins purified from and located in human prostatic tissue, as shown by Western blot analysis. The synthetic androgen, R1881, regulated the biosynthesis of these two important tumour marker proteins inversely: the amount of PSA released into the medium was increased to 506% +/- 100 of the control levels, while that of PAP was decreased to 26% +/- 3, in 7 days. These effects were dependent on the concentration of the steroid in the growth medium. The androgen-dependent changes observed in the amounts of the secreted proteins were correlated with alterations in their intra-cellular levels. LNCaP cells were found to have very different capacities for secreting PAP and PSA. Whereas the measurable, cellular amounts of PSA and PAP were of similar magnitudes, much larger amounts of PSA than PAP were secreted into the medium. PSA was also found to be more stable than PAP in the culture medium of the LNCaP cells. Other steroids could elicit effects on PAP and PSA biosynthesis similar to those induced by R1881, and the combined effects of effective concentrations of these steroids were undistinguishable from those caused by each one of them separately, suggesting that all these compounds compete for binding to the same modified androgen receptors of the LNCaP cells. Thus, our results confirm the observations of the altered nature of the LNCaP androgen receptors, and demonstrate the ability of these ligands to produce changes in the expression of androgen-dependent prostatic genes. The fact that the changes observed at the protein level were accompanied by increased levels of PSA mRNAs and by decreased levels of PAP mRNA in steroid-treated cells, suggests that one of the targets of androgen and steroid action in the regulation of these genes is at the mRNA level.

Topics: Acid Phosphatase; Antigens, Neoplasm; Biomarkers, Tumor; Cell Line; Cycloheximide; Estradiol; Humans; Kinetics; Male; Metribolone; Pregnenediones; Progesterone; Progesterone Congeners; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; RNA, Messenger; Tumor Cells, Cultured

Tumor markers are antigens which can be associated with certain malignancies. A variety of markers have been demonstrated in genitourinary tumors. The best known examples are human chorionic gonadotropin (bHCG) and alpha-fetoprotein (AFP) for testicular tumors, prostatic acid phosphatase (PAP) and prostatic specific antigen (PSA) for prostatic cancer. The plasma levels of these substances are influenced by the tumor mass and therefore by the tumor stage. Markedly elevated plasma levels can be demonstrated when metastases are present, although a few patients without metastases may elaborate abnormal amount of markers. The removal of the primary tumor leads to a fall to normal levels: a still increased level indicates residual primary tumor or the presence of metastases. Measurements of markers are also of value in estimating the effects of medical treatment and in detecting local or distant recurrences.

Topics: Acid Phosphatase; alpha-Fetoproteins; Antigens, Neoplasm; Biomarkers, Tumor; Chorionic Gonadotropin; Humans; Male; Neoplasm Metastasis; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Testicular Neoplasms

Serum concentrations of prostatic acid phosphatase (PAP), gamma-seminoprotein (gamma-Sm) and prostatic specific antigen (PSA) were measured in 31 hemodialysis patients without clinical signs of malignant disease. PAP, gamma-Sm and PSA levels in serum were not significantly different between control and hemodialysis groups. A significant reduction in these tumor markers was not found after dialysis treatment. This indicates that the measurement of PAP, gamma-Sm and PSA in serum is useful for the detection of prostatic cancer in patients undergoing hemodialysis.

Topics: Acid Phosphatase; Antigens, Neoplasm; Biomarkers, Tumor; Humans; Immunoenzyme Techniques; Kidney Failure, Chronic; Male; Middle Aged; Prostate-Specific Antigen; Prostatic Neoplasms; Prostatic Secretory Proteins; Proteins; Radioimmunoassay; Renal Dialysis; Seminal Plasma Proteins

Two cDNA clones containing the complete protein-coding sequence of 1,188 nucleotides as well as the 5' and 3' non-coding regions of human prostatic acid phosphatase (PAP) were isolated and sequenced. The size of PAP mRNAs from benign prostate hyperplasia and cancerous prostate was estimated to be 3.2Kb, indicating that the 3' downstream polyadenylation signal was used. Several genomic clones containing parts of the human PAP gene were isolated and the nucleotide sequence of ten exons and their flanking regions was determined. The protein-coding sequence of the human PAP gene was interrupted by nine introns. The positions of all nine introns present in the human PAP gene were homologous to those of the first nine introns in the human lysosomal acid phosphatase (LAP) gene. However, the last (11th) exon of the LAP gene encoding the COOH-terminal domain, which includes a transmembrane segment, was found to be absent in human PAP gene. Southern blot analysis of ten mammalian genomic DNAs gave multiple EcoRI fragments. The data of human genomic DNAs were consistent with the total length of the PAP gene of at least 50 kilobases.

Topics: Acid Phosphatase; Amino Acid Sequence; Base Sequence; Blotting, Northern; Blotting, Southern; Cloning, Molecular; DNA; DNA, Neoplasm; Exons; Genes; Genomic Library; Humans; Introns; Isoenzymes; Lysosomes; Male; Molecular Sequence Data; Poly A; Prostate; Prostatic Hyperplasia; Prostatic Neoplasms; Restriction Mapping; RNA; RNA, Messenger

A medium that had been conditioned by PC-3 cells stimulated the calcification of a human osteoblastic cell line, Tak-10, in a nonmitogenic culture. The calcification of the osteoblasts was stimulated maximally at a 25% concentration of the conditioned medium. Calcification activity was markedly enhanced by the addition of both prostatic acid phosphatase (PAP) and its substrate, alpha-glycerophosphate, to the medium; however, PAP added alone did not enhance this activity. These results suggest that human prostatic carcinoma cells produce a factor that stimulates the calcification of the human osteoblasts. Results have also suggested that PAP is a requisite for osteogenesis provided that its substrates are abundant in the medium.

Topics: Acid Phosphatase; Calcification, Physiologic; Cell Division; Culture Media; DNA; Glycerophosphates; Growth Substances; Humans; Male; Osteoblasts; Osteogenesis; Prostatic Neoplasms; RNA; Tumor Cells, Cultured

We determined the pre-analytical and biological variation of prostatic acid phosphatase and prostate-specific antigen in the same patient samples. Prostatic acid phosphatase and prostate-specific antigen were both stable when stored for at least 3 weeks with acidification (acetate buffer) or without acidification, except for prostate-specific antigen in samples stored unacidified at 4 degrees C. A significant elevation of prostate-specific antigen was noted in four patients with benign prostatic hyperplasia between 1/2 and 6 hours after prostatic massage. No significant effect was shown of changes in the glomerular filtration rate on prostate-specific antigen concentration, in spite of its low molecular mass. The estimate of within-subject biological variation showed a coefficient of variation of 33.8% for prostatic acid phosphatase and 14% for prostate-specific antigen. Desirable analytical imprecisions based on these findings were about 17% for prostatic acid phosphatase and 7% for prostate-specific antigen, these goals being achieved in practice for marker values higher than or equal to the upper reference limit.

Topics: Acid Phosphatase; Adenocarcinoma; Antigens, Neoplasm; Biomarkers, Tumor; Glomerular Filtration Rate; Humans; Male; Physical Examination; Prostate-Specific Antigen; Prostatic Diseases; Prostatic Hyperplasia; Prostatic Neoplasms

The biochemical markers alkaline phosphatase (Alk P), prostatic acid phosphatase (PAP) and prostate-specific antigen (PSA) were measured 3-monthly in 61 patients with disseminated prostatic cancer who were treated with LHRH analogues. The decrease in Alk P and PSA during the first 6 months of treatment was significantly related to a better survival. In this follow-up study, only PSA was useful for monitoring prostatic cancer during hormonal treatment. Before it was visible on a bone scan, PSA gave an indication of tumor progression. PSA might permit omission of routine bone scanning. Consensus must be obtained about the cost-saving use of biochemical markers in the treatment of disseminated prostatic cancer. With the number of treatment options increasing, objective measures are of utmost importance. Biochemical markers can be used for prognosis and monitoring of the treatment of patients with disseminated prostatic cancer.

Topics: Acid Phosphatase; Alkaline Phosphatase; Antigens, Neoplasm; Biomarkers, Tumor; Buserelin; Follow-Up Studies; Goserelin; Humans; Male; Prognosis; Prostate-Specific Antigen; Prostatic Neoplasms; Time Factors

A total of 133 patients underwent transperineal ultrasound-guided iodine 125 seed implantation for Stages A and B prostate cancer with a twenty-seven-month follow-up. There has been no mortality and our morbidity is no more than experienced after transurethral resection of the prostate. By using a Mick applicator our operating time is well under one hour, and our patients go home the same day without a Foley catheter. Our results indicate that patients with PSA values of less than 20 ng/mL (Yang method) and/or Gleason scores of 6 or less are excellent candidates for brachytherapy. By subdividing the percentage of normal PSA values in the follow-up periods according to the patient's original PSA value, further credence is given to the PSA value as a strong aid in staging when the Gleason score is 6 or less. Although the follow-up at twenty-seven months is small, our preliminary results indicate that brachytherapy is a viable option to radical surgery in those patients who are not good candidates for surgery or who prefer nonsurgical treatment.

Topics: Acid Phosphatase; Aged; Aged, 80 and over; Antigens, Neoplasm; Biomarkers, Tumor; Brachytherapy; Follow-Up Studies; Humans; Iodine Radioisotopes; Male; Middle Aged; Prostate-Specific Antigen; Prostatic Neoplasms; Time Factors; Ultrasonography; Urinary Retention

Sleep-related erections in 5 patients with stage T3N0M0 prostate cancer treated with a new nonsteroidal antiandrogen, Casodex, were evaluated with continuous monitoring of penile tumescence and rigidity on multiple nights. Mean serum luteinizing hormone levels were 7.2 +/- 1.2 IU/l. before therapy and increased to 14 +/- 3.6 IU/l. after 6 months of therapy. Serum testosterone and estradiol levels also increased from a basal level of 5.05 +/- 1.9 ng./ml. and 102 +/- 18 pmol./l., respectively, to 8.04 +/- 1.32 ng./ml. and 175 +/- 20 pmol./l., respectively, after 6 months of therapy. No significant modifications in regard to number of nocturnal penile tumescence episodes, maximum penile circumference and total rigidity time were found before and after therapy. Only 1 patient reported a decrease in sexual drive and libido. All patients presented with stable disease (National Prostatic Cancer Treatment Group criteria) and an unmodified performance status (Eastern Cooperative Oncology Group) after 6 months. Pure antiandrogen therapy did not seem to interfere significantly with the erectile capability of men with prostate cancer.

Topics: Acid Phosphatase; Androgen Antagonists; Anilides; Antigens, Neoplasm; Estradiol; Humans; Male; Middle Aged; Nitriles; Penile Erection; Prostate-Specific Antigen; Prostatic Neoplasms; Sleep; Testosterone; Tosyl Compounds

Human prostatic acid phosphatase (PAcP) is a tissue-specific differentiation antigen and is the major phosphotyrosyl (p-tyr) protein phosphatase in normal differentiated prostate epithelial cells. In prostate carcinomas, cellular PAcP has a low expression. We examined the expression of cellular PAcP activity and its correlation with cell growth that may lead us to understand the role of tyrosine phosphorylation in human prostate cells. LNCaP cells, which expressed the highest cellular PAcP activity, had the slowest growth rate and the lowest p-tyr level among three human prostate carcinoma cell lines: LNCaP, DU145, and PC-3. This inverse correlation was further examined in LNCaP cells, since these cells remain hormone-sensitive. Androgen, a classical stimulator of prostate cells, stimulated the growth of LNCaP cells while cellular PAcP activity decreased and p-tyr levels increased. This phenomenon was also observed when cells were treated with epidermal growth factor and fetal bovine serum. Both epidermal growth factor and fetal bovine serum stimulated the growth of LNCaP cells whereas cellular PAcP activity decreased. Furthermore, when cell growth was arrested at low temperatures (23 degrees C), cellular PAcP activity was elevated. To establish the relationship of cellular PAcP activity with cell growth rate, we transfected a complementary DNA encoding the full length PAcP protein into another human prostate carcinoma line, PC-3, that lacks endogenous PAcP. Two stable transfectants, designated PC-18 and PC-416 cells, were obtained and shown to express PAcP mRNA transcribed from the transfected complementary DNA. The expression of PAcP activity in PC-416 cells, but not PC-18 cells, was associated with a lower p-tyr level and a slower growth rate than control cells transfected with the expression vector alone. In conclusion, in LNCaP cells, the stimulated cell growth is associated with an increased p-tyr level and a decreased cellular PAcP activity. In PAcP complementary DNA-transfected PC-416 cells, the low level of p-tyr corresponds to a slow growth rate.

Topics: Acid Phosphatase; Base Sequence; Carcinoma; Cell Division; Dihydrotestosterone; DNA; Gene Expression; Humans; In Vitro Techniques; Male; Molecular Sequence Data; Oligodeoxyribonucleotides; Phosphotyrosine; Prostatic Neoplasms; RNA, Messenger; Transfection; Tumor Cells, Cultured; Tyrosine

The prognostic value was determined of prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP) measured before and after endocrine treatment in 57 patients with newly diagnosed Stage D2 prostatic cancer.. Therapy included orchiectomy or administration of luteinizing hormone releasing hormone analogues or an antiandrogen.. The absolute pretreatment PSA (elevated in 100% of patients) but not PAP (abnormal in 93%) predicted disease progression (P < 0.0011), i.e., a poor response to therapy. Fifty-three patients responded to androgen deprivation with a decrease in PSA level. This declined to normal at 3 and 6 months in 25% of patients. Forty-nine percent had a greater than 90% decrease in their PSA level. By 1 year, 58% of patients had progressive disease. Both the nadir PSA level and the percent decline from the pretreatment level at 3 and 6 months predicted the progression-free interval (P < 0.001). Patients with a 90% or greater decline in PSA had a prolonged progression-free survival. Serial PAP levels were similarly prognostic.. It was concluded that PSA was better than PAP in evaluating patients before and after androgen-deprivation therapy. The nadir level of both markers was an important tool to predict progression-free survival in patients with metastatic prostatic cancer.

Topics: Acid Phosphatase; Aged; Aged, 80 and over; Androgen Antagonists; Biomarkers, Tumor; Follow-Up Studies; Goserelin; Humans; Leuprolide; Male; Middle Aged; Neoplasm Staging; Orchiectomy; Prognosis; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Remission Induction; Time Factors

Topics: Acid Phosphatase; Androgen Antagonists; Biomarkers, Tumor; Humans; Male; Prognosis; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms

A modified method of retropubic radical prostatectomy was devised. The root of the penis was compressed and the bilateral internal iliac arteries were clamped before the dissection of the prostate. The urethra was divided at the junction of the prostate and bladder so that the bladder stump thus created has the size of the tip of the middle finger. Vesicourethral anastomosis was done by Vest procedure. By this method 24 patients were operated. All patients except one were alive without recurrence after the mean follow-up of 32 months. This method seems to be good enough to recommend.

Topics: Acid Phosphatase; Aged; Biomarkers, Tumor; Blood Loss, Surgical; Follow-Up Studies; Humans; Male; Middle Aged; Neoplasm Staging; Prognosis; Prostate-Specific Antigen; Prostatectomy; Prostatic Neoplasms

Natural killer (NK) cell activity was studied together with tumor marker serotests (PSA, PAP) and blood testosterone, estradiol, cortisol, and prolactin concentrations in treated prostate cancer patients. NK cell activity data were correlated with tumor stage (stage D0 + D1 versus stage D2) and showed statistically insignificant differences. Both tumor progression and stabilization of metastatic disease, triggered by the application of more appropriate therapy in progressive subjects, yielded low NK activity data. By contrast, normal NK activity was found during both partial remission of stage D2 tumor and stabilization of the same disease, after an initial period of tumor remission. Differences between NK activity data from the aforementioned two groups are statistically significant (P less than 0.01). In subjects examined, the application of NK activity assay to those with advanced disease reflected changes in the outcome of the treatment more closely than it did routine tumor marker assessment. The activity of NK cells seems unaffected by changes in basal blood estradiol, cortisol, testosterone, and prolactin concentrations that occur during therapy with pharmacological agents (estradiol, cyproterone acetate, diethylstilbestrol, and flutamide) and during surgical castration. The reported NK activity recordings in treated prostate cancer patients might be indicative of the presence of tumor cells in the circulation. If this holds true, the measurement of NK activity would appear to furnish urological oncology with a new tool for early, rapid recognition of progressive metastatic tumors.

Topics: Acid Phosphatase; Antineoplastic Agents; Biomarkers, Tumor; Cyproterone Acetate; Cytotoxicity Tests, Immunologic; Cytotoxicity, Immunologic; Diethylstilbestrol; Estradiol; Estramustine; Flutamide; Hormones; Humans; Hydrocortisone; Killer Cells, Natural; Male; Orchiectomy; Prolactin; Prostate-Specific Antigen; Prostatic Neoplasms; Radioimmunoassay; Testosterone

Previous studies from our laboratory have shown that reconstituted basement membrane and stromal secretory products are important regulators of benign prostatic epithelial cell growth and differentiation. In the present study we evaluated the impact of extracellular matrix (ECM) and soluble stromal secretory products on the proliferation and secretory activity of the androgen-responsive prostatic carcinoma cell line LNCaP. In these studies, dihydrotestosterone (DHT) was a potent mitogen for LNCaP cells cultured on plastic or on type I collagen. The growth response to DHT was greatly attenuated when LNCaP cells were grown on prostatic stromal ECM. Cells grown on stromal ECM also exhibited clustered morphology compared to the monolayer growth observed on plastic and secreted elevated levels of prostate specific antigen (PSA) and prostatic acid phosphatase (PAP). These findings indicate that cultivation of LNCaP on stromal ECM will promote the expression of differentiated functions. In additional studies, stromal cell conditioned medium (SCM) significantly increased PSA/PAP secretion by LNCaP cells in the presence of 10 nM DHT. The enhancement of DHT-induced PSA/PAP secretion by SCM was most pronounced when LNCaP cells were grown on stromal ECM. SCM did not significantly alter LNCaP proliferation. These studies indicate that prostatic stromal ECM and soluble secretory products will promote differentiated function in cultured LNCaP cells. In addition, we show that DHT can act as either a growth or differentiation-promoting stimulus depending on the presence of stromal factors.

Topics: Acid Phosphatase; Analysis of Variance; Basement Membrane; Biomarkers, Tumor; Blotting, Western; Cell Differentiation; Cell Division; Cell Line; Culture Media; Dihydrotestosterone; Dose-Response Relationship, Drug; Electrophoresis, Gel, Two-Dimensional; Extracellular Matrix; Gene Expression Regulation, Neoplastic; Humans; Male; Microscopy, Phase-Contrast; Prostate-Specific Antigen; Prostatic Neoplasms

Two hundred twenty asymptomatic males, aged 55 to 75 years old, underwent transrectal ultrasonography of the prostate as part of a screening examination. Fifteen prostate adenocarcinomas were detected, 5 of which were nonpalpable. The biopsies were performed under sagittal ultrasound guidance. Serum prostatic specific antigen and prostatic acid phosphatase levels were also obtained from each patient. Nine of the patients were staged as B2, one patient as D2, 4 patients as A1 and one as A2. The use of transrectal ultrasonography as a screening tool must be further evaluated in a multicenter trial with a large number of patients.

Topics: Acid Phosphatase; Adenocarcinoma; Aged; Biopsy; Humans; Male; Middle Aged; Neoplasm Staging; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Rectum; Ultrasonography

We discuss a 63-year-old man who presented with a metastatic tumor in an inguinal lymph node. By light microscopy, the tumor cells were characterized by a finely granular eosinophilic cytoplasm. A diagnosis of metastatic oncocytic carcinoma was made based on the results of an ultrastructural examination, which showed the cytoplasm of the tumor cells to be filled with mitochondria. Results of immunocytochemical studies showed positive reactivity for prostatic acid phosphatase and prostate-specific antigen. A transurethral resection of the prostate showed an oncocytic adenocarcinoma of the prostate, apparently the first of its kind, which was demonstrated to be the site of origin of the inguinal lymph node metastasis.

Topics: Acid Phosphatase; Adenocarcinoma; Adenoma; Cell Transformation, Neoplastic; Diagnosis, Differential; Eosinophilia; Humans; Hyperplasia; Immunohistochemistry; Lymphatic Metastasis; Male; Microscopy, Electron; Middle Aged; Mitochondria; Prostate-Specific Antigen; Prostatic Neoplasms

The ability of serum prostate specific antigen (PSA) and serum acid phosphatase (SAP) to identify skeletal spread was evaluated in untreated patients with prostatic cancer. Twenty patients with scintigraphic evidence of metastatic disease in bone (M1) at diagnosis were compared with 50 untreated patients in whom scans were repeatedly negative during long-term surveillance. Using the present laboratory upper limit of normal (ULN) of 3 iu/l, the sensitivity and specificity of SAP for M1 disease were 80 and 86% respectively. Stepwise discriminant analysis demonstrated that SAP was able to stage patients correctly (bone scan positive or negative) with 81% predictive accuracy at an optimum cut-off limit of 4.6 iu/l. By contrast, whilst PSA (Hybritech) was 100% sensitive for skeletal disease at 10 ng/ml--at the expense of poor (36%) specificity--analysis determined that an optimum cut-off limit of 58 ng/ml led to 79% predictive accuracy for disease in bone. It was concluded that PSA levels > 58 ng/ml are highly indicative of spread to the skeleton, even in the absence of radiological or scintigraphic evidence of metastases.

Topics: Acid Phosphatase; Biomarkers, Tumor; Bone and Bones; Bone Neoplasms; Humans; Male; Prostate-Specific Antigen; Prostatic Neoplasms; Radionuclide Imaging

Osteocalcin, a K-dependent vitamin protein, was studied in a group of advanced prostatic carcinoma patients to test the usefulness of this marker for diagnosing bone metastases. Osteocalcin levels were above the norm in 22 out of 27 patients with bone metastases, although high levels were not observed in patients without bone metastases. High sensitivity and specificity levels of serum osteocalcin appear to be strongly correlated to metastatic bone involvement and disease relapse after hormone treatment. Although these results must be confirmed on a larger series of patients, this protein appears to be a useful biological marker in prostatic cancer.

Topics: Acid Phosphatase; Aged; Biomarkers, Tumor; Bone Neoplasms; Follow-Up Studies; Gonadotropin-Releasing Hormone; Humans; Male; Osteocalcin; Prostate-Specific Antigen; Prostatic Neoplasms; Sensitivity and Specificity

We report our experience in the follow-up of 63 patients with advanced prostate adenocarcinoma. We used prostate-specific antigen and prostatic acid phosphatase in 27 patients; in 36 patients we evaluated osteocalcin and bone isoenzyme of alkaline phosphatase, two markers of bone metabolism which seem to be good markers in the follow-up of patients with bone metastases.

Topics: Acid Phosphatase; Adenocarcinoma; Alkaline Phosphatase; Biomarkers, Tumor; Bone and Bones; Follow-Up Studies; Humans; Isoenzymes; Male; Osteocalcin; Prostate-Specific Antigen; Prostatic Neoplasms

Serum levels of prostatic acid phosphatase (PAP) and prostate-specific antigen (PSA) were measured in 78 patients with benign prostate hyperplasia and compared with both the gland weight and the glandular component of prostatic tissue. Both PAP and PSA were significantly higher where prostate was heavier; however, we could not find a consistent factor which could correlate weight increase to marker levels. PSA tended to be higher when glandular component was more expressed. From the present findings we conclude that in patients with prostate cancer, PAP and PSA serum levels should be investigated considering also the benign components of prostate gland.

Topics: Acid Phosphatase; Biomarkers, Tumor; Humans; Male; Organ Size; Prostate-Specific Antigen; Prostatic Hyperplasia; Prostatic Neoplasms

We studied 78 men with suspicion of prostatic carcinoma, who underwent transrectal aspiration biopsy, diagnosing 46 adenocarcinoma, 13 chronic prostatitis and 19 benign prostatic hyperplasia. Moreover, we determined prostatic acid phosphatase (PAP) by enzyme immunoanalysis, resulting in 9/78 false-positives and 18/78 false-negatives. Also, we carried out a morphometric analysis of the cytologic samples which showed good correlation with the cytologic diagnosis except in the moderately differentiated carcinomas. We found a good correlation between PAP values, cytologic diagnosis and nuclear size as well as the percentage of the binucleolated cells.

Topics: Acid Phosphatase; Adenocarcinoma; Biopsy, Needle; Chronic Disease; False Negative Reactions; False Positive Reactions; Humans; Male; Prospective Studies; Prostatic Hyperplasia; Prostatic Neoplasms; Prostatitis

The authors measured serum prostate-specific antigen (PSA) and prostatic acid phosphatase concentration in histologically positive prostate hyperplastic and carcinomatous patients before, and 30-60 min and 24 h after prostate manipulation (rectal digital examination, cystoscopy and perineal punch biopsy). After rectal examination, PSA, and after other interventions, both markers changed significantly, although in different points of time and to a different extent. The authors call the attention to the importance of the point of time of the examination. Examination following prostate manipulation may result in wrong diagnosis or in erroneous therapeutic consequences in the follow-up period.

Topics: Acid Phosphatase; Biomarkers, Tumor; Biopsy; Cystoscopy; Follow-Up Studies; Humans; Male; Palpation; Physical Examination; Prostate; Prostate-Specific Antigen; Prostatic Hyperplasia; Prostatic Neoplasms; Time Factors

Serum values of prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP) were determined in 180 patients prior to pelvic lymphadenectomy and radical prostatectomy and in 40 patients prior to pelvic lymphadenectomy alone. In all tumor stages, PSA was superior to PAP in detecting cancer of the prostate. By PSA determination using a cutoff level of 4 ng/ml (Tandem assay), 28.8% of the patients with prostate cancer, stage pT2pN0M0, and 17.8% of the cases with a stage pT3pN0M0 tumor could not be detected. All these tumors had been noticed, however, by digital rectal examination. This indicates that PSA determination cannot replace digital rectal examination as a screening method for prostate cancer. In this study, it was possible neither by PSA nor by PAP to define a practicable cutoff level for patients with and without lymph node metastases. A clear differentiation between the stages pT2pN0M0 and pT3pN0M0 was not possible by either PSA or PAP alone.

Topics: Acid Phosphatase; Biomarkers, Tumor; Humans; Lymphatic Metastasis; Male; Neoplasm Staging; Prospective Studies; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms

Prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP) were determined in the serum of 69 patients with clinical T3/T4M0 prostatic cancer before staging lymphadenectomy. In principle, high-dose radiotherapy was given only to patients of pathological N0 category. Seventeen patients had a prelymphadenectomy PSA level below the normal upper reference limit (10 micrograms/l) and only 3 of them had pelvic lymph node metastases. Fifteen of 52 patients with a preoperative PSA level > or = 10 micrograms/l were of N0 category. Only 8 of the 41 evaluable patients had PAP values above the normal range, and 6 of these 8 patients had pelvic lymph node metastases. Preoperative PSA values, but not preoperative PAP levels, assist the clinician in predicting regional lymph node metastases in patients with clinical T3/T4M0 prostatic cancer. Two-thirds of the patients with T3/T4 tumours and PSA values between 10 and 50 micrograms/l have regional lymph node metastases. About 80% of the patients with PSA levels < 10 micrograms/l belong to the N0 category. About 75% of the patients with PSA > 50 micrograms/l have N+ disease. Taking into account the individual preoperative PSA values, the indication for preradiotherapy staging lymphadenectomy should be balanced between the chance of demonstrating N+ disease, the expected postoperative morbidity and the benefit for the patient found to be of N0 category.

Topics: Acid Phosphatase; Aged; Biomarkers, Tumor; Humans; Lymph Node Excision; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Staging; Pelvis; Predictive Value of Tests; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Sensitivity and Specificity

The authors report a patient who was admitted to the hospital with neurologic symptoms and signs that were thought to be caused by a primary intracranial tumor.. Craniotomy resulted in successful resection of an occipital lobe tumor reported histologically as a papillary adenocarcinoma, probably metastatic from the kidney. However, a complete diagnostic study failed to demonstrate the primary focus.. Thirteen months later, the patient was readmitted to the hospital and found to have metastatic prostatic carcinoma. Immunoperoxidase staining for prostatic acid phosphatase of the prostatic tissue and of the previously resected brain tumor tissue indicated that the brain lesion was metastatic from the prostate.

Topics: Acid Phosphatase; Adenocarcinoma, Papillary; Aged; Brain Neoplasms; Carcinoembryonic Antigen; Humans; Lumbar Vertebrae; Male; Prostatic Neoplasms; Spinal Neoplasms; Tomography, X-Ray Computed

Seventy-seven patients with prostatic cancer were treated at our department in the last 5 years. Of these patients 30 cases were followed by bone scintigraphy and serum PAP. In 27 follow-up scintigraphy procedures changes of bone scintigraphy corresponded to changes in serum PAP levels Changes of PAP levels did not always correspond to changes of scintigraphy, but almost all cases in which the level of PAP increased in a short period showed progression of bone metastasis. A 3-month interval between bone scintigraphy procedure in stage D2 prostatic cancer patients is generally recommended. However, we think that in prostatic cancer patients follow-up bone scintigraphy at regular short intervals is unnecessary if there is no change in serum PAP levels, symptoms or physical condition. Bone scintigraphy should be performed when the tumor marker changes rapidly or when any physical symptom appears.

Topics: Acid Phosphatase; Adenocarcinoma; Aged; Biomarkers, Tumor; Bone and Bones; Follow-Up Studies; Humans; Male; Prostatic Neoplasms; Radionuclide Imaging; Retrospective Studies

Prostate carcinoma is usually highly responsive to initial endocrine therapy. However, when relapse occurs, the subsequent clinical course is very poor. In this study, we tried to reveal the clinical aspects of bone-related relapse in 392 patients who received endocrine therapy for prostate carcinoma. In 17 stage B patients who had relapsed, 76% experienced relapse within 4 years following the start of treatment, 76% within 3 years in 27 stage C patients, and 71% within 2.5 years found in 45 stage D patients. Pre-treatment levels of serum enzymes and initial response of the primary lesion and of serum enzymes failed to predict relapse. The Gleason sum tended to be correlated with relapse. In particular, patients with a Gleason sum of 9-10 had a lower non-relapse rate during the follow-up period than patients with lower sums. With the recent use of more sophisticated measurements of PSA and/or PAP, the reduction rate or interval to normalization of the markers must be more relevant to predicting relapse.

Topics: Acid Phosphatase; Alkaline Phosphatase; Biomarkers, Tumor; Bone Neoplasms; Carcinoma; Combined Modality Therapy; Estrogens; Humans; L-Lactate Dehydrogenase; Male; Neoplasm Proteins; Neoplasm Staging; Orchiectomy; Prostatic Neoplasms; Treatment Outcome

A 66-year-old man presented with progressive proptosis of the left eye associated with ocular pain. A computed tomographic scan showed a high density mass in the posterolateral portion of the left orbit. The patient underwent surgical removal of the tumor and histopathological examination revealed adenocarcinoma of unknown origin. To find out the primary focus of the tumor the patient was referred to our department, where biopsy of the prostate revealed adenocarcinoma. Further, immunohistochemical examination of the orbital tumor was performed and prostatic acid phosphatase was identified. Finally, we made a diagnosis of orbital metastasis from prostatic carcinoma. This paper presents a rare case of prostatic carcinoma with orbital metastasis and reviews the literature of the subject.

Topics: Acid Phosphatase; Adenocarcinoma; Aged; Humans; Immunohistochemistry; Male; Orbital Neoplasms; Prostate; Prostatic Neoplasms

The aim of this study was to develop a method of quantitating prostate-specific acid phosphatase (PSAP) in histologic sections of prostate tumor tissue labeled with the peroxidase-antiperoxidase (PAP) complex technique using diaminobenzidine (DAB) as a substrate. Studies of PAP-DAB- and hematoxylin-stained prostate tissue sections were performed with a black-and-white, computerized microscope image system. The mass of brown reaction product generated in PAP-DAB staining was the indicator of PSAP intensity. The mass of brown reaction product was determined by using a dual wavelength method in which two 10-nm bandpass filters, peaked at 450 and 510 nm in wavelength, were used. The wavelength-dependent ratio of mass absorptivity of PAP-DAB stain (brown product) and that of hematoxylin (blue product) were estimated at wavelengths of 450 and 510 nm by using slides stained with only PAP-DAB or hematoxylin. The accuracy of the mass measurements, investigated by relating the measurement to the true mass of the brown PAP-DAB product, is reported. There was no significant difference between the measurements at magnifications of 10x, 20x, 40x or 60x in the reproducibility investigation. The PSAP stain intensity was quantitatively determined by the difference of the PAP-DAB stain mass per pixel between the tumor and normal cell region. The relationship between the objective measurement and the conventional subjective grades is presented.

Topics: 3,3'-Diaminobenzidine; Acid Phosphatase; Histocytochemistry; Humans; Image Processing, Computer-Assisted; Immunoenzyme Techniques; Male; Prostatic Neoplasms; Spectrophotometry

Topics: Acid Phosphatase; Anus Neoplasms; Carcinoma, Transitional Cell; Clinical Enzyme Tests; Diagnosis, Differential; Humans; Male; Prostate; Prostatic Neoplasms; Rectal Neoplasms

The antitumor activity of recombinant human tumor necrosis factor (rhTNF) against heterotransplanted human prostatic carcinoma (PC-3) and spontaneous lymphatic tumor metastasis was studied in vivo. The spontaneous lymphatic metastasis of PC-3 tumor was found in approximately 50% of cases. Significant antitumor activity was observed with repeated intratumoral administration of a large dose of rhTNF, not only on the subcutaneous tumor xenografts but also on the lymph node metastases. Strong antitumor activity could be achieved even with the intratumoral administration of a small dose of rhTNF in combination with mild hyperthermia on either the transplanted tumors or on the metastatic tumors.

Topics: Acid Phosphatase; Animals; Combined Modality Therapy; Humans; Hyperthermia, Induced; Lymphatic Metastasis; Male; Mice; Mice, Nude; Neoplasm Transplantation; Prostate; Prostatic Neoplasms; Recombinant Proteins; Transplantation, Heterologous; Tumor Necrosis Factor-alpha

This study of 133 patients with localized prostate cancer (Stages A2 to C), treated by external beam radiation therapy (XRT), was undertaken for two reasons: (1) to investigate the usefulness of pretreatment serum prostate-specific antigen (PSA) levels in evaluating patients before XRT; and (2) to investigate post-XRT changes in PSA values and their likely clinical significance. It was found that pretreatment PSA values in patients with localized disease exhibit wide patient to patient variability with a greater than 100-fold difference between the lowest and highest values. Although mean PSA values were significantly higher in Stage C disease (51 patients; mean PSA, 17.3 ng/ml) than in Stage A2 disease (31 patients; mean PSA, 9.0 ng/ml), Stage B1 disease (23 patients; mean PSA, 9.1 ng/ml), or Stage B2 disease (28 patients; mean PSA, 10.6 ng/ml), individual values were of virtually no help in assigning individual patients to a clinical stage. PSA levels did not correlate with grade. After XRT, PSA values fell significantly and dramatically in virtually all patients (98%) by 3 months follow-up. Mean PSA fell from 12.5 to 2.6 ng/ml, and median PSA fell from 6.6 to 1.9 ng/ml. In most patients, PSA continued to fall up to 12 months after XRT and then stabilized at 21 months. Although PSA values fell dramatically after XRT, PSA was detectable in the serum of all patients. PSA values tended to transiently and mildly elevate during XRT. In a small proportion of patients, rising PSA values were observed after 6 months. The full significance of this requires further follow-up, of four such patients, one has relapsed. PSA is a more sensitive marker of prostatic radiation than prostatic acid phosphatase.

Topics: Acid Phosphatase; Adenocarcinoma; Aged; Antigens, Neoplasm; Biomarkers, Tumor; Combined Modality Therapy; Follow-Up Studies; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Prostate-Specific Antigen; Prostatic Neoplasms

Since the introduction of hormonal therapy for the treatment of metastatic prostatic adenocarcinoma, there have been 33 reports of metastases of prostate carcinoma to the breast. We report two cases of diethylstilbestrol (DES)-treated patients with metastatic prostate adenocarcinoma who developed breast masses. The lesions had infiltrative patterns simulating primary breast carcinoma. Immunoperoxidase stains, prostate-specific antigen (PSA), and prostatic acid phosphatase (PAP) were positive, identifying these cases as metastatic prostatic carcinoma to the breast. Differentiating primary from secondary tumors in these patients is difficult since there have been 10 reports of primary breast carcinoma occurring in DES-treated patients with prostatic adenocarcinoma. Their differentiation is important to direct appropriate therapy, and PSA and PAP immunoperoxidase stains are important in their correct classification.

Topics: Acid Phosphatase; Adenocarcinoma; Antigens, Neoplasm; Breast Neoplasms; Diethylstilbestrol; Female; Humans; Immunohistochemistry; Male; Middle Aged; Prognosis; Prostate-Specific Antigen; Prostatic Neoplasms

Twenty-seven cases of reactivated prostatic cancer between 1979 and 1990 were investigated. Reactivation took place in the form of local aggravation in 3 cases, occurrence or aggravation of metastasis to bones in 8 cases, and in both forms in 16 cases. The elevation of tumor markers preceded the clinical findings in 11 cases (41%). In 75% of the cases with occurrence or aggravation of metastasis, the elevation of tumor markers preceded the clinical findings. This showed that tumor markers were useful in most cases for early detection of reactivation. However, in 3 cases with local aggravation, the clinical findings preceded the elevation of tumor marks. Therefore, it is also important to check the clinical findings at the follow-up. At the time of reactivation, positive rates of prostatic acid phosphatase (PAP), gamma-seminoprotein (gamma-Sm) and prostatic specific antigen (PA) were 78%, 83% and 80%, respectively. Thus gamma-Sm and PA appeared to be more reliable than PAP for monitoring of prostatic cancer.

Topics: Acid Phosphatase; Antigens, Neoplasm; Biomarkers, Tumor; Humans; Male; Prostate-Specific Antigen; Prostatic Neoplasms; Prostatic Secretory Proteins; Proteins; Seminal Plasma Proteins

Prostate specific antigen (PSA) levels were determined in 78 patients judged clinically to be free of disease at intervals of 36 or more months (range 38 to 186 months, median 87 months) after completion of irradiation therapy by 125iodine implantation or external beam radiation. Of this select group of patients 38% had undetectable serum PSA levels (0.5 ng./ml. or less) and 38% had PSA levels that were within normal limits (4.0 ng./ml. or less). All stages and grades were represented. Undetectable PSA levels were only rarely found (3%) in patients with carcinoma of the prostate before treatment. In 24 of these 78 patients a negative biopsy of the irradiated prostate had been obtained 18 to 42 months after treatment. When the PSA level was drawn, which ranged from 7 to 16 years after treatment, an equal percentage of these biopsied patients had either an undetectable, normal or elevated level. Irradiation is able to decrease PSA to undetectable levels in some patients with prostatic carcinoma. Whether this reflects suppression of marker production alone or, more importantly, ablation of prostate cancer producing that marker remains to be determined.

Topics: Acid Phosphatase; Antigens, Neoplasm; Biomarkers, Tumor; Brachytherapy; Follow-Up Studies; Humans; Iodine Radioisotopes; Male; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Radioimmunoassay; Radiotherapy, High-Energy; Time Factors

Prostate-specific antigen (PSA) has been shown to be a more sensitive tumor marker than prostatic acid phosphatase (PAP) in prostatic adenocarcinoma: PSA was positive in 54 of our 117 patients (46%) and PAP was positive in 24 (21%). In order to compare the usefulness of these markers during and after radiotherapy serum samples from 24 patients treated with external beam irradiation were analyzed. PAP was only slightly positive in 1 patient (4%) after radiotherapy. His PSA level was highly elevated and he died of progressive disease. In the other 23 patients the cancer was in local control. However, the serum PSA level remained positive in 5 of these patients indicating vital cancer cells may still have been present. An alternative possibility is that metaplastic prostatic cells which secrete PSA were left after radiotherapy, as has been shown to be the case in prostatic hyperplasia. Before radiotherapy increased PSA levels were measured in 3 patients. In 2 of them the level declined to normal within 6 months after radiotherapy. The PAP levels were normal. It is concluded that PSA (positive in 25% of patients after radiotherapy) might be more sensitive than PAP (positive in 4%) in monitoring the effect of radiotherapy in prostatic cancer patients.

Topics: Acid Phosphatase; Adenocarcinoma; Aged; Antigens, Neoplasm; Biomarkers, Tumor; Follow-Up Studies; Humans; Male; Middle Aged; Prostate-Specific Antigen; Prostatic Neoplasms

The comparison of the diagnostic and prognostic significance of histology, immunohistochemical parameters (PSA, PSP), and silver-stained nucleolar organizer regions (AgNORs) was estimated in paraffin sections taken of 63 prostatic carcinomas prior to therapy. AgNORs were visualized with a one-step silver staining technique with the appropiate staining time determined by preliminary staining-time series. The mean AgNOR number per cell (n) and the mean AgNOR area per silver-stained dot (A) were determined by means of an automatic image analysis system. Thereby prostatic carcinomas exhibited multiple small AgNORs within their nuclei (n = 4.7, A = 0.09 micron 2), whereas benign prostatic epithelium showed few but large silver-stained particles (n = 1.8, A = 0.27 micron 2; p less than 0.001). This relationship was then calculated as a quotient of AgNOR number and area (NQ = n/A) which provided additional information for the diagnosis of malignancy as well as survival. Univariate survival analysis disclosed a set of four variables predicting death from prostatic cancer; cribriform growth pattern, AgNOR quotient, histological grade, and PSA immunoreactivity. Of these parameters, immunoreactivity of PSA failed to prove its prognostic significance in multivariate survival analysis (Cox model). No relation to prognosis was found for the number as well as the area of AgNORs alone. Therefore, image analysis proved to be a prerequisit for the feasibility of this promising technique by providing objective and reproducible results.

Topics: Acid Phosphatase; Aged; Aged, 80 and over; Antigens, Neoplasm; Biomarkers, Tumor; Humans; Image Processing, Computer-Assisted; Male; Middle Aged; Neoplasm Staging; Nucleolus Organizer Region; Prognosis; Prostate-Specific Antigen; Prostatic Neoplasms; Staining and Labeling; Survival Analysis

Of 91 patients with prostatic cancer treated at our Department of Urology, from January 1976 through December 1987, 42 cases of stage D2 cancer treated with endocrine therapy were evaluated retrospectively with regard to clinical parameters and prognoses. The patients with marked increase in the level of the prostatic acid phosphatase (PACP), and the lactate dehydrogenase (LDH) in serum, and marked decrease in volume of hemoglobin (Hb) had a poor prognosis. The patients who took a long time to obtain a favorable response to the therapy had a poor prognosis. The response grade in NPCP criteria at 3 months after the initiation of therapy reflected the prognosis, and showed good correlation to the grade of favorable response.

Topics: Acid Phosphatase; Adenocarcinoma; Aged; Aged, 80 and over; Chlormadinone Acetate; Combined Modality Therapy; Diethylstilbestrol; Hemoglobins; Humans; L-Lactate Dehydrogenase; Male; Middle Aged; Neoplasm Staging; Orchiectomy; Prognosis; Prostatic Neoplasms; Retrospective Studies; Survival Rate

Preoperative intra-individual variation for determinations of prostate-specific antigen and prostatic acid phosphatase concentrations, 15-30% in 92 patients with benign prostatic hyperplasia, limits the diagnostic usefulness of both tumor markers. In benign prostatic hyperplasia (214 patients), concentrations of these tumor markers increased in the initial postoperative period. Prostatic acid phosphatase concentration then decreased by the third postoperative day. Prostate-specific antigen concentration remained above normal in the first postoperative week but had decreased by 42 days. In prostatic carcinoma (46 patients), the concentrations of these tumor markers did not increase postoperatively. During the first week, the concentrations of prostatic acid phosphatase began to fall, but prostate-specific antigen showed a decrease only at 42 days. After orchidectomy (11 patients), the concentrations of both markers had decreased by five days. Concentrations of prostate-specific antigen but not of prostatic acid phosphatase were significantly increased in patients with metastases at 42 days postoperatively. When the concentration of tumor marker did decrease, the magnitude of change was greater for prostatic acid phosphatase than for prostate-specific antigen. These changes were accentuated after an orchidectomy.

Topics: Acid Phosphatase; Antigens, Neoplasm; Carcinoma; Humans; Immunoradiometric Assay; Male; Orchiectomy; Postoperative Period; Prospective Studies; Prostate; Prostate-Specific Antigen; Prostatectomy; Prostatic Hyperplasia; Prostatic Neoplasms; Reference Values

Serum levels of prostatic acid phosphatase (PAP), gamma-seminoprotein (gamma-Sm) and prostate-specific antigen (PSA) were determined simultaneously in 57 patients with benign prostatic hyperplasia (BPH) and in 50 untreated patients with prostatic cancer (adenocarcinoma, N = 47 and non-adenocarcinoma, N = 3). The correlations between the serum levels of gamma-Sm and PSA in these patients were assessed by linear regression analysis. Some fundamental studies were added for explaining the causes of discrepancy between the serum levels of gamma-Sm and PSA. All of BPH group underwent transurethral resection of the prostate (TURP) and the sera were obtained for measurements before, immediately after and 18 hours after TURP. The gamma-Sm correlated well with the PSA in the sera obtained before (r = 0.76) and 18 hours after (r = 0.73) TURP. However, there was no correlation (r = 0.26) between them in the sera obtained immediately after TURP. In 47 untreated patients with adenocarcinoma of the prostate, no significant correlation (r = 0.19) between serum levels of gamma-Sm and PSA was observed, although there was correlation (r = 0.51) between those of PAP and PSA. When these patients were classified into two groups, M0 (stage A-C; N = 26) and M1 (stage D; N = 21), however, the serum gamma-Sm correlated with the serum PSA in M0 group (r = 0.57), but didn't in M1 group (r = 0.11). Furthermore, the differences in the means of PAP (p less than 0.05) and PSA (p less than 0.001) between M0 group and M1 group were statistically significant, although the serum gamma-Sm failed to distinguish M0 from M1. The anti-PSA antibody of "PSA Kit" reacted against the standard gamma-Sm adopted from "gamma-Sm Kit". Surprisingly, the anti-gamma-Sm antibody of "gamma-Sm Kit" also reacted against the standard PSA adopted from "PSA Kit". The gamma-Sm and PSA apparently cross-reacted each other. The quantitative analyses with serial dilution of the sera were done by using each assay in 3 patients whose serum levels of gamma-Sm were markedly different from those of PSA. The dilution curve for PAP appeared to be rectilineal, and that for PSA also appeared to be approximately rectilineal. However, the gamma-Sm assay failed to be proportional. In conclusion, the correlation between serum levels of gamma-Sm and PSA was absent in certain circumstances, when the true values of them were expected to be much higher than those determined.(ABSTRACT TRUNCATED AT 400 WORDS)

Topics: Acid Phosphatase; Adenocarcinoma; Antigens, Neoplasm; Biomarkers, Tumor; Humans; Male; Prostate-Specific Antigen; Prostatic Hyperplasia; Prostatic Neoplasms; Prostatic Secretory Proteins; Proteins; Seminal Plasma Proteins

A total of 132 patients with stage A1 adenocarcinoma of the prostate was followed for 5 to 23 years (mean 8.2 years). Of these patients 52 underwent a second staging transurethral resection of the prostate between 1977 and 1986. Progressive disease developed in 3 of the 12 patients (25%) in whom residual foci of well differentiated cancer were detected by the second transurethral resection and who did not undergo further treatment. Of the 38 patients in whom the second transurethral resection did not detect residual cancer 3 (8%) also had progressive disease. From April 1989 to December 1989, 44 patients were re-evaluated by transrectal ultrasonography and ultrasonographically guided biopsies. Of these patients 3 had locally progressive disease. Progressive disease also developed in 4 more patients. Thus, 13 of the 132 patients (10%) had either locally or systemically progressive disease after long-term followup. The interval from diagnosis of stage A1 disease to detection of progression ranged from 6 months to 20 years (mean 7 years). Ten patients underwent definitive treatment for what was believed to be locally progressive disease, 2 underwent palliative therapy and 1 had no therapy due to poor physical condition. Of the 10 patients who underwent definitive therapy 6 are alive without evidence of disease, 2 died of unrelated causes without evidence of disease and 2 are alive with stage D1 disease. These data suggest that patients in whom a second staging transurethral resection of the prostate detects residual cancer have a high probability of progressive disease. Also, negative findings from a second staging transurethral resection may not exclude the possibility of disease progression. Expectant management of stage A1 disease is warranted but regular and long-term followup is mandatory.

Topics: Acid Phosphatase; Adenocarcinoma; Aged; Aged, 80 and over; Antigens, Neoplasm; Biomarkers, Tumor; Biopsy, Needle; Combined Modality Therapy; Follow-Up Studies; Humans; Male; Middle Aged; Neoplasm Staging; Prostate; Prostate-Specific Antigen; Prostatectomy; Prostatic Neoplasms; Reoperation; Retrospective Studies; Ultrasonography

A prostatic lesion, histologically identical to sclerosing adenosis of the breast, was found in five (1.9%) of 263 patients who underwent transurethral resection, open prostatic adenectomy, radical prostatectomy, or total cystoprostatectomy. This uncommon lesion was a localized proliferation of crowded small glands, small solid nests, and individual cells embedded in a cellular stroma, mimicking a small acinar prostatic adenocarcinoma. The proliferating glands were lined by a single layer of secretory cells surrounded by an eosinophilic membranous structure. Basal cells were disclosed in individual glands or as small nests and even individual cells with immunostainability for basal cell-specific cytokeratin (EAB903), S-100 protein, and muscle-specific actin (HHF35). These findings indicate the benign nature of the lesion with myoepithelial differentiation of the basal cells. In contrast, all 25 small acinar adenocarcinomas examined as controls lacked positive stains for the above three antibodies, verifying the usefulness of these antibodies to distinguish between this benign lesion from adenocarcinoma.

Topics: Acid Phosphatase; Actins; Adenocarcinoma; Aged; Aged, 80 and over; Antigens, Neoplasm; Diagnosis, Differential; Humans; Immunohistochemistry; Keratins; Male; Prostate-Specific Antigen; Prostatic Diseases; Prostatic Neoplasms; S100 Proteins; Sclerosis

We conducted mass screenings for prostate diseases on male subjects over fifty years of age in three separate areas in Hokkaido. Prostate carcinoma and benign prostatic hypertrophy were searched in the 1,764 participants. Histopathologically proven prostate carcinoma was found in twenty-two (1.25%) of the 1,764 participants. This frequency of carcinoma was higher than any other carcinoma found in the mass screenings for gastric, uterine, breast and lung carcinoma in Hokkaido. Of the 22 prostate carcinomas found, 68% were in the early stage (stage B). This stage distribution was clearly distinct from that of prostate carcinoma found on the hospital visit, most of which had already progressed to an advanced stage. These results indicate that mass screening for prostate carcinoma on greater than or equal to 50 year old-male subjects is efficient in finding carcinoma of all stages but, in particular, carcinoma of early stage, when compared with mass screening for other carcinomas. BPH, defined as a moderately or markedly enlarged prostate on rectal palpation, was found in 10% of the participants. Questionnaire on subjective symptoms of voiding disturbance in the participants has confirmed that these symptoms, mainly elicited by BPH, become manifested in fifties and more frequent with age. Of thirteen patients with prostate carcinoma who received both rectal examination and prostate-related markers measurement in serum at the time of mass screening, three without induration of the prostate were diagnosed as having carcinoma from an abnormal value of the serum markers. This result suggests that the marker(s) is one of the useful screening tests for detecting carcinoma.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acid Phosphatase; Aged; Aged, 80 and over; Antigens, Neoplasm; Biomarkers, Tumor; Humans; Japan; Male; Mass Screening; Middle Aged; Prostate-Specific Antigen; Prostatic Hyperplasia; Prostatic Neoplasms; Prostatic Secretory Proteins; Proteins; Seminal Plasma Proteins; Surveys and Questionnaires

The clinical significance of serum basic fetoprotein (BFP) in prostatic cancer was investigated together with serum prostatic acid phosphatase (PAP), gamma-seminoprotein (gamma-Sm) and prostate specific antigen (PA). Investigated in this study were 40 patients with prostatic cancer, ranging in age from 50 to 85 years (mean age: 69.5 years). According to clinical staging, 3 cases (7.5%) had a stage A disease, 10 cases (25.0%) a stage B disease, 7 cases (17.5%) a stage C disease, and 20 cases (50.0%) a stage D disease. The positive rates for serum BFP, PAP, gamma-Sm, and PSA were 60.0, 45.0, 63.6, and 68.4%, respectively, and these rates increased as the stage advanced. The above results suggest that BFP is the most useful marker of the four for monitoring prostatic cancer. In a combination assay of these four markers, 29 (87.9%) of 33 patients with prostatic cancer could be diagnosed by observing an elevated serum level in one of the markers. This suggests that a combination assay of BFP, PAP, gamma-Sm and PSA in patients with prostatic cancer is useful for diagnosis and monitoring of the disease.

Topics: Acid Phosphatase; Aged; Aged, 80 and over; alpha-Fetoproteins; Antigens, Neoplasm; Biomarkers, Tumor; Humans; Immunoenzyme Techniques; Male; Middle Aged; Prostate-Specific Antigen; Prostatic Neoplasms; Prostatic Secretory Proteins; Proteins; Radioimmunoassay; Seminal Plasma Proteins

We have previously reported the identification and basic characterization of two biallelic TaqI RFLPs, A and B, of the 3' end of the human ACPP locus in an unselected Finnish population (Winqvist et al., 1989). In the present investigation, a similar allelic distribution was observed in patients with prostatic cancer or benign hyperplasia. In addition, it was found that the DNA sequences generating RFLP-B are located further downstream from the RFLP-A sequences.

Topics: Acid Phosphatase; Deoxyribonucleases, Type II Site-Specific; DNA; DNA Probes; Genotype; Humans; Male; Polymerase Chain Reaction; Polymorphism, Restriction Fragment Length; Prostate; Prostatic Hyperplasia; Prostatic Neoplasms

A quadruple tumor marker serotest assay (neurone-specific enolase, NSE, prostate-specific antigen, PSA, prostatic acid phosphatase, PAP, and carcino-embryonic antigen, CEA) was performed on sera from both 63 patients with untreated prostate cancer and 135 patients treated with orchiectomy, flutamide, diethylstilbestrol (DES), cyproterone acetate (CPA), and Estracyt. In untreated patients with local tumor elevated blood NSE concentrations were found more frequently (10/35, 28.6%) than in untreated subjects with disseminated disease (3/28, 10.7%). Elevated NSE values were measured more frequently in nonresponders to therapy 10/46 (21.7%), than in responders during prostate cancer partial remission (2/89, 2.2%). In none of NSE-positive neoplasms a small cell prostate cancer has been histologically detected. Many of NSE-positive tumors are also closely associated with elevated blood CEA values. The applied anticancer drugs were inefficient in the normalization of neither one from the pair of elevated NSE and CEA concentrations (regardless of the numerical values of the other two markers, PSA and PAP), but their values were found to decline occasionally only after surgical treatment. In patients with raised PSA, PAP, and CEA levels but with a normal NSE value, the application of the same treatment strategies was in the most of subjects sufficient to provoke either temporary or even lasting tumor response to therapy. Hence, it appears that the assessment of the NSE serotest, despite its minimal value in the overall tumor staging and monitoring, might furnish the decision-making step related to the treatment of aggressive prostate cancer with an additional and powerful tool.

Topics: Acid Phosphatase; Antigens, Neoplasm; Antineoplastic Agents; APUD Cells; Biomarkers, Tumor; Carcinoembryonic Antigen; Cyproterone; Cyproterone Acetate; Diethylstilbestrol; Estramustine; Flutamide; Humans; Male; Orchiectomy; Phosphopyruvate Hydratase; Prostate-Specific Antigen; Prostatic Neoplasms

Clinical understaging abounds in adenocarcinoma of the prostate. The preoperative prostate-specific antigen is not useful in preoperative staging, although enzymatic acid phosphatase elevation is associated with positive nodes in two-thirds of patients. Whole mount evaluation of radical prostatectomy specimens reveals tumor multicentricity in more than half the patients and tumor extension beyond the prostatic capsule in the majority of patients. A significant number of patients have a final tumor grade higher than that initially assigned. Capsule penetration by tumor is a factor of tumor grade as is volume.

Topics: Acid Phosphatase; Adenocarcinoma; Antigens, Neoplasm; Biomarkers, Tumor; Biopsy; Humans; Lymph Node Excision; Lymph Nodes; Male; Predictive Value of Tests; Prostate-Specific Antigen; Prostatic Neoplasms

Serum gamma-seminoprotein (gamma-Sm) was evaluated as a new marker for prostatic cancer in comparison with prostatic acid phosphatase (PAP). The sensitivity of gamma-Sm and PAP for untreated prostatic cancer was 81% and 67%, respectively. gamma-Sm showed a higher positive rate over all stages than in benign prostatic hypertrophy (BPH). There was no correlation between gamma-Sm and PAP in prostatic cancer. Improved sensitivity was obtained by simultaneous measurement of gamma-Sm and PAP. Specificity of gamma-Sm and PAP for BPH was 87% and 90%, respectively. gamma-Sm normalized after endocrine therapy for stage D2 more often than did PAP. These results indicate that gamma-Sm is another useful marker to evaluate prostatic cancer.

Topics: Acid Phosphatase; Antigens, Neoplasm; Biomarkers, Tumor; Humans; Male; Prostatic Hyperplasia; Prostatic Neoplasms; Prostatic Secretory Proteins; Proteins; Seminal Plasma Proteins; Sensitivity and Specificity

To determine the value of prostatic markers for prostate cancer, serum prostatic acid phosphatase (PAP), prostate specific antigen (PSA) and gamma-Seminoprotein (gamma-Sm) were measured in 81 patients with benign prostatic hypertrophy and in 12 patients with incidental prostatic cancer. gamma-Sm was the most sensitive but the least specific of the three markers. Large prostate glands, especially hyper-glandular type tended to be associated with high gamma-Sm levels in our study. Patients with acute urinary retention, acute prostatitis and necrosis also showed positive markers. Out of 12 patients with incidental cancer, 5 patients had more than 2 elevated markers. Four patients with poorly differentiated adenocarcinoma failed to show increased markers.

Topics: Acid Phosphatase; Adenocarcinoma; Aged; Antigens, Neoplasm; Biomarkers, Tumor; Humans; Male; Middle Aged; Neoplasm Staging; Prostate-Specific Antigen; Prostatic Hyperplasia; Prostatic Neoplasms; Prostatic Secretory Proteins; Proteins; Seminal Plasma Proteins

Serial serum prostatic acid phosphatase (PAP) and prostate specific antigen (PSA) measurements were performed in 871 patients treated with hormonal combination therapy for stage C (95 patients) or stage D2 (776) prostate cancer for an average followup of 26 months. The relative efficacy of serum PAP and PSA for predicting recurrence of the disease was evaluated by 2 statistical methods at the time of progression as well as 6 and 12 months before clinical relapse of disease using optimized cut-off values of 2.0 and 4.0 micrograms/l. for serum PAP and PSA, respectively. At the time of progression the sensitivity (plus or minus standard deviation) of the 2 tests was estimated at 61.1 +/- 3.2% and 86.7 +/- 3.1% for PAP and PSA, respectively, while the specificity (plus or minus standard deviation) was calculated at respective values of 79.6 +/- 1.3% and 92.4 +/- 4.1%. Receiver operating characteristic analysis disclosed a greater accuracy for PSA at 89.2 +/- 1.7% versus 78.7 +/- 1.6% (plus or minus standard deviation) for PAP. The somewhat lower positive predictive value of the PSA test (81.4% versus 89.6%) is more than compensated by its superior negative predictive value (92.4% versus 79.6%). The present data also show that serum PSA measurements are superior to those of serum PAP for predicting disease recurrence in stages C and D prostate cancer patients treated by combination endocrine therapy and they indicate that measurement of serum PAP does not add significantly to single measurement of serum PSA alone.

Topics: Acid Phosphatase; Aged; Antigens, Neoplasm; Biomarkers, Tumor; Humans; Male; Middle Aged; Predictive Value of Tests; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; ROC Curve; Sensitivity and Specificity

The aim of this study was to assess the diagnostic value of five biological markers--prostate acid phosphatase (PAP), prostate specific antigen (PSA), tartrate resistant (Tr-ACP), and tartrate labile (TI-ACP) acid phosphatases, and alkaline phosphatase bone isoenzyme (B-ALP)--for the detection of bone metastases in patients with prostate carcinoma. Using the Tc-99m HMDP bone scans of 80 patients scored from 0 (normal) to 2 (diffuse bone involvement) as the "gold standard," a receiver operating characteristic (ROC) analysis was performed. This method allows the determination of different threshold values (corresponding to different couples of sensitivity and specificity) for the assays. An ROC curve comparison was also performed. Results show that B-ALP is the best test for such detection (area under the ROC curve = 0.93; Spearman Rank correlation with bone scan r' = 0.81). Among the other markers, PSA was found to be the best (area under the ROC curve = 0.81; Spearman Rank correlation with bone scan r' = 0.58). In addition to the prostatic tumor markers (PSA and PAP), we suggest the use of the low-cost B-ALP assay in the follow-up of prostate carcinoma patients to determine the optimum moment to perform a bone scan. A normal result of this assay indicates a very low probability of bone metastasis; conversely, raising of B-ALP concentration must lead to a bone scan.

Topics: Acid Phosphatase; Aged; Alkaline Phosphatase; Antigens, Neoplasm; Biomarkers, Tumor; Bone and Bones; Bone Neoplasms; Evaluation Studies as Topic; Humans; Isoenzymes; Male; Prostate-Specific Antigen; Prostatic Neoplasms; Radionuclide Imaging; ROC Curve; Sensitivity and Specificity; Technetium Tc 99m Medronate

Serum prostatic acid phosphatase (PAP), gamma-seminoprotein (gamma-Sm), and prostate-specific antigen (PA) levels were measured in 63 untreated patients with prostatic cancer. The sensitivities of PAP, gamma-Sm, and PA as markers of malignancy were 68%, 83%, and 77%, respectively. The latter two markers were more sensitive than PAP, especially in stage B disease. The specificities of PAP, gamma-Sm, and PA were 95%, 93%, and 93%, respectively. Patients with multiple positive markers were very likely to have prostatic cancer. In reactivation of the disease, positive rates for gamma-Sm and PA were higher than for PAP, indicating that the former two markers are more reliable for monitoring prostatic cancer.

Topics: Acid Phosphatase; Antigens, Neoplasm; Biomarkers, Tumor; Humans; Male; Prostate; Prostate-Specific Antigen; Prostatic Hyperplasia; Prostatic Neoplasms; Prostatic Secretory Proteins; Proteins; Seminal Plasma Proteins

A total of 71 prostatic tumour patients and 45 prostatic adenoma patients were tested for prostate-specific antigen (PSA), immunological prostatic acid phosphatase (PAP) concentration as well as serum prostatic phosphatase (SPP) and enzymic serum phosphatase. It was found among untreated patients that PSA showed the highest percentage of pathologic affection in each stage. PSA, on the evidence of clearance test in the initial days of therapy and after a follow-up period of several months, gave a good picture of the course that the disease had taken.

Topics: Acid Phosphatase; Aged; Aged, 80 and over; Antigens, Neoplasm; Biomarkers, Tumor; Humans; Male; Middle Aged; Phosphoric Monoester Hydrolases; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms

Enzymatic assays for tartrate-sensitive acid phosphatase and beta-glucuronidase, and radio-immunoassay for prostate-specific antigen, were modified for application to fine-needle aspirate samples from benign and malignant human prostates. When compared to samples from benign prostates, the ratio of acid phosphatase to beta-glucuronidase activities was significantly decreased in needle aspirates from malignant prostates. Prostate-specific antigen values in the aspirates did not correlate with malignancy.

Topics: Acid Phosphatase; Antigens, Neoplasm; Biomarkers, Tumor; Biopsy, Needle; Clinical Enzyme Tests; Glucuronidase; Humans; Male; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms

Serum prostatic acid phosphatase activity and prostate specific antigen levels were measured in the serum of 113 patients undergoing transurethral resection of an enlarged prostate gland, and the results compared with the histological diagnosis. Prostate-specific antigen was found to be the more sensitive indicator of malignancy, but prostatic acid phosphatase was more specific.

Topics: Acid Phosphatase; Antigens, Neoplasm; Biomarkers, Tumor; Humans; Male; Prostate-Specific Antigen; Prostatic Neoplasms

In order to identify the endogenous phosphoprotein substrates for human prostatic acid phosphatase (PAP), cellular proteins of human normal, benign, and malignant prostatic tissues as well as carcinoma cell lines were phosphorylated by the cellular kinases in the presence of (gamma-32P)-ATP and then were subjected to dephosphorylation reaction by PAP. Of several endogenous phosphoproteins, PAP preferentially dephosphorylated a cytosolic protein of Mr 83 kDa. The dephosphorylation of the 83 kDa phosphoprotein (designated pp83) by PAP was uniformly observed in all cells/tissues of prostate origin, and was completely inhibited by L(+)-tartrate, the classic inhibitor of PAP. Phosphoamino acid analysis revealed that pp83 was a tyrosine-poor phosphoprotein and was mostly dephosphorylated by PAP at serine/threonine residues rather than tyrosine residues. Further comparison of dephosphorylation rate with that of an endogenous phosphotyrosine-containing phosphoprotein (pp53) revealed that PAP possessed both phosphoserine/threonine protein phosphatase and phosphotyrosine protein phosphatase activity. These results demonstrate that pp83 apparently is an endogenous substrate of PAP in human prostate, and that, instead of a phosphotyrosine protein specific phosphatase, PAP is a universal protein phosphatase hydrolyzing equally well the phosphotyrosine, serine, and threonine residues.

Topics: Acid Phosphatase; Humans; Hydrogen-Ion Concentration; Hydrolysis; Male; Phosphoprotein Phosphatases; Phosphoproteins; Phosphorylation; Phosphotyrosine; Prostate; Prostatic Neoplasms; Substrate Specificity; Tumor Cells, Cultured; Tyrosine

To study the significance of prostatic acid phosphatase (PAP), gamma-seminoprotein (gamma-Sm) and prostatic specific antigen (PA) in urine, we have determined the urinary levels of these proteins in women and infants, in patients without prostatic disease, in patients with benign prostatic hypertrophy, and in patients with prostatic adenocarcinoma. Women and infants were found to excrete little PAP (27.9 +/- 4.8 ng/mg) and undetectable levels of gamma-Sm except one case, and undetectable levels of PA in the urine. The excretion of PAP in patients with prostatic carcinoma who were either castrated, or treated with endocrine therapy was lower than the levels in women and infants, or the levels in patients without prostatic diseases, or the levels in patients with BPH. Urinary excretion levels of gamma-Sm and PA were undetectable in the patients with well-controlled prostatic carcinoma. The present study suggests that the determination of PAP, gamma-Sm and PA in the urine of patients with prostatic carcinoma may become a useful tool for monitoring of the primary locus of the carcinoma, but additional assays of urinary PAP, gamma-Sm and PA should be measured at regular intervals to be concluded.

Topics: Acid Phosphatase; Adenocarcinoma; Adolescent; Adult; Aged; Aged, 80 and over; Antigens, Neoplasm; Biomarkers, Tumor; Child; Child, Preschool; Female; Humans; Male; Middle Aged; Prostate; Prostate-Specific Antigen; Prostatic Diseases; Prostatic Hyperplasia; Prostatic Neoplasms; Prostatic Secretory Proteins; Proteins; Seminal Plasma Proteins

Health examination - screening: Tumour markers in serum are of minor value when used for detection of the disease in health screening protocols. Reflection of the course of disease: Tumour markers are of great value for monitoring the response to a given therapy and for early detection of relapse. In recent years, measurements of PSA has replaced PAP for this purpose. Prognostic indicator: Tumour markers in serum may also be used to indicate the biological activity of the tumour. Also for this purpose PSA appears to be a more reliable marker than PAP. General recommendation: For newly detected cases of prostatic carcinoma determination of a limited number of prognostic markers is recommended. If no treatment is instituted all these determinations may be repeated at an interval of about one year. Once treatment has been instituted assay of serum markers may be restricted to PSA alone and may be carried out at about six-monthly intervals. In protocolled clinical trials the intervals may be shortened.

Topics: Acid Phosphatase; Antigens, Neoplasm; Biomarkers, Tumor; Humans; Male; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms

Prostate specific acid phosphatase (PAP) (Abbott, solid-phase enzyme immunoassay) and prostate specific antigen (PSA) (Hybritech, immunoradiometric assay) were determined in 162 newly diagnosed prostatic carcinoma patients, 187 patients with benign prostatic hyperplasia (BPH) and 127 controls. The upper limit of normal in controls for PAP was 2.2 micrograms/l and for PSA 5.0 micrograms/l. In the BPH group PAP was raised in 21%, for PSA in 41%. When the cut-off level of PSA was raised to 10.0 micrograms/l, 20% of BPH patients had an increased level. PSA was superior to PAP for the detection of prostatic cancer in all stages. Of the 162 patients with prostatic carcinoma, 88 had localised diseases and 74 had metastatic spread. PSA and PAP levels increased with each advancing clinical stage. PAP was elevated in 35% of the patients with cancer confined to the prostate. PSA in 69%. (PSA level 10.0 micrograms/l: 57%). In those patients with metastatic spread PAP was elevated in 77% compared with 96% for PSA. (PSA level 10.0 micrograms/l: 92%). The combined use of PSA and PAP does not give a greater accuracy in the screening of prostate cancer when compared with the sole use of PSA. PAP was elevated in only 4 patients when PSA was normal. In the BPH group there was no proven effect of micturition, frequency or residual urine on the SPA level. However, in this group infection may cause a rise in the PSA level.

Topics: Acid Phosphatase; Aged; Aged, 80 and over; Antigens, Neoplasm; Biomarkers, Tumor; Diagnosis, Differential; Humans; Male; Middle Aged; Prostate; Prostate-Specific Antigen; Prostatic Hyperplasia; Prostatic Neoplasms

Eleven male patients with pelvic malignancy underwent laparoscopic lymphadenectomy for staging of their tumors. The technique allowed removal of pelvic lymph nodes in all 11 patients and metastatic disease was found in five cases, resulting in a change of recommended therapy. The technique was via a three-port exposure, although a fourth suprapubic port was occasionally used for additional retraction. A bladder laceration, which was repaired laparoscopically, was the only intraoperative complication. A pelvic hematoma was the only significant postoperative complication. Laparoscopic pelvic lymphadenectomy appears to offer a less morbid staging for those patients with a high likelihood of nodal metastasis. Laparoscopic detection of positive pelvic lymph nodes may alter the management of genitourinary malignancy and improve overall patient care.

Topics: Acid Phosphatase; Aged; Biopsy, Needle; Dissection; Electrocoagulation; Humans; Intraoperative Complications; Laparoscopes; Laparoscopy; Lymph Node Excision; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Staging; Pelvis; Pneumoperitoneum, Artificial; Posture; Prostate-Specific Antigen; Prostatic Neoplasms; Therapeutic Irrigation; Urinary Bladder Neoplasms; Video Recording

Bone alkaline phosphatase (b-ALP) and tartrate resistant acid phosphatase (tr-ACP) are markers of the activity of osteoblasts and osteoclasts, respectively. We have already shown that the serum activity of these isoenzymes was elevated in breast cancer patients with bone metastasis (BM); we show here that the serum activity of b-ALP and tr-ACP were also elevated in prostate cancer patients with BM. Specificity and sensitivity of b-ALP for BM were 0.90 and 0.75, respectively; and for tr-ACP, 0.60 and 0.60, respectively. The accuracy of b-ALP as a BM marker was higher than the accuracy of usual markers of prostatic carcinoma (tartrate labile ACP [tl-ACP], prostatic acid phosphatase [PAP] and prostate specific antigen [PSA]). The highest value predictive of a positive bone scan was obtained with b-ALP (0.88); this increased to 0.97 when b-ALP was coupled with PAP.

Topics: Acid Phosphatase; Alkaline Phosphatase; Biomarkers, Tumor; Bone Neoplasms; Humans; Isoenzymes; Male; Prostatic Neoplasms

Twenty-nine consecutive patients with localized prostatic carcinoma were studied prospectively to assess the effect of radical pelvic irradiation on the serum prostatic acid phosphatase level (SPAPL). The doses of radiation given ranged from 64.00 to 66.00 Gy. SPAPLs were taken before, during and shortly after their treatment. No significant individual variations in SPAPLs were found. When patients with prostatic carcinoma show rises in serum prostatic acid phosphatase during or after pelvic irradiation, these are unlikely to be due to their treatment and occult pelvic nodal or bony disease should be considered.

Topics: Acid Phosphatase; Humans; Male; Prostate; Prostatic Neoplasms

We have evaluated the effects of tumour mass and circulating antigen (prostatic acid phosphatase, PAP) on the biodistribution and the incorporation of 111In-labelled F(ab')2 monoclonal antibody (MoAb) fragments directed against human PAP into human prostatic tumours (PC-82; 0.1-8.9 g) growing in nude mice. The radioactivities in the blood, liver, spleen, kidney and tumour were compared at 1, 3, 4 and 6 days after the intravenous administration of the antibody fragments. There was a significant correlation between the tumour size and the serum PAP concentration in the model employed. Even tissue of a small tumour (less than 0.1 g) had a high concentration of PAP, but it was not secreted into the circulation in detectable amounts when measured by radioimmunoassay (the lowest standard was 0.5 micrograms/l). The percentage uptake by tumours of the injected dose per gram of tissue (%ID/g) was inversely proportional to the tumour size at 24 h after the administration of 111In-labelled F(ab')2 fragments. This relationship had levelled off by 72 h and most likely reflected a better vascularisation of the smaller tumours. Our results show that the increase in tumour size and in the concentration of circulating antigen in the blood led to decreased tumour-to-blood ratios, since there was a tendency for higher blood activities in mice with larger tumours and higher serum PAP concentrations. There was no correlation between tumour size and label uptake by the liver during the follow-up over 144 h, although serum PAP concentrations ranged from 3.1 micrograms/l to 352 micrograms/l.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acid Phosphatase; Adenocarcinoma; Animals; Antibodies, Monoclonal; Humans; Immunoglobulin Fab Fragments; Immunoglobulin Fragments; Indium Radioisotopes; Male; Mice; Mice, Nude; Prostate; Prostatic Neoplasms; Transplantation, Heterologous

To determine whether prostatic acid phosphatase (PAP) immunoreactivity in prostatic adenocarcinoma is a reliable prognostic factor, the PAP immunohistochemical distribution has been examined in 78 prostatic carcinoma cases. The intensity of PAP immunostaining was graded from 0 to 2, and the scores of the primary and the secondary staining patterns were added to assess the extent of the PAP expression in needle biopsy specimens. As a result, a higher cancer-specific survival rate was observed in patients showing a greater PAP immunostaining (P less than 0.01). Further, a multivariate analysis was made of possible prognostic factors (age, stage, Gleason score, serum PAP, PAP-immunostaining score, and the initial treatment) to estimate the extent of their impact on cancer-specific survival. Results have confirmed that the difference in PAP immunoreactivity is an excellent, independent prognostic factor for prostatic carcinoma.

Topics: Acid Phosphatase; Adenocarcinoma; Aged; Aged, 80 and over; Epithelium; Humans; Immunohistochemistry; Male; Middle Aged; Multivariate Analysis; Neoplasm Staging; Prognosis; Prostate; Prostatic Neoplasms

Topics: Acid Phosphatase; Adult; Carcinoid Tumor; Humans; Male; Prostate; Prostatic Neoplasms

The value of routine bone scans as a staging procedure was assessed in patients with newly diagnosed prostate cancer. Records from 277 patients were reviewed retrospectively to determine the serum acid and alkaline phosphatases, the presence or absence of bone pain, and the results of bone scans and other radiographic studies at the time of initial diagnosis. We determined the sensitivity and specificity of an abnormal acid phosphatase, an abnormal alkaline phosphatase, and the presence of bone pain used in combination for assessing bone metastases. If at least one of these three parameters was present, the sensitivity was 97 percent, whereas if all three tests were normal, the specificity was 78 percent. The negative predictive value for all three tests combined is 99 percent. These results suggest that a routine bone scan to stage patients with newly diagnosed prostate cancer who have no bone pain and normal acid and alkaline phosphatases may not be warranted in all cases.

Topics: Acid Phosphatase; Adult; Aged; Aged, 80 and over; Alkaline Phosphatase; Biomarkers, Tumor; Bone Neoplasms; Humans; Male; Middle Aged; Neoplasm Staging; Predictive Value of Tests; Prostatic Neoplasms; Radionuclide Imaging; Retrospective Studies

This report concerns the study of the relationship between protein expression and the cell cycle in exponentially proliferating benign and malignant human prostate epithelial cells in short-term cultures. Multiparameter flow cytometric measurements were performed to correlate the expression of prostate-specific acid phosphatase, epithelial membrane antigen and epitectin with cell cycle progression. The expression of the three proteins was heterogeneous in G1 cells. The early post-mitotic cells exhibited the lowest levels when compared with late G1 cells, wherein the expression was many times greater. There was no further increase as the cells progressed through S and G2 + M. These findings, corroborating prior observations in other systems, suggest the possibility that the levels of the proteins studied increase during the G1 phase of the cell cycle and drop during or immediately after cytokinesis. As an alternate explanation, the heterogeneity of protein expression characteristic of G1 cells may be due, at least in part, to an asymmetric apportionment of cell constituents at mitosis.

Topics: Acid Phosphatase; Antigens, Tumor-Associated, Carbohydrate; Cell Cycle; Cell Division; Cells, Cultured; Epithelial Cells; Epithelium; Flow Cytometry; Fluorescent Antibody Technique; Humans; Kinetics; Male; Membrane Glycoproteins; Mucin-1; Prostate; Prostatic Neoplasms; Protein Biosynthesis; Tumor Cells, Cultured

Of 438 consecutive cases of newly diagnosed prostate cancer, 178 (41%) had skeletal metastases (T0-4 M1) at the time of diagnosis according to skeletal scintigraphy; 139 men had serum prostatic acid phosphatase (PAP) greater than twice the upper limit of normal on 2 separate occasions at the time of diagnosis and 65% of them had metastases on bone scan. However, 49 men with normal bone scans were found to have similarly raised serum PAP. (Such patients are defined as having skeletal metastases in the current Medical Research Council immediate versus deferred orchiectomy study and stratified accordingly). The actuarial survival of this group was calculated by life table methods and was compared with that of 2 other subgroups: those patients having metastases demonstrated on bone scan, and those patients having both normal bone scans and normal serum PAP. The survival of the "metastatic by acid phosphatase" group was significantly better than that of the "metastatic by bone scan" group but did not differ from that of patients having both normal scans and PAP. For patients with no scintigraphic evidence of skeletal metastases at diagnosis, those with a raised PAP were at a significantly greater risk of scan conversion, although this was more powerfully predicted by high histological grade.

Topics: Acid Phosphatase; Bone and Bones; Bone Neoplasms; Humans; Male; Prognosis; Prostatic Neoplasms; Radionuclide Imaging; Survival Rate

Simultaneous hourly changes in serum PSA and PAP levels per twenty-four-hour period was studied in 19 urologic patients with no prostatic disease. Serum PSA was determined using Hybritech PSA-R Kits, and PAP was determined using EIA method. PSA and PAP serum levels varied independently from each other. PSA level showed no diurnal variations. The level remained stable with minor variations around a low mean of 0.907 ng/mL, SD 0.09, and CV 9.9% in 16 of 19 (84%) patients, while PAP showed changes consistent with diurnal variations in 5 of those patients. Random variations with no discernible pattern in 7 and remained more or less constant in 4 other patients. Marked random variations in PSA serum level occurred in only 3 patients in the older age group and were accompanied by diurnal variations in PAP level in 2 patients and a constant high level of PAP in 1 patient. The highest PSA level obtained was 6.9 ng/mL which is important when selecting the cut-off level. PSA did not increase appreciably after prostatic massage, and on follow-up PSA returned to premassage level after twenty-four hours (except in 1 patient).

Topics: Acid Phosphatase; Adult; Aged; Antigens, Neoplasm; Biomarkers, Tumor; Circadian Rhythm; Humans; Immunoenzyme Techniques; Male; Middle Aged; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Reagent Kits, Diagnostic; Time Factors

A fragment of a complementary DNA (cDNA) clone for human prostatic acid phosphatase (PAP) (EC 3.1.3.2.) was used to study the expression of corresponding mRNA in human tissues. The specificity of its expression in benign prostatic hyperplasia (BPH) and prostatic carcinoma tissues were indicated in RNA blot analyses. The PAPcDNA probe did not recognize any specific mRNAs in RNAs extracted from human liver cancer, lung cancer, pancreatic cancer, placenta, breast cancer cells (MCF-7), mononuclear blood cells or acute promyelocytic leukemia cells (HL-60), according to Northern blot analysis. mRNA for PAP was detected in the androgen-dependent human prostatic cancer cell line LNCaP, but not in the androgen-insensitive human prostatic cancer cell line PC-3. In contrast, lysosomal acid phosphatase (LAP) mRNA was detected in both of these human prostatic cancer cell lines. Our findings indicate a high specificity for the PAP gene in prostatic tissue. The mean abundance for the PAPmRNA expression was 0.26 for prostatic carcinoma samples (n = 11) and 0.46 for BPH samples (n = 8) according to slot-blot analysis. The differences observed between the different categories of prostatic tissue in PAPmRNA abundances call for additional studies on regulation of its expression.

Topics: Acid Phosphatase; Blotting, Northern; Cell Line; DNA Probes; Gene Expression; Humans; Male; Nucleic Acid Hybridization; Prostate; Prostatic Neoplasms; Radioimmunoassay; RNA; Substrate Specificity; Tumor Cells, Cultured

Topics: Acid Phosphatase; Adenocarcinoma; Aged; Aged, 80 and over; Antigens, Neoplasm; Biomarkers, Tumor; Glomerulonephritis; Humans; Immunoenzyme Techniques; Male; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Staining and Labeling

We used the method of Rudolph et al. (Clin Chem 1988; 34:2031-8) to find information in the data from correlated determinations of acid phosphatase (PAP, EC 3.1.3.2; DuPont aca) and prostate-specific antigen (PSA, Hybritech). We described there how we assign medical decision limits for two or more correlated variables and convert the database to a binary coded message, allowing separation of a selected disease class with minimum error. The decision point, analogous to a percentile upper limit on the ordered values of each variable in the reference group, satisfies the maximum entropy constraints of reference, producing a minimum entropy for the binary coded patient database. We found maximum entropy decision points at PAP = 0.75 U/L and PSA = 22.8 micrograms/L. Patients with PSA values exceeding 22.8 micrograms/L had no benign prostatic disease except for five patients with benign prostate hyperplasia (BPH) with adjacent colon carcinoma (95.3), BPH with infarction (27.6), BPH (23.4) 28.1), or acute prostatitis (34.6). We consider PSA exceeding 22.8 micrograms/L as indicative of carcinoma of the prostate, stage C or D, in the absence of disconfirming evidence. Another decision value for PSA is 11.3 micrograms/L. This bounds the region between 11.3 and 22.8 micrograms/L, where the frequency of BPH is 1.5 times that for adenocarcinoma. At PSA less than 11.3 micrograms/L there is a high frequency of BPH. PSA concentration is not correlated with prostatic size (mass) or with prostatitis. A metastatic carcinoma is as likely to be nonprostatic as prostatic when the PSA concentration is less than 11.3 micrograms/L.

Topics: Acid Phosphatase; Adenocarcinoma; Antigens, Neoplasm; Biomarkers, Tumor; Humans; Male; Middle Aged; Prostate-Specific Antigen; Prostatic Hyperplasia; Prostatic Neoplasms; Prostatitis; Risk Factors; Statistics as Topic

A mucinous adenocarcinoma of the prostate is rate, and a doubtful diagnosis should be verified to determine that the tumor surely does arise from the prostate, since a mucinous adenocarcinoma arising from the gastrointestinal tract is not as rare and often metastasizes to the prostate. We herein report on a case of a mucinous adenocarcinoma of the prostate, the origin of which was proved to be the prostate by immunohistochemical staining for a prostate-specific antigen and prostate-specific acid phosphatase.

Topics: Acid Phosphatase; Adenocarcinoma, Mucinous; Aged; Antigens, Neoplasm; Clinical Enzyme Tests; Humans; Immunohistochemistry; Male; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms

Serum acid phosphatase activity (ACP), prostate specific phosphatase (PAP) and prostate specific antigen (PSA) were measured in 100 patients with prostatic cancer. The patients were divided into 4 groups: T1-2 MO, T3-4 MO and M1 patients with less than or equal to 10 or greater than 10 metastatic foci in bone scintigraphy. The mean serum ACP levels were almost identical in the T1-2 MO and T3-4 MO groups and there was no significant difference between the mean PAP values. Significantly higher PSA levels were observed in the MO patients in the extracapsular category compared with those in the intracapsular category. The mean serum levels of all 3 tumour markers were significantly higher in the M1 than in the MO category. PSA seems to be the marker of choice as a diagnostic aid for differentiating between patients with intracapsular and those with extracapsular tumour growth. In prostatic cancer patients with bone metastases these markers were of similar value for staging the disease.

Topics: Acid Phosphatase; Aged; Aged, 80 and over; Antigens, Neoplasm; Biomarkers, Tumor; Humans; Male; Middle Aged; Neoplasm Staging; Prostate-Specific Antigen; Prostatic Neoplasms

The introduction of new tumours markers poses the problem of assessing their real predictive power and of considering all their possible uses. The following questions have been examined: 1) is PSA able to offer early diagnosis of prostate Ca 2) is there a relationship between cancer grading and PSA levels? 3) is it possible to use PSA to monitor patients under treatment? 4) can PSA predict the existence of bone metastasis?

Topics: Acid Phosphatase; Adenocarcinoma; Antigens, Neoplasm; Biomarkers, Tumor; Bone Neoplasms; Humans; Male; Monitoring, Physiologic; Neoplasm Staging; Prognosis; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Radioimmunoassay

Twelve patients with primary mucinous adenocarcinoma of the prostate were included in a clinicopathologic study; criteria included a total tumor volume more than 25% mucinous and single or clustered tumor cells floating in mucin lakes. Patient ages were 57 to 81 years; tumor stages were C (three), D (five), and unknown (four). Bone was the most frequent metastatic site (usually osteoblastic), followed by lymph nodes and lungs. Serum levels of prostatic acid phosphatase and prostate-specific antigen were frequently elevated (five of 10 and three of three measured, respectively). All mucinous adenocarcinomas also contained other histologic patterns: microglandular (four), cribriform (three), comedo (two), solid (two), and hypernephroid (one). Mucinous components composed less than 50% of three tumors, 50% and 75% of six, and more than 75% of three. No tumor contained signet-ring cells. Immunoperoxidase staining was positive for prostatic acid phosphatase and prostate-specific antigen and negative for carcinoembryonic antigen. Treatment was radiation, estrogen, orchiectomy, or a combination. In two of four patients, serum prostatic acid phosphatase levels normalized after therapy. Seven patients died of disease (mean follow-up, 56 months), and five patients are alive with disease (mean, 32.2 months). The proportion of mucinous component did not affect prognosis.

Topics: Acid Phosphatase; Adenocarcinoma, Mucinous; Aged; Aged, 80 and over; Antigens, Neoplasm; Carcinoembryonic Antigen; Histocytochemistry; Humans; Immunohistochemistry; Male; Middle Aged; Mucins; Prostate-Specific Antigen; Prostatic Neoplasms

Serum levels of gamma-seminoprotein (GSM), prostate specific antigen (PSA) and prostate specific acid phosphatase (PAP) were examined, using enzyme immunoassay, in 250 patients with prostatic disease. The results indicated that the highest specificity was obtained with GSM (94%) and the lowest with PSA (60%). In contrast, the highest sensitivity in newly detected carcinomas (n = 41) was obtained with PSA (71%), whereas that of GSM (51%) was comparable to that of PAP (44%). Of 41 patients with newly detected prostatic cancer, 35 (85%) showed a significant increase in at least 1 of the tumour markers. Five of 6 patients whose markers were within normal limits had incidental carcinomas. During follow-up, PSA was raised in 88%, GSM in 66% and PAP in 55% within 12 months prior to clinical progression. Our results suggest that the determination of GSM may be of value in the serological detection and monitoring of prostatic cancer. These findings must be confirmed by further studies with larger numbers of patients and longer follow-up.

Topics: Acid Phosphatase; Antigens, Neoplasm; Biomarkers, Tumor; Humans; Male; Pilot Projects; Prognosis; Prostate; Prostate-Specific Antigen; Prostatic Hyperplasia; Prostatic Neoplasms; Prostatic Secretory Proteins; Proteins; Seminal Plasma Proteins; Testicular Hormones

The role of prostate-specific antigen (PSA), a sensitive tumor marker for cancer of the prostate, has yet to be defined in patients treated with radiotherapy. To evaluate this, PSA and acid phosphatase (AP) were measured prospectively in 110 sequential patients who presented with locoregional carcinoma of the prostate and in whom radiotherapy was to be definitive treatment. Therapy was divided into the following treatment groups: external-beam radiotherapy alone (EBRT), EBRT with brachytherapy (EBRT + B), and hormone therapy either pre-EBRT or post-EBRT (EBRT + H). All patients have been followed for 1 to 17 months and a total of 521 posttreatment PSA determinations have been made. In 91 of 110 patients (83%) PSA was elevated pretreatment and correlated with clinical stage and subsequent relapse. There was no association with Gleason grade, assigned treatment group, or lymph node involvement. Acid phosphatase was elevated in only 31% of the patients initially and had no predictive value in subsequent failure. Nine patients have developed local and/or distant recurrence. None of the patients who failed had their PSA return to normal whereas 74 of 101 (73%) of the remainder have done so. Levels of PSA that do not return to normal during follow-up probably indicate active disease, often without evidence of clinical relapse. The authors conclude that PSA is a useful tumor marker for monitoring response to radiotherapy and may be a predictor of eventual failure thus identifying patients eligible for early intervention therapy as and when it becomes available.

Topics: Acid Phosphatase; Aged; Aged, 80 and over; Antigens, Neoplasm; Biomarkers, Tumor; Brachytherapy; Buserelin; Follow-Up Studies; Goserelin; Humans; Male; Middle Aged; Prognosis; Prostate-Specific Antigen; Prostatic Neoplasms

Systematic screening for prostate cancer was carried out in 600 men over 50 years of age by the industrial medicine departments of four big companies in the Paris region. The exploratory methods included prostate specific antigen (PSA) and prostatic acid phosphatase (PAP) assays, rectal palpation and two-dimensional transrectal ultrasonography. Biopsy of the prostate was performed either when the PSA level was above 5 ng/ml or when rectal palpation gave suspicious results, or when ultrasonography showed abnormal images. A total of 93 biopsies were performed, and 18 cases of cancer were detected. Eleven of these 18 patients underwent radical prostatectomy. The PSA assay, with an accepted limit of 5 ng/ml, detected 17 out of 18 cancers but was not very specific. The PAP assay had low sensitivity (only 5 positive results). Combined PAP assay and rectal palpation provided high sensitivity and good specificity. Transrectal ultrasonography was helpful only to determine the site of biopsy and the distribution of the lesions.

Topics: Acid Phosphatase; Aged; Aged, 80 and over; Antigens, Neoplasm; Biopsy, Needle; Humans; Male; Middle Aged; Neoplasm Staging; Physical Examination; Prostate-Specific Antigen; Prostatic Neoplasms; Rectum; Ultrasonography

We used fine needle biopsies from prostatic tumors at routine examinations in 133 patients. Cytological grading was performed with a scoring system. Cellular prostatic acid phosphatase and cellular prostate specific antigen from the aspirates were quantitated. Deoxyribonucleic acid flow cytometry was performed and the tumors were subdivided into diploid, tetraploid and aneuploid groups. Tumor staging was assessed by digital examination. A decrease in the biochemical markers was significantly correlated with the increase in malignancy grade, tumor stage and a shift from diploid to aneuploid tumors. Cellular prostatic acid phosphatase and cellular prostate specific antigen as well as tumor ploidy may contribute to the objective determination of the malignancy potential of the prostatic carcinoma.

Topics: Acid Phosphatase; Antigens, Neoplasm; Biomarkers, Tumor; Biopsy, Needle; Carcinoma; DNA, Neoplasm; Flow Cytometry; Humans; Male; Ploidies; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms

We are interested in the therapeutic response to chemotherapy and radiotherapy of relapsed prostate cancer. In 9 cases of prostate cancer treated by endocrine therapy, tumor markers (PAP.PA.gamma-Sm.Leu-7) and cell types at the start of endocrine therapy and that taken at a hormone independent point were compared between prostatic tissue obtained. All cases had a period of response to endocrine therapy, but subsequently relapsed. The results were divided into the following 3 groups: Group I (changed cell type.decreased positive rate of markers) had the shortest response duration to endocrine therapy and there was no response to chemotherapy; Group II (unchanged cell type.decreased positive rate of markers) had a long response duration and slow progression under endocrine therapy; Group III (unchanged cell type.unchanged positive rate of markers) was chemo- or radiotherapy sensitive during post-endocrine therapy relapse. These results suggest that this is an effective method which dictated the choice of treatment method and allowed an approximate prognosis for relapsed prostate cancer previously treated by endocrine therapy.

Topics: Acid Phosphatase; Aged; Aged, 80 and over; Antigens, Differentiation; Biomarkers, Tumor; CD57 Antigens; Combined Modality Therapy; Diethylstilbestrol; Gonadotropin-Releasing Hormone; Humans; Male; Middle Aged; Neoplasm Staging; Orchiectomy; Prostatic Neoplasms; Prostatic Secretory Proteins; Proteins; Recurrence; Seminal Plasma Proteins

We measured prostatic acid phosphatase (PAP), gamma-seminoprotein (gamma-Sm) and prostatic specific antigen (PSA) levels simultaneously in the serum of 52 patients with untreated prostatic cancer and 44 patients with benign prostatic hypertrophy to assess the clinical usefulness of these tumor markers. PAP and PSA were measured by radioimmunoassay and gamma-Sm by enzyme immunoassay. The positive rates of PAP, gamma-Sm and PSA in patients with prostatic cancer were 50.0, 61.5 and 69.2%, respectively, and those in patients with benign prostatic hypertrophy were 11.4, 13.6 and 13.6%, respectively. In patients with early stage prostatic cancer (stage A and B), the positive rates of PAP, gamma-Sm and PSA were 20.8, 41.7 and 54.2%. The efficiency of PSA was the highest among the three markers. The positive rate of the combination assay of PAP and PSA, that of gamma-Sm and PSA and that of PAP, gamma-Sm and PSA were slightly higher than that of the PSA assay alone. However, the efficiency of the PSA assay alone was higher than that of any combination. No significant correlation was found between histopathological grade and the level of each tumor marker. A significant correlation was found between PAP and gamma-Sm (r = 0.68, P less than 0.001), and between PAP and PSA (r = 0.61, P less than 0.001), but there was no correlation between gamma-Sm and PSA. These results suggest that PSA is the most useful marker and the combination assay of multiple markers is not so advantageous, at least for screening of prostatic cancer.

Topics: Acid Phosphatase; Aged; Aged, 80 and over; Antigens, Neoplasm; Biomarkers, Tumor; Clinical Enzyme Tests; Humans; Male; Middle Aged; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Prostatic Secretory Proteins; Proteins; Seminal Plasma Proteins

Analytical and clinical evaluations were made on the measurement of prostatic acid phosphatase (PAP) and prostate specific antigen (PA) by a fully automated enzyme immunoassay system. Results concerning reproducibility, recovery and sensitivity were good. PAP values by this method correlated well with those obtained by radioimmunoassay. PA values by this method were higher than those obtained by other enzyme immunoassays, although the correlation coefficient was high. PAP, PA and gamma-Seminoprotein (gamma-Sm), another prostatic tumor marker, were all poorly correlated to one another. Normal upper value, 2 SD of 720 healthy males was 1.2 ng/ml for PAP, and 3.7 ng/ml for PA. Positive ratios of these tests in 31 patients with prostatic carcinoma were high at advanced stages, and low at early stages. ROC (receiver operating characteristics) curve analysis on patients with prostatic carcinoma and benign prostatic hypertrophy indicated that PAP and PA were more effective than gamma-Sm for the differential diagnosis of prostatic carcinoma, and that the clinical cut off was 2.0 ng/ml for PAP, 7.4 ng/ml for PA and 4.0 ng/ml for gamma-Sm.

Topics: Acid Phosphatase; Adult; Aged; Antigens, Neoplasm; Biomarkers, Tumor; Humans; Immunoenzyme Techniques; Male; Middle Aged; Prostate-Specific Antigen; Prostatic Neoplasms

We developed an assay to measure at acid pH the phosphotyrosine phosphatase activity in sera from patients with prostatic cancer. The method used quantifies the inorganic phosphate liberated from phosphotyrosine after incubation with serum, followed by the deproteinization of the reaction mixture. A high acid phosphatase (EC 3.1.3.2) activity towards phosphotyrosine was observed in all sera from patients with increased activity of prostatic acid phosphatase. This activity represented 96% of prostatic acid phosphatase and 77% of total acid phosphatase activities. Moreover, it was correlated (r = 0.91) with the amount of serum prostatic acid phosphatase determined by radioimmunoassay. When serum acid phosphatase activity was measured on several phosphorylated substrates, preferential hydrolysis was demonstrated for those in which the phosphate group was esterified on an aromatic ring rather than those presenting an aliphatic chain. Among phosphoamino acids, only phosphotyrosine was a good substrate, with little or no activity observed with phosphoserine and phosphothreonine. Human seminal plasma and partially purified prostatic acid phosphatase, tested for their activity on some of these substrates, gave similar results. On the other hand, sera from patients with above-normal alkaline phosphatase activity and no prostatic disease showed little or no activity on phosphotyrosine at both acid and alkaline pH values. Evidence is presented that the prostatic acid phosphatase in serum is a specific phosphotyrosine acid phosphatase.

Topics: Acid Phosphatase; Alkaline Phosphatase; Humans; Hydrogen-Ion Concentration; Kinetics; Male; Phosphoprotein Phosphatases; Phosphotyrosine; Prostatic Neoplasms; Protein Tyrosine Phosphatases; Reproducibility of Results; Semen; Tyrosine

Serum acid phosphatase levels were determined in 247 men with surgically confirmed intracapsular prostatic cancer (30 patients), benign prostatic hyperplasia (BPH) (114 patients) or palpably normal prostates (103 men). Both radioimmunoassay (245 cases) and an enzymatic method (218 cases) were used. Using radioimmunoassay, the mean serum prostatic acid phosphatase (PAP) level was significantly higher in patients with BPH than in patients with intracapsular cancer or men with normal prostates. The weight of hyperplastic tissue removed during operation in the BPH group correlated closely with PAP concentrations. Age or the presence (or absence) of an indwelling catheter had no effect on PAP concentration. Using the enzymatic method, the highest levels of acid phosphatase were also detected in patients with BPH but the difference was less marked. It was concluded that intracapsular cancer does not elevate serum acid phosphatase levels as determined by radioimmunoassay or an enzymatic method. BPH alone leads to significant rises in PAP concentrations. The degree of BPH correlates with PAP levels.

Topics: Acid Phosphatase; Adolescent; Adult; Aged; Aged, 80 and over; Clinical Enzyme Tests; Humans; Male; Middle Aged; Prostatic Hyperplasia; Prostatic Neoplasms; Radioimmunoassay; Reference Values

The correlation of technetium-99m-HMDP bone scintigraphic findings, serum osteocalcin as a measure of bone turnover and prostate-specific antigen (PSA) and/or prostate acid phosphatase (PAP) was determined in 19 men with bone metastasis due to prostatic carcinoma. Six of the 19 patients with metastases on bone scan showed elevation of osteocalcin. These patients had extensive metastatic disease. All 19 men with positive bone scans had high serum PSA and/or PAP levels. Serum osteocalcin measurement is less sensitive to detection of bone deposits than PSA/PAP measurements (p less than 0.0008).

Topics: Acid Phosphatase; Aged; Antigens, Neoplasm; Biomarkers, Tumor; Bone and Bones; Bone Neoplasms; Humans; Male; Middle Aged; Osteocalcin; Prostate-Specific Antigen; Prostatic Neoplasms; Radionuclide Imaging; Technetium Tc 99m Medronate

A comparison is made of prostatic acid phosphatase (PAP) and prostate specific antigen (PSA) in the diagnosis of prostatic carcinoma. In a retrospective study PAP ans PSA were compared in 127 normal elderly men, in 187 patients with benign prostatic hyperplasia (BPH) and in 162 patients with untreated prostatic carcinoma. In the control group a normal value of 2.2 micrograms/l was found for PAP and 5.0 micrograms/l for PSA. In 41% of BPH patients the PSA level was higher than 5.0 micrograms/l. Because of this substantial percentage a cut-off value of 10 micrograms/l was used instead of 5.0 micrograms/l. In the BPH group 20% had a PSA level over 10 micrograms/l and 21% a PAP over 2.2 micrograms/l. Of the carcinoma patients without metastasis 57% had a PSA level over 10 micrograms/l and of those with metastatic disease, 92%. For PAP these percentages were 35 and 77, respectively. It is concluded that PSA is a more sensitive tumour marker than PAP.

Topics: Acid Phosphatase; Aged; Antigens, Neoplasm; Biomarkers, Tumor; Humans; Male; Middle Aged; Prostate-Specific Antigen; Prostatic Hyperplasia; Prostatic Neoplasms; Retrospective Studies; Sensitivity and Specificity

In 35 patients with histologically confirmed carcinoma of the prostate confined to the pelvis, the value of prostate-specific antigen (PSA) was evaluated during external beam radiotherapy to the prostate and draining pelvic lymph nodes. In eleven patients initial prostate-specific antigen levels were more than 10 ng/ml and in twelve patients between 4 and 10 ng/ml. In the remaining twelve, initial prostate-specific antigen levels were less than 4 ng/ml. In the course of radiotherapy we could see a significant decrease of the prostate-specific antigen, even in those with levels between 4 and 10 ng/ml. This decrease seems to follow a logarithmic course but, because only three measurements during radiotherapy were made, this needs further study. With higher levels (more than 20 ng/ml), we rarely saw a value of less than 10 ng/ml at the end of radiotherapy but had to wait for several months for lower values to be reached. In several cases prostate-specific antigen decrease took up to three months after the end of the radiation course. Our results indicate that prostate-specific antigen values actually start decreasing during the radiation course itself and may, therefore, be useful for monitoring response to radiotherapy.

Topics: Acid Phosphatase; Aged; Aged, 80 and over; Antigens, Neoplasm; Biomarkers, Tumor; Carcinoma; Clinical Enzyme Tests; Humans; Male; Middle Aged; Monitoring, Immunologic; Monitoring, Physiologic; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Radiotherapy Dosage; Radiotherapy, High-Energy; Time Factors

A series of 55 randomly chosen radical prostatectomy specimens was analyzed for expression of prostate-specific antigen (PSA) by immunohistochemical techniques. Tissue sections were selected in such a manner that in addition to glandular benign prostatic hyperplasia (BPH), one or more different prostatic tumour growth patterns were present. Four monoclonal antibodies, directed against three different PSA epitopes, and one polyclonal anti-PSA antiserum were used. Expression of PSA was compared with that of prostate-specific acid phosphatase (PAP), recognized by two different polyclonal antisera. A critical dilution aimed at a maximum of staining intensity on BPH tissue sections was chosen for all antibodies. Anti-PSA and anti-PAP antisera stained essentially all BPH samples (over 90%). Irrespective of the nature of the antibodies used, PSA expression was found to be decreased in prostatic carcinoma. A clear cut relationship was found between immunoreactivity for PSA and the degree of differentiation of the tumour area. Under the experimental conditions used the PSA monoclonal antibodies stained only 1 out of 10 undifferentiated carcinomas, whereas 50% to 70% of the well- and moderately-differentiated carcinomas showed immunoreactivity. This correlation was less pronounced with the PAP staining pattern. If the PSA antibody titer was raised the percentage of clearly staining undifferentiated carcinomas could be considerably increased (up to 60%-100%), indicating that PSA expression is not absent, but lowered in most (if not all) undifferentiated carcinomas.

Topics: Acid Phosphatase; Adenocarcinoma; Antigens, Neoplasm; Biomarkers, Tumor; Humans; Immunoenzyme Techniques; Male; Prostate; Prostate-Specific Antigen; Prostatic Hyperplasia; Prostatic Neoplasms

This study examines the relationship between the presence of prostatic acid phosphatase (PAP) and prostate specific antigen (PSA) in tissue, the serum PAP and PSA levels and tumour grade in prostatic adenocarcinoma. Thirty-three tumours were studied by the indirect immunoperoxidase method for PAP and PSA production. Thirty-one of them were stained positive for both markers. The remaining two which previous histopathological studies suggested were transitional cell carcinoma, stained negative. In primary tumours there was a weak trend for poor immunoreactivity in high grade neoplasms but the correlation was not significant. The elevated serum PAP and PSA levels did not correlate with the intensity of staining in the tissue.

Topics: Acid Phosphatase; Adenocarcinoma; Antigens, Neoplasm; Biomarkers, Tumor; Humans; Immunoenzyme Techniques; Male; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Retrospective Studies

Twenty-one cases showing only low Gleason grade prostate carcinoma on needle biopsy were identified. In 15 cases radical prostatectomy was performed with the entire prostate embedded for thorough evaluation of grade, volume, and stage of tumor at the needle biopsy site as well as of multifocal tumor. Eight specimens had solitary low grade and low volume tumor, with only one of these cases showing minimal capsular penetration and the others confined to the prostate. Four cases had low-grade tumor at the biopsy site, yet multifocal higher grade tumor. All of these tumor nodules were low volume and confined to the prostate. In three cases there was both low-grade and high-grade tumor in the nodule sampled by needle biopsy. In two of these cases the tumor was large and in the third it was small but mostly higher grade, with two of these cases showing capsular penetration. Although transrectal ultrasound and repeat needle biopsy would most likely have identified either the tumors' large size or high-grade component in these latter three cases, it is unlikely that these techniques would have identified the cases of multifocal higher grade tumor because of their relatively small size. Furthermore, preoperative serum prostate specific antigen levels and clinical stage failed to distinguish those cases with higher grade tumor. Because of the difficulty in identifying these areas of high-grade tumor preoperatively, it is uncertain whether expectant therapy could be recommended even for patients with very low-grade cancer on needle biopsy.

Topics: Acid Phosphatase; Adenocarcinoma; Antigens, Neoplasm; Biopsy, Needle; Humans; Male; Neoplasm Staging; Prostate-Specific Antigen; Prostatectomy; Prostatic Neoplasms

Thirty-one patients with bidimensionally measurable hormone-refractory prostatic cancer received trimetrexate (TMTX). Serial values of prostate-specific antigen (PSA) and acid phosphatase (SAP) were correlated with response. Five patients (17%; 95% confidence interval, 3% to 30%) achieved a partial remission for a median of 3 months (range, 3 to 7.5 months). Marker levels showed large variations with no discernible patterns. Serial PSA and SAP in 19 patients with abnormal baseline values showed a correlation with measurable disease response in only 68% (13 of 19) and 47% (nine of 19) of patients, respectively. Values were then smoothed using an exploratory data analysis technique of running medians and averages. Trends in marker changes were much more apparent. Several "decision rules" were evaluated for use of markers as indices of disease progression. A 50% increase from the patient's minimum value in either PSA or SAP on two successive determinations correlated with progression in 90% of cases in this trial. TMTX has modest activity in prostatic cancer, and further trials are not warranted. Biochemical markers do not uniformly reflect disease activity in hormone-refractory disease, and changes in biochemical markers must be interpreted cautiously when used as the sole end point to assess efficacy in clinical trials.

Topics: Acid Phosphatase; Aged; Antigens, Neoplasm; Antineoplastic Agents; Biomarkers, Tumor; Humans; Male; Middle Aged; Prostate-Specific Antigen; Prostatic Neoplasms; Quinazolines; Time Factors; Trimetrexate

To examine the role of nerve-sparing radical prostatectomy in patients with clinical stage B2 prostate cancer we reviewed the first 77 such patients in our series since we adopted the nerve-sparing technique. A total of 47 patients (61%) underwent bilateral and 26 (34%) underwent unilateral nerve-sparing prostatectomy, while in 4 (5%) both neurovascular bundles were resected. Among the patients followed for 12 months 27 of 41 (66%) treated with bilateral and 7 of 19 (37%) treated with unilateral nerve-sparing prostatectomy had potency preserved. With the strict clinicopathological criteria of organ-confined tumor, that is intracapsular tumor with negative surgical margins and undetectable postoperative prostate specific antigen levels, complete tumor excision was achieved in 17 patients (36%) treated with bilateral and 7 of 26 (27%) treated with unilateral nerve-sparing prostatectomy. All patients in whom both neurovascular bundles were resected had pathological stage C or D1 disease. Of the 24 patients who had complete tumor excision by the strict criteria only 15 (19.5% of the 77 preoperatively potent patients) had potency preserved. Of these patients 19 had microscopically positive margins without seminal vesicle invasion (pathological stage C1) with undetectable postoperative prostate specific antigen levels. In addition, 4 patients had seminal vesicle involvement with negative surgical margins and undetectable postoperative prostate specific antigen levels. If these patients also are considered as having complete tumor excision, there was an over-all complete tumor excision rate of 61% (47 of 77), of whom 25 (32% of the 77 patients) had preservation of potency. Ten patients with clinical stage B2 tumor whose potency was preserved had histological and serological evidence of incomplete tumor excision. Of 53 patients with pathological stage C1 disease 9 (17%) had margins positive only in the regions of the neurovascular bundles. Preoperative prostate specific antigen and acid phosphatase levels, and findings on transrectal ultrasonography failed to predict accurately which patients had extracapsular tumor extension. Patients with poorly differentiated tumors and/or bulky disease on rectal examination had a higher incidence of extracapsular extension and positive margins. We conclude that in the majority of potent patients with clinical stage B2 prostate cancer not all of the goals of nerve-sparing radical prostatectomy are realized.(ABSTRACT TRUNCATED

Topics: Acid Phosphatase; Aged; Antigens, Neoplasm; Biomarkers, Tumor; Erectile Dysfunction; Humans; Male; Postoperative Complications; Prostate; Prostate-Specific Antigen; Prostatectomy; Prostatic Neoplasms

Topics: Acid Phosphatase; Antigens, Neoplasm; Biomarkers, Tumor; Humans; Male; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms

Prostate-specific antigen (PSA) was measured by polyclonal radioimmunoassay in 45 untreated patients with prostatic cancer and 14 patients with benign prostatic hyperplasia. Prostatic acid phosphatase (PAP) was determined in 35 patients with prostatic cancer and 14 patients with benign hyperplasia. Serum PSA was raised in 42 patients with cancer of the prostate, but only 14 of 35 patients showed increased serum levels of PAP. Half the patients with benign prostate hyperplasia had PSA greater than 4 micrograms/l and one third had PSA greater than 10 micrograms/l. PAP was slightly elevated in two patients with benign prostatic hyperplasia. Serum PSA increased with the clinical stage of prostatic cancer. However, preoperative levels of PSA were not sufficiently reliable to predict the final pathological stage for each individual patient. After radical prostatectomy for cancer confined to the prostate, serum PSA fell to an undetectable level.

Topics: Acid Phosphatase; Adenocarcinoma; Aged; Antigens, Neoplasm; Humans; Male; Prostate-Specific Antigen; Prostatectomy; Prostatic Hyperplasia; Prostatic Neoplasms

Six patients with localized prostatic carcinoma undergoing radical prostatectomy were studied by serial sample collection from the time of surgical removal of the prostate up to one week in the postoperative period. Of the three markers studied (PAP, PSA, LASA), half-life of specific prostatic markers were calculated. Half-life of PAP was found to be 7.25 hours +/- SE of 0.7 hours. For PSA the half-life could be obtained in 4 of 6 patients and was found to be 45.5 hours +/- SE 4.9 hours. In 2 patients PSA did not fall in a regular fashion and half-life could not be obtained. In both patients metastatic disease has developed within six months of surgery. LASA demonstrated progressive increase following surgery, most likely due to associated inflammatory reaction. These studies confirm previous observations that PSA is a more sensitive marker than PAP, and that the presence of an elevated PSA after radical prostatectomy denotes the presence of residual disease.

Topics: Acid Phosphatase; Antigens, Neoplasm; Biomarkers, Tumor; Follow-Up Studies; Half-Life; Humans; Lipids; Male; N-Acetylneuraminic Acid; Neoplasm Staging; Postoperative Care; Prognosis; Prostate-Specific Antigen; Prostatectomy; Prostatic Neoplasms; Sialic Acids

Prostatic acid phosphatase (PAP), gamma-seminoprotein (gamma-Sm) and prostate specific antigen (PSA) were examined on 120 cases of stage D2 prostate cancer between 1979 and 1989. All patients received endocrine therapy as the first treatment; castration and immediate administration of estrogen or antiandrogen (101), LH-RH analogs (13), estrogen (3) and antiandrogen (3). The actuarial survival rates were calculated by the cause-specific survival method. Pretreatment levels of PAP, gamma-Sm and PSA did not influence prognosis. After start of treatment, the relationship between the changes of the markers and prognosis were examined. At 1 month after the start of the treatment, normalization of PAP or gamma-Sm was not reflected in the following course. On the contrary, at 3 and 6 months, groups with normalization of PAP or gamma-Sm showed better prognosis than those with elevated levels. The same tendency of PSA was obtained at 6 months after start of treatment. In patients with normalized PAP at 3 months, abnormal gamma-Sm showed worse prognosis than normalized gamma-Sm. Therefore, the significance of determination on the two markers was manifested. As histological grade influenced the following course, poorly differentiated adenocarcinoma with normalized PAP at 3 months showed better prognosis than those with elevated levels. In conclusion, it is worthwhile to measure multiple markers for predicting the prognosis of stage D2 prostate cancer treated with endocrine therapy.

Topics: Acid Phosphatase; Adenocarcinoma; Aged; Aged, 80 and over; Androgen Antagonists; Antigens, Neoplasm; Biomarkers, Tumor; Estrogens; Gonadotropin-Releasing Hormone; Humans; Male; Middle Aged; Prognosis; Prostate-Specific Antigen; Prostatic Neoplasms; Prostatic Secretory Proteins; Proteins; Seminal Plasma Proteins; Survival Rate

Endobronchial metastases can manifest clinical symptoms and x-ray findings mimicking a centrally located bronchogenic carcinoma. The authors recently encountered a case of endobronchial metastasis from a mucinous adenocarcinoma of the prostate that was originally diagnosed as a primary bronchogenic carcinoma. The correct diagnosis was made on the basis of the morphologic similarities between the primary prostatic lesion and the lung lesion and was corroborated by immunohistochemical analyses.

Topics: Acid Phosphatase; Adenocarcinoma, Mucinous; Aged; Bronchial Neoplasms; Carbazoles; Carcinoembryonic Antigen; Humans; Immunohistochemistry; Male; Prostatic Neoplasms; Staining and Labeling

Serum prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP) levels were measured in 70 patients with benign prostatic hypertrophy (BPH) and in 70 patients with prostatic cancer. PSA was increased above the cutoff level of 10 ng/ml in 13% of patients with BPH and in 87% of patients with prostatic cancer. In contrast, abnormal PAP levels were found in 14 and 76% of patients, respectively. We concluded that, due to its high specificity, PSA is a useful marker in the management of patients with prostatic carcinoma and that it surpasses PAP in this regard.

Topics: Acid Phosphatase; Antigens, Neoplasm; Biomarkers, Tumor; Humans; Male; Neoplasm Staging; Prostate; Prostate-Specific Antigen; Prostatic Hyperplasia; Prostatic Neoplasms; ROC Curve

A case of epididymal metastasis from prostatic carcinoma is presented. The initial histologic findings were suggestive of adenomatoid tumor, but a diagnosis of metastatic adenocarcinoma of prostatic origin has been established by prostatic acid phosphatase and prostate-specific antigen immunoperoxidase staining.

Topics: Acid Phosphatase; Adenocarcinoma; Antigens, Neoplasm; Biomarkers, Tumor; Diagnosis, Differential; Epididymis; Humans; Immunoenzyme Techniques; Male; Middle Aged; Prostate-Specific Antigen; Prostatic Neoplasms; Teratoma; Testicular Neoplasms

The biotin-avidin immunoperoxidase assay was used to evaluate the expression of several prostate carcinoma-associated markers in formalin-fixed paraffin-embedded tissue sections of three human prostate nude mouse heterotransplant lines PC-82, PC-EW, and PC-EG. In addition to monoclonal antibodies to PSA and PAP, monoclonal antibodies to five other potentially useful markers for prostate carcinomas (TURP-27, Leu-7, 7E11-C5, PSP-19, and PD41) were tested. Tissues from two or more transplant passages were evaluated. The human prostate target antigens were found to be expressed by one or more of the three heterotransplant lines. The PC-82 and PC-EW lines were the most efficient in terms of expression of multiple prostate carcinoma-associated markers and percentage of tumor cells positive for a given prostate antigen. The staining pattern of each marker, in terms of staining intensity, number of tumor cells stained, and staining location, i.e., membrane, cytoplasmic, or ductal secretions, was similar to what has been observed in tissue sections from human prostate carcinomas. The lack of an appropriate model for evaluating the preclinical potential of these Mabs (especially TURP-27, PSP-19, and PD41) makes the findings of this study of considerable importance, and suggests that these human prostate xenografts may be useful models for exploring the diagnostic and therapeutic potential of these anti-prostate carcinoma monoclonal antibodies.

Topics: Acid Phosphatase; Animals; Antibodies, Monoclonal; Antigens, Neoplasm; Biomarkers, Tumor; Humans; Immunoenzyme Techniques; Male; Mice; Mice, Nude; Neoplasm Transplantation; Prostate-Specific Antigen; Prostatic Neoplasms; Tumor Cells, Cultured

The objective of this study was to determine if human prostate carcinoma-associated tumor markers were expressed by Dunning rat prostate carcinomas. Frozen and formalin-fixed paraffin-embedded tissues from 12 different sublines of Dunning tumors were evaluated for marker expression by immunoperoxidase staining by using a panel of 9 monoclonal antibodies, including antibodies against human PAP and PSA. None of the Dunning tumors were found to express any of the human prostate tumor markers. Both fixed and live immunofluorescent assays were performed on 5 cultured Dunning tumor cell lines, evaluated either as single cells or as monolayers. As with the Dunning tumor tissues, none of the cell cultures expressed any of the 9 human prostate tumor markers. The lack of antigen expression by the Dunning tumor tissues and cell lines suggests that these human prostate tumor markers are quite species specific. These results limit the use of the Dunning prostate tumors as models to explore the preclinical application of these human prostate carcinoma-associated monoclonal antibodies and their target antigens.

Topics: Acid Phosphatase; Adenocarcinoma; Animals; Antibodies, Monoclonal; Antigens, Neoplasm; Biomarkers, Tumor; Humans; Immunoenzyme Techniques; Male; Prostate-Specific Antigen; Prostatic Neoplasms; Tumor Cells, Cultured

Serum prostatic specific antigen (PA) and prostatic acid phosphatase (PAP) levels were measured in 113 untreated patients with prostatic cancer and in 137 patients with benign prostatic hypertrophy (BPH). Of the 113 cancer patients, 81% and 69%, respectively, were detectable by means of PA or PAP assay alone. PA was a more sensitive indicator, than PAP in all stages, especially localized disease (stages A, B and C). Using the BPH group as a negative control, specificities of PA and PAP were 81% and 94% respectively. In another group of 68 patients with BPH whose blood samples were taken immediately after prostatic manipulation, both PA and PAP levels were elevated significantly. In 87 of the 113 cancer patients the two markers were serially determined, and 22 patients presented disease progression. Concerning the sensitivity within 6 months before progression, PA appears to be more reliable than PAP in early detection of disease progression. According to Kaplan-Meier projections, the patients with normal pretreatment PA levels had significantly longer intervals to progression than did those with moderate to marked PA elevation (more than 100 ng/ml) (P less than 0.05). This study shows that PA is more reliable than PAP for detection and monitoring of prostatic cancer. Pretreatment PA levels appear to be of a high prognostic value for time to progression, irrespective of stage and treatment regimen.

Topics: Acid Phosphatase; Antigens, Neoplasm; Biomarkers, Tumor; Humans; Immunoenzyme Techniques; Male; Prognosis; Prostate-Specific Antigen; Prostatic Hyperplasia; Prostatic Neoplasms; Radioimmunoassay; Sensitivity and Specificity

Serum acid phosphatase activity, prostate specific phosphatase and prostate specific antigen were measured in 100 patients with prostatic cancer. The patients were divided according to the differentiation grade into 3 groups: G1 (well), G2 (moderately) and G3 (poorly differentiated) carcinoma. Bone metastases were identified by scintigraphy. Among the 76 M0 patients the mean levels of all 3 markers were slightly higher in patients with moderately differentiated prostatic carcinoma. Among the 24 M1 patients the primary tumour was either G2 (18 patients) or G3 (6 patients); none had G1 lesions. Significantly higher serum ACP and PAP levels were found in patients with G2 tumours than in those with G3 lesions. It was concluded that the histological differentiation grade of prostatic carcinoma did affect serum levels of prostatic tumour markers; the tendency towards higher levels in the G2 group was noticeable in both non-metastatic and metastatic cases despite the limited number of patients in the latter category. In clinical practice this information may be an important additional tool in staging prostatic cancer.

Topics: Acid Phosphatase; Aged; Aged, 80 and over; Antigens, Neoplasm; Biomarkers, Tumor; Bone Neoplasms; Humans; Male; Middle Aged; Prostate-Specific Antigen; Prostatic Neoplasms

To evaluate the usefulness of tumor markers in monitoring the patients with prostate cancer, serial measurements of serum prostate-specific antigen (PA), prostatic acid phosphatase (PAP) and gamma-seminoprotein (gamma-Sm) were performed in 78 stage C or D patients. Positive rates of each marker prior to the treatment were as follows; PA; 75%, PAP; 56% and gamma-Sm; 62% in stage C, and PA; 95%, PAP; 79% and gamma-Sm; 91% in stage D. In most cases showing PR (partial response) and S (stable) in clinical responses, these three markers decreased their serum titers corresponding to clinical course if the markers were elevated at the start of the treatment. But the usefulness of PAP was lessened because of its lower positive rate than those of PA and gamma-Sm. In 33 PD (progressive disease) cases, positive rates of each marker at time of clinical diagnosis as PD were found to be 85% in PA, 55% in PAP and 76% in gamma-Sm. And with the combination assays of these three tumor markers, positive rate was elevated to 88%. Moreover, elevation of serum values of these three markers at 3 months before the progression event were observed in 50% of PA, 39% of PAP and 46% of gamma-Sm. Then the prognostic significance of each marker was examined. In PA and PAP, there were statistical differences in non-relapsing rates between patients whose reduction rates from the pretreatment value on 7th day were more than and less than 50%. But in gamma-Sm, a statistical difference between each group was firstly observed on 14th day. As a result, in monitoring patients with prostate cancer, PA and gamma-Sm are more useful than PAP and, in prediction of patients' prognosis, PA is more useful than gamma-Sm.

Topics: Acid Phosphatase; Antigens, Neoplasm; Biomarkers, Tumor; Clinical Enzyme Tests; Follow-Up Studies; Humans; Male; Predictive Value of Tests; Prognosis; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Prostatic Secretory Proteins; Proteins; Seminal Plasma Proteins

Tumour markers viz carcinoembryonic antigen (CEA), human chorionic gonadotrophin (HCG) in 30 cases of carcinoma breast and prostatic specific acid phosphatase (PSAP) in 30 cases of carcinoma prostate were studied by peroxidase antiperoxidase technique in paraffin blocks of tissue. Twenty three (76.7%) and 20 (66.7%) cases were positive for CEA and HCG respectively. No correlation was observed between CEA and HCG status, and histological differentiation of the tumours. All the 29 cases (100%) of adenocarcinoma prostate were PSAP positive while a single case, negative for PSAP, was of transitional cell carcinoma.

Topics: Acid Phosphatase; Adenocarcinoma; Breast Neoplasms; Carcinoembryonic Antigen; Carcinoma; Carcinoma, Intraductal, Noninfiltrating; Carcinoma, Transitional Cell; Chorionic Gonadotropin; Female; Humans; Male; Prostatic Neoplasms

Between January 1972 and December 1983, 42 cases of adenocarcinoma of the prostate were admitted to Kaohsiung Medical College Hospital. The ages ranged from 46 to 90 years, with a mean of 68.6 years. The peak age group was 60-79 years of age and 2.3 per cent were less than 50 years old. The prospect for prognosis was worse if the serum acid phosphatase level was elevated. The over-all 5-year survival rate of this series was 21%. The survival rate varied according to the clinical stage: Stage A, 40%; Stage B, 31.5%; Stage D, 6.25%. On the basis of our study, the most promising approach toward increasing the survival of patients with cancer of the prostate would be earlier detection and immediate definitive treatment, including radical prostatectomy and castration. The importance of an annual physical examination, especially in men over 50 years of age which includes digital palpitation of the prostate gl, is emphasized.

Topics: Acid Phosphatase; Aged; Aged, 80 and over; Humans; Male; Middle Aged; Prostatic Neoplasms; Survival Rate; Taiwan

Serum activities of bone alkaline phosphatase (b-ALP) and of tartrate resistant acid phosphatase (tr-ACP) were evaluated in 271 cancer patients; 120 of them had bone metastases (BM) and 151 had none. Correlation coefficients, specificities, sensitivities, negative and positive predicting values were computed. They showed the important contribution that these isoenzymes can bring to the diagnosis of BM in 80 patients with prostate cancer, and to the followup of 191 patients with breast cancer. The assay results were analysed in parallel with bone scan and radiography. They were also compared to those of serum antigens: PSA and PAP for prostate cancer, and CEA and CA15.3 for breast cancer. These results clearly indicate that both isoenzymes are better correlated with BM than antigens, these antigens being markers of the whole tumor burden--primary tumor, metastases, recurrence--whereas b-ALP and tr-ACP are specific markers of bone metabolism.

Topics: Acid Phosphatase; Alkaline Phosphatase; Biomarkers, Tumor; Bone Neoplasms; Breast Neoplasms; Carcinoembryonic Antigen; Female; Humans; Male; Prostate; Prostatic Neoplasms

Carcinomas of the rat prostate induced by a single injection of N-methyl-N-nitrosourea, 7,12-dimethylbenz(a)anthracene, and 3,2'-dimethyl-4-aminobiphenyl, after sequential treatment with cyproterone acetate and testosterone propionate, were evaluated as potential animal models for prostatic cancer. All ten carcinomas examined were located in the dorsolateral prostate region and did not involve the distal parts of the seminal vesicles and coagulating glands. The incidence of urinary obstruction leading to the animals' death was 6 of 10 rats, and metastases in the lung, abdominal lymph nodes, and/or liver also occurred in 6 of 10 rats. The tumors were invasive adenocarcinomas, showing frequent perineural invasion and a variable degree of differentiation. There were ultrastructural similarities with human prostatic carcinomas, such as intracellular lumina. Plasma acid phosphatase was increased. Enzyme histochemical analysis revealed similarities with the Dunning R3327H and -HI prostatic carcinomas but was not helpful in determining the site of origin of the tumors. The gross and microscopic appearance of the tumors and the observation of preneoplastic lesions exclusively located in the dorsolateral prostate suggest this lobe as site of origin of the carcinomas. Preneoplastic lesions (n = 9) included atypical hyperplasias (n = 5) and lesions with all histological characteristics of carcinoma except for local invasion and metastases, which were classified as carcinoma in situ (n = 4). Although androgen sensitivity could not be assessed, the observed characteristics of the tumors [their long latency time (46-80 weeks), the presence of preneoplastic lesions, and the short duration of the treatment, leaving the animals intact] all indicate that the present approach is a valid animal model for the study of prostatic carcinogenesis.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Acid Phosphatase; Adenocarcinoma; Aminobiphenyl Compounds; Animals; Carcinoma in Situ; Cell Differentiation; Histocytochemistry; Hyperplasia; Male; Methylnitrosourea; Microscopy, Electron; Neoplasm Metastasis; Precancerous Conditions; Prostatic Neoplasms; Rats

The Gunma Urological Oncology Study Group has performed a multivariate statistical analysis of prognostic factors based on 353 patients with prostate cancer diagnosed between 1974 and 1984. This paper discusses the prognostic significance of erythrocyte sedimentation rate (ESR) in these patients with prostate cancer. Based on three ranges (less than 20, greater than 20- less than 50, greater than 50 mm/h) of ESR, a significant difference of survival rates among the patients was found by means of univariate analysis. ESR apparently includes components which represent anemia or infection. Hemoglobin, frequently used as a prognostic factor, was compared with ESR by means of multivariate analysis, and ESR was found to be a more useful prognostic factor than hemoglobin. Moreover ESR showed the highest partial coefficient value among the items studied (clinical stage, pathological differentiation, age, acid phosphatase, gait disturbance). It seems that ESR includes not only anemia and infection components but also provides a clue to the degree of bone metastasis or the degree of prostate cancer progression.

Topics: Acid Phosphatase; Aged; Aged, 80 and over; Blood Sedimentation; Bone Neoplasms; Gait; Hemoglobins; Humans; Male; Middle Aged; Multivariate Analysis; Predictive Value of Tests; Prognosis; Prostatic Neoplasms

The long-term effect of the luteinizing hormone-releasing hormone analogue-induced initial testosterone surge in the treatment of patients with metastatic carcinoma of the prostate still is unknown. However, acute worsening of the disease has been reported in up to 10% of the patients. To prevent such tumor flare we investigated the endocrinological effects of different types of antiandrogens administered in addition to a luteinizing hormone-releasing hormone analogue. Patients with newly diagnosed metastatic prostate cancer were pre-treated with either the steroidal antiandrogen cyproterone acetate (6) or the nonsteroidal antiandrogen flutamide (5) for 1 week before the initial injection of the depot luteinizing hormone-releasing hormone analogue Zoladex. In another 5 patients flutamide was first given 24 hours before Zoladex therapy was started. Luteinizing hormone, testosterone and prostatic acid phosphatase during month 1 of luteinizing hormone-releasing hormone analogue therapy were compared to data obtained in 5 patients treated by Zoladex alone. Only pre-treatment with cyproterone acetate was capable of preventing the Zoladex-induced testosterone surge. However, both pre-treatment regimens with either cyproterone acetate or flutamide for 1 week prevented an initial increase in prostatic acid phosphatase beyond pre-treatment levels in all patients. In contrast, in 4 of 5 patients treated with Zoladex alone and in 2 of 5 pre-treated with flutamide for 1 day an initial increase in prostatic acid phosphatase beyond the pre-treatment values was seen. Our data indicate that pre-treatment with flutamide for only 1 day may not be sufficient to prevent a luteinizing hormone-releasing hormone analogue-induced tumor flare in all cases.

Topics: Acid Phosphatase; Aged; Androgen Antagonists; Buserelin; Cyproterone; Cyproterone Acetate; Drug Therapy, Combination; Flutamide; Goserelin; Humans; Luteinizing Hormone; Male; Premedication; Prostatic Neoplasms; Testosterone; Time Factors

LNCaP cells (derived from a lymph node carcinoma of the human prostate) show androgen responsive growth. Progestagens, estradiol and antiandrogens competed with androgens for binding to the androgen receptor in the cells to a higher extent than in other androgen-sensitive systems. Optimal growth (3-4 fold increase in DNA content of 6 day cell cultures vs controls) was observed after addition of the synthetic androgen R1881 (0.1 nM). Both steroidal and non-steroidal antiandrogens did not suppress the androgen responsive growth. At a concentration of 10 nM cyproterone acetate or 100 nM RU 23908, growth was even stimulated to an extent comparable to that observed after addition of androgen. Cyproterone acetate and RU 23908 also increased the number of epidermal growth factor receptors expressed at the cell surface to a comparable level as did the androgen. Like androgens, cyproterone acetate, RU 23908 or estradiol stimulated the secretion per cell of prostate specific acid phosphatase in the culture fluid. In conclusion, antiandrogens can exert striking stimulatory effects on the proliferation of LNCaP cells probably due to a defective androgen receptor system. It is discussed that comparable changes in the specificity of the androgen receptor in prostate cancer cells may give these cells an advantage in growth rate and may contribute to development of tumors characterized as hormone independent.

Topics: Acid Phosphatase; Androgen Antagonists; Antineoplastic Agents; Cyproterone; Cyproterone Acetate; ErbB Receptors; Estradiol; Humans; Imidazoles; Imidazolidines; Male; Prostatic Neoplasms; Tumor Cells, Cultured

In previous work (P. Schulz et al., Cancer Res., 48: 2867-2870, 1988) we have demonstrated that diethylstilbestrol (DES), DES-monophosphate, and DES-diphosphate (DESDP) are generally cytotoxic at concentrations attained in patients' sera during therapeutic DESDP infusions for progressed carcinoma of the prostate. We have extended this work and addressed two questions: (a) Is DESDP itself a completely nontoxic prodrug which has to be transformed into the active species DES by a phosphatase? (b) Which metabolic or regulatory mechanism in a cell is the target of DES action? Using cell cultures in phosphatase-depleted media we could provide evidence that DESDP exerts cytotoxic activity only after conversion to DES. Oxygen electrode experiments and difference spectra with intact mitochondria demonstrated that DES did not act as an uncoupler, but inhibited electron flow from ubiquinone to cytochrome c1. Phenomena previously observed in DES-treated cells could be explained by distortion of the energy metabolism.

Topics: Acid Phosphatase; Animals; Antineoplastic Agents; Cattle; Cell Line; Cell Survival; Culture Media; Diethylstilbestrol; Electron Transport Complex III; Hot Temperature; Humans; Kinetics; Male; Mitochondria, Heart; Mitochondria, Liver; Oxygen Consumption; Prostatic Neoplasms; Rats; Tumor Cells, Cultured

The establishment of a new human prostatic cancer cell line is described. This cell line was derived from a poorly to moderately differentiated prostatic adenocarcinoma. It has been maintained in tissue culture for fourteen months and has been passed fifty-two times. This cell line has an ability to form colonies in soft agar suspension cultures, and also is transplantable to nude mice. Tumors grown in nude mice revealed a poorly differentiated adenocarcinoma with positive PSA staining. Acid phosphatase activity was detected in freeze-thawed cells by enzymatic assay. A karyotype analysis demonstrated aneuploidy with a model chromosomal number of 69 and six marker chromosomes.

Topics: Acid Phosphatase; Adenocarcinoma; Aged; Aneuploidy; Animals; Biomarkers, Tumor; Female; Humans; Immunoenzyme Techniques; Karyotyping; Male; Mice; Mice, Nude; Neoplasm Transplantation; Prostatic Neoplasms; Tumor Cells, Cultured

The predictive value of serum alkaline phosphatase (SAP) and of prostatic acid phosphatase (PAP) for response to treatment (NPCP criteria) was retrospectively assessed in patients with bone metastases from prostate cancer. Fifty-one patients had SAP measured at the start of treatment and at 1 and 2 months. In 31 of these, corresponding PAP levels were also available at each time point. SAP/PAP profiles at 2 months were classified as "increased" (increment 15% or greater), "decreased" (reduction greater than 15%) or "stable", compared with baseline levels. An additional category, SAP "flare", was also identified (SAP increment greater than 15% at 1 month, with subsequent fall at 2 months). There was a strong association between the SAP profile at 2 months and the response category, whereas the PAP profile at 2 months was more weakly associated. Using results from the 31 patients with both SAP and PAP profiles, the level of SAP was significantly better in predicting the category of response (SAP: sensitivity 94%, specificity 79%; PAP: sensitivity 53%, specificity 57%). An SAP "flare" was associated with response in 8 of 12 patients. An increase in SAP at 1 month is therefore a poor guide to progressive disease and should not be used in isolation to discontinue treatment early. The SAP profile is of value as an earlier predictor of response than X-rays or bone scans and is more reliable than the PAP profile in monitoring patients with prostate cancer and bone metastases.

Topics: Acid Phosphatase; Alkaline Phosphatase; Antineoplastic Agents; Bone Neoplasms; Clinical Enzyme Tests; Humans; Male; Predictive Value of Tests; Prostate; Prostatic Neoplasms; Retrospective Studies; Sensitivity and Specificity; Time Factors

Indices of diagnostic tests, such as sensitivity and specificity, should be determined using diagnostic test results of patients tested in clinical practice. Hospital information systems that store data on diagnostic tests and diagnoses might be used for sampling the desired study population and in the actual process of collecting the data. This paper presents, as an example, a study calculating the sensitivity and specificity of the prostate-specific acid phosphatase test. All data needed in the study were obtained from the hospital information system of Leiden University Hospital. The final health status of each patient was assessed by the cancer registry of the system. The reason for ordering the test was deduced from data on histopathological examinations of prostatic tissue. The actual selections made from the central database are described in dataflow diagrams. The sensitivity of the test was found to be 0.34 and the specificity 0.88, using a discrimination value of 1.00 U/l. The impact of the reason for ordering the test on the specificity is illustrated. Possible biases of these measured values are discussed.

Topics: Acid Phosphatase; Adult; Aged; Aged, 80 and over; Bias; Clinical Enzyme Tests; Data Interpretation, Statistical; Hospital Information Systems; Humans; Male; Middle Aged; Prostatic Neoplasms; Sensitivity and Specificity

The B1 nodule, a 1.5 cm area of induration surrounded on at least two sides by prostatic tissue of normal consistency, was defined by Jewett in 1968 as the stage of prostatic cancer best suited for treatment and cure by radical prostatectomy (RP). The area of prostatic induration suitable for RP was subsequently extended to less than one lobe (Stage B1); this extension of induration was supported by the study of Walsh and Jewett in 1980 showing a 51 percent survival free-of-disease at fifteen-year follow-up. Subsequently, clinical staging systems evolved which substaged clinical B into three categories of induration: B1N = less than 1.5 cm nodule, B1 = greater than 1.5 cm but less than one lobe, and B2 = one lobe or both lobes. To determine if digital assessment of these progressively greater degrees of induration would translate into different intervals to first progression, whether local or distant, we reviewed prostate diagrams and descriptions of all Stage B patients treated by Iodine-125 interstitial implant and external beam radiation therapy between 1974 and 1985 at our institution. Forty-six patients had B1 nodules, 78 patients B1 (less than one lobe), and 52 patients B2 (one lobe or greater). Mean follow-up was fifty-five months. We found B1N, which was also associated with well-differentiated grade and a normal acid phosphatase, to have the longest interval to progression.

Topics: Acid Phosphatase; Adenocarcinoma; Aged; Follow-Up Studies; Humans; Male; Neoplasm Staging; Probability; Prostatic Neoplasms; Retrospective Studies; Survival Rate

Between 1974 and 1983, 472 patients with clinically-staged adenocarcinoma of the prostate treated by radiotherapy had baseline and follow-up prostatic acid phosphatase (SPAP) measurements by the enzymatic Roy method. The mean pretreatment SPAP was higher in Stage C (0.65 mIU/ml) than in combined Stages A2/B (0.43 mIU/ml), (p less than 0.05). Likewise, the incidence of elevated SPAP (greater than 0.8 mIU/ml) was also higher in Stage C (12%) than in Stages A2/B (3%), (p less than 0.01). Only 3 of 113 patients in Stages A2/B had an elevated SPAP and all three remain disease-free. In Stage C elevated SPAP was an adverse prognostic factor, and patients with a normal SPAP fared worse if their value was in the upper half of normal (greater than 0.4 mIU/ml) rather than in the lower half (less than or equal to 0.4 mIU/ml). However, in Stage C, tumor grade was found to correlate with initial SPAP, so that the higher the grade, the higher was the mean SPAP and the greater was the incidence of elevated SPAP. When stratified for grade, the prognostic significance of low-normal versus high-normal SPAP in Stage C was lost. An elevated SPAP was, however, an independent adverse prognostic factor for patients with intermediate and high grade tumors. Following radiotherapy, mean SPAP values fell significantly within 1-3 months. For patients with initially normal SPAP, this fall was of no prognostic significance. In 80% of the patients with baseline elevation of SPAP, the values normalized following treatment and the relapse rate in these patients was 51%, which was still higher than the relapse rate of patients with initially normal SPAP (33%) (p less than 0.05) but was lower than the 89% relapse rate in patients whose postradiation SPAP did not normalize (p less than 0.05). Pretreatment SPAP was of independent prognostic significance for only 6% of the study population and therefore has quite limited usefulness in the management of this disease. SPAP decreases following radiotherapy, but this is of prognostic significance only for the small group of patients with elevated pretreatment values.

Topics: Acid Phosphatase; Adenocarcinoma; Adult; Aged; Biomarkers, Tumor; Humans; Male; Middle Aged; Neoplasm Staging; Prognosis; Prostate; Prostatic Neoplasms; Survival Rate

The correlation between tumor volume of untreated tumor-bearing nude mice and serum concentration of prostatic acid phosphatase (PAP/RIA) was studied in the hormone-dependent serially transplantable human prostatic tumor models PC-82 and PC-EW. The normal serum level of PAP in control male nude mice without tumor was found to be 0.9 +/- 0.3 ng/ml. Elevated PAP serum concentrations were never found in animals without tumor (a highly specific diagnostic technique). A close correlation was observed between the concentration of PAP in the serum (range 0.3 to 154 ng/ml) and the tumor volume (range 10.0 to 6,530 mm3) of 104 untreated mice bearing a PC-82 or PC-EW human prostatic tumor. This correlation was comparable in both tumor lines (p less than 0.001). The positive effect of endocrine manipulation which resulted in tumor diameter decrease or growth arrest with regressive histological patterns, showed the normal PAP serum level, too. After successful treatment PAP was found to be normal, independent from the residual tumor mass. By contrast, in the event of only retarded tumor growth, the PAP level still correlated with the tumor burden.

Topics: Acid Phosphatase; Animals; Antineoplastic Agents; Cell Line; Diethylstilbestrol; Estrogen Antagonists; Humans; Indoles; Male; Mice; Mice, Nude; Neoplasm Transplantation; Orchiectomy; Prostatic Neoplasms; Tumor Cells, Cultured

This paper evaluates the performance of several diagnostic kits for assessing levels of serum prostatic acid phosphatase on patients at different stages of cancer of the prostate. Each patient was studied with several kits. We compare results obtained for receiver operator characteristic (ROC) curve methodology with data assumed to follow a normal distribution, with log-transformed data assumed to follow a normal distribution, and when neither of these assumptions holds. There were important differences between the results of the different approaches. For these data, the normal distribution assumption should be used with extreme caution. The log-transformed based results compared favourably with the non-parametric, but unconsidered application of the method should be avoided.

Topics: Acid Phosphatase; Clinical Enzyme Tests; Data Interpretation, Statistical; Humans; Male; Normal Distribution; Prostatic Neoplasms; Reagent Kits, Diagnostic; ROC Curve

A histological evaluation of the effects of therapy has been conducted on 22 prostatic carcinoma cases, according to the criterion proposed by the committee to establish the general rule for clinical and pathological studies judging the effects of therapy in cases of prostatic cancer. Studied in particular was the relation between the histological effects of therapy and the clinical course. Marked therapeutic effects were observed in cases of low grade tumors. Further, the patients' prognosis tended to be affected by the histological grade rather than by the histological effect of the treatment. The course of the serum total acid phosphatase levels tended to correlate with the histological effect of the treatment.

Topics: Acid Phosphatase; Adenocarcinoma; Aged; Aged, 80 and over; Biomarkers, Tumor; Combined Modality Therapy; Humans; Male; Middle Aged; Prognosis; Prostatic Neoplasms; Survival Rate

Topics: Acid Phosphatase; Biomarkers, Tumor; Counterimmunoelectrophoresis; Humans; Male; Prostatic Neoplasms; Radioimmunoassay; Specimen Handling

The ability of 111In-PAY 276 (anti prostatic acid phosphatase antibody) in detecting pelvic lymph node metastasis following bipedal intra lymphatic administration was studied in five patients with carcinoma of the prostate. The labeled antibody was injected directly into the lymphatics of each foot. Planar and tomographic images radioactivity content of lymph nodes resected during staging pelvic lymphadenectomy were compared to the histologic and immunoperoxidase findings. Radioactivity in pelvic lymph nodes was prominently seen within 20 min of injection and was present 16 days later. Persistent accumulation of tracer in the lymphatics of the lower extremities was also observed in all patients 16 days post injection. Radioactivity counts in tumor-free lymph nodes were higher than in tumored lymph nodes resected. Our results demonstrate that intra lymphatic administration of 111In-labeled PAY 276 monoclonal antibody has major technical limitations, and that further research directed at the causes of tracer accumulation in the lymphatics and tumor-free lymph nodes is required.

Topics: Acid Phosphatase; Adenocarcinoma; Antibodies, Monoclonal; Antigens, Neoplasm; Humans; Indium Radioisotopes; Injections, Intralymphatic; Lymph Nodes; Male; Pelvis; Prostate; Prostatic Neoplasms; Radionuclide Imaging

In this study we examined optimization of derivatization of monoclonal antibodies and their fragments intended for use as radiopharmaceutical in radioimaging and/or radioimmunotherapy of prostatic cancer. Two different principles were used to conjugate diethylenetriaminepentaacetic acid (DTPA) to a monoclonal antibody (Mab, subclass IgG1) raised against human prostatic acid phosphatase (PAP). In addition, the F(ab')2 fragments of this Mab were also derivatized. We used the cyclic anhydride of DTPA (CA-DTPA) as a chelating agent for these two protein moieties. Furthermore, the Mab and the F(ab')2 fragments were modified site-specifically by attaching linkers, N-(p-aminobenzyl)diethylenetriaminetetraacetic acid (p-NH2-Bz-DTTA) and 1-(p-aminobenzyl)diethylenetriaminepentaacetic acid (p-NH2-Bz-DTPA), to the carbohydrate components of the parent molecules. In this study, biodistribution of the 111In-labelled derivatives was investigated in normal mice. All the derivatives of IgG1 demonstrated a slower blood clearance than the corresponding derivatives of the F(ab')2 fragments. This property was particularly pronounced in the site-specifically conjugated derivatives of IgG1. All the derivatives studied accumulated in the liver, kidney, and spleen. The CA-DTPA derivatives of F(ab')2 fragments showed the highest kidney-to-blood ratios of radioactivity compared with the other compounds studied. The derivatives of IgG1 showed a higher percentage of the injected dose in liver and spleen tissues than the derivatives of the F(ab')2 fragments. The F(ab')2 fragments studied also gave rise to site-specific derivatives, which demonstrated that carbohydrates were also present in this part of the molecule. They behaved similarly to the CA-DTPA F(ab')2 derivative in other respects, but the kidney accumulation was lower at 72 and 120 h.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acid Phosphatase; Animals; Antibodies, Monoclonal; Immunoglobulin Fab Fragments; Indium Radioisotopes; Male; Mice; Pentetic Acid; Prostatic Neoplasms; Radionuclide Imaging; Tissue Distribution

Topics: Acid Phosphatase; Adenocarcinoma; Biomarkers, Tumor; Humans; Male; Prostate; Prostatic Neoplasms

Endocrine-Paracrine cells (EP cells) in prostatic carcinomas were screened by immunohistochemical tests for neuron specific enolase, chromogranin, and serotonin and by Grimelius method. Formalin fixed, paraffin-embedded sections from 60 prostatic carcinomas were used. EP cells were detected in 16 cases (27%). The number of EP cells in hormone independent prostatic carcinomas were significantly larger than hormone dependent (p less than 0.05) and latent prostatic carcinomas (p less than 0.01). Five cases of prostatic carcinomas with abundant EP cell proliferation died of widespread metastases within 4 years, irrespective of hormone treatment. The pathologic finding was classified into the category of adenocarcinoma, partly showing carcinoid or small cell carcinoma-like features. EP cells were found in perineural invading cancer cells and also immunoreactive to both prostate specific antigen and prostate specific acid phosphatase. It is suggested that the proliferation of EP cells in prostatic carcinomas is related with the sensitivity to hormone treatment.

Topics: Acid Phosphatase; Adenocarcinoma; Aged; Aged, 80 and over; Humans; Immunohistochemistry; Male; Middle Aged; Phosphopyruvate Hydratase; Prognosis; Prostatic Neoplasms; Serotonin

Prostate-specific acid phosphatase, a secretory product of prostatic cells, may be a secondary product of the interaction of hormones with their receptor proteins. In this study we have examined two independent patient populations to see whether the intensity or extent of prostate-specific acid phosphatase and/or prostate-specific antigen staining correlated with survival and hormonal manipulation. One population of 24 patients was selected from patients undergoing surgical resection for adenocarcinoma Stage B or C at the Mayo Clinic. The second population of 123 patients was obtained from Radiation Therapy Oncology Group Protocols 75-06 and 77-06. Tissue from both populations was analyzed. In both populations, the intensity of prostate-specific acid phosphatase staining correlated with survival in a statistically significant manner. Staining with prostate-specific antigen was present in greater than 90% of specimens; data was therefore not analyzed. In those patients who subsequently relapsed and were subjected to hormonal manipulation, there appeared to be a higher likelihood of response to hormones with intense prostate-specific acid phosphatase staining.

Topics: Acid Phosphatase; Adenocarcinoma; Antigens, Neoplasm; Biomarkers, Tumor; Humans; Immunohistochemistry; Male; Prognosis; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms

Nineteen patients with newly diagnosed advanced prostatic carcinoma were treated with daily inhalations of a gonadotrophin-releasing hormone (GnRH) analogue (buserelin acetate, Hoechst 766, Frankfurt, FRG), for up to 3 years. Successful long-term suppression of luteinizing hormone (LH) and testosterone was observed without any escape of testosterone. Ten patients were considered nonresponders, whereas nine were defined as responders (had either stabilized or regressed). Serum prostate-specific markers, prostatic acid phosphatase (PAP) and prostate-specific antigen (PSA), were monitored at fixed time intervals throughout treatment in these patients. Simultaneous determinations of both markers was made under treatment in 147 samples. The results suggest a high correlation between the disease state and the level of the markers (P less than 0.0001), as well as a very high correlation between serum concentrations of the markers themselves (correlation coefficient = 0.6). Thus, the authors could not point clearly towards a superiority of any marker when monitoring response to GnRH analogue treatment. Contrary to current belief, the pretreatment values of both markers were of no prognostic value with regard to response or survival.

Topics: Acid Phosphatase; Aged; Aged, 80 and over; Antigens, Neoplasm; Biomarkers, Tumor; Buserelin; Follow-Up Studies; Hormones; Humans; Male; Middle Aged; Neoplasm Staging; Prognosis; Prostate-Specific Antigen; Prostatic Neoplasms

Prostatic carcinoma accounts for about 1% of all cancers that metastasize to the skin. The regions most frequently involved are the genital region, the head and the trunk. Clinically the lesions present as nodules; less often diffuse infiltrates, red macules and papules or tumors of an angiomatous appearance occur. Histopathological examination of skin biopsy specimens can reveal gland-like, epithelial or anaplastic differentiation of tumor cells. Prostatic origin can be proven by the immunohistological demonstration of acid prostatic phosphatase or prostatic specific antigen in paraffin-embedded specimens taken for routine histological examination.

Topics: Acid Phosphatase; Biomarkers, Tumor; Breast Neoplasms; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Prostatic Neoplasms; Skin; Skin Neoplasms

We evaluated serum prostate specific antigen before and after radical prostatectomy. In 100 consecutive patients who underwent radical prostatectomy, preoperative prostate specific antigen levels tended to increase with the increasing severity of pathological stage. However, even at levels of greater than 10 ng. per ml. the positive and negative predictive values (78 and 61 per cent, respectively) of prostate specific antigen to predict extracapsular disease were not sufficient to make this test useful alone for staging. In theory, after radical prostatectomy prostate specific antigen should be zero if no remaining prostatic tissue is present. Tests of precision and analytical sensitivity in our laboratory using a commercial prostate specific antigen assay revealed that a value of 0.4 ng. per ml. or more is different from zero at a greater than 95 per cent confidence level. With this guideline we evaluated the meaning of prostate specific antigen levels 3 to 6 months after radical prostatectomy in 59 men. Among men whose prostate specific antigen level was less than 0.4 ng. per ml. only 9 per cent demonstrated recurrence as evidenced by the development of positive bone scan or progressively elevated prostate specific antigen levels within 6 to 50 months. Alternatively, in men whose 3 to 6-month prostate specific antigen level was 0.4 ng per ml. or more there was evidence of recurrence in 100 per cent within 6 to 49 months (p less than 0.0001). Progressively elevated (more than 0.4 ng. per ml.) prostate specific antigen levels preceded recurrence from 12 to 43 months in all 6 patients who had positive bone scans, while increasing prostate specific antigen levels since radical prostatectomy have continued from 9 to 65 months in the 11 patients who have no radiological evidence of recurrent disease to date. Prostatic acid phosphatase serum values after radical prostatectomy were not useful to predict persistent disease. Prostate specific antigen values 3 to 6 months after radical prostatectomy are a sensitive indicator of persistent disease after radical prostatectomy and often precede other evidence of this occurrence by many years. This fact may alter concepts about surgical results, and possibly shorten and sharpen clinical studies involving adjuvant therapy after radical prostatectomy.

Topics: Acid Phosphatase; Adenocarcinoma; Antigens, Neoplasm; Biomarkers, Tumor; Follow-Up Studies; Humans; Male; Postoperative Period; Preoperative Care; Prostate-Specific Antigen; Prostatectomy; Prostatic Neoplasms; Radioimmunoassay; Time Factors

Serum prostate specific antigen was determined (Yang polyclonal radioimmunoassay) in 102 men before hospitalization for radical prostatectomy. Prostate specimens were subjected to detailed histological and morphometric analysis. Levels of prostate specific antigen were significantly different between patients with and without a Gleason score of 7 or greater (p less than 0.001), capsular penetration greater than 1 cm. in linear extent (p less than 0.001), seminal vesicle invasion (p less than 0.001) and pelvic lymph node metastasis (p less than 0.005). Prostate specific antigen was strongly correlated with volume of prostate cancer (r equals 0.70). Bivariate and multivariate analyses indicate that cancer volume is the primary determinant of serum prostate specific antigen levels. Prostate specific antigen was elevated 3.5 ng. per ml. for every cc of cancer, a level at least 10 times that observed for benign prostatic hyperplasia. Prostate specific antigen is useful as a preoperative marker because no patient with lymph node metastasis had serum levels of less than 10 ng. per ml. (4 times the upper limit of normal range). Of the patients with greater than 50 ng. per ml. two-thirds had microscopic lymph node metastasis and 90 per cent had seminal vesicle invasion. Serum prostatic acid phosphatase levels showed a significantly weaker correlation with cancer volume (r equals 0.51) and every other pathological parameter. Of the patients 73 per cent had serum prostatic acid phosphatase levels in the normal range (0 to 2.1 ng. per ml.), including 7 per cent who had pelvic lymph node metastasis. Postoperative prostate specific antigen values were available in 97 of 102 patients, with a mean and maximum followup of 12 and 38 months. No patient with pelvic lymph node metastasis achieved an undetectable prostate specific antigen level without adjunctive therapy (hormonal or radiation). No difference in preoperative or postoperative prostate specific antigen levels, cancer volume, seminal vesicle invasion or incidence of pelvic lymph node metastasis was seen between patients with no capsular penetration and those with minimal capsular penetration (1 cm. or less total linear extent of full thickness penetration), providing the first quantitative evidence that small amounts of capsular penetration may not be of biological or prognostic significance.

Topics: Acid Phosphatase; Adenocarcinoma; Adult; Aged; Antigens, Neoplasm; Biomarkers, Tumor; Follow-Up Studies; Humans; Male; Middle Aged; Prostate-Specific Antigen; Prostatectomy; Prostatic Neoplasms; Radioimmunoassay; Time Factors

Serum prostate specific antigen was determined (Yang polyclonal radioimmunoassay) in 183 men after radiation therapy for adenocarcinoma of the prostate. A total of 163 men had received 7,000 rad external beam radiotherapy and 20 had been implanted with 125iodine seeds. Only 11 per cent of these 183 patients had undetectable prostate specific antigen levels at a mean interval of 5 years since completion of radiotherapy. Prostate specific antigen levels after radiotherapy were directly related to initial clinical stage and Gleason score before treatment. Multiple prostate specific antigen determinations were performed with time in 124 of 183 patients. During year 1 after radiotherapy prostate specific antigen levels were decreasing in 82 per cent of the patients but only 8 per cent continued to decrease beyond year 1. Of 80 patients observed greater than 1 year after completion of radiotherapy 51 per cent had increasing values and 41 per cent had stable values. Increasing prostate specific antigen values after radiotherapy were correlated with progression to metastastic disease and residual cancer on prostate biopsy. Total serum acid phosphatase levels were poorly related to prostate specific antigen levels, were less effective in discriminating patients with metastatic disease and provided no additional information beyond that provided by prostate specific antigen.

Topics: Acid Phosphatase; Adenocarcinoma; Adult; Aged; Antigens, Neoplasm; Biomarkers, Tumor; Brachytherapy; Follow-Up Studies; Humans; Iodine Radioisotopes; Male; Middle Aged; Prostate-Specific Antigen; Prostatic Neoplasms; Radioimmunoassay; Radiotherapy, High-Energy; Time Factors

Because a change from hormone-sensitive to hormone-resistant carcinoma of the prostate often occurs concomitantly with genetic changes or as a result of the latter, the markers specific for prostatic tissues might also be affected. We therefore first studied the presence of prostatic acid phosphatase (PAP) and prostate-specific antigen (PSA) in LNCaP and LNCaP-r human prostatic carcinoma cell lines. Since both markers were found in these cell lines, we proceeded to quantitate PAP and PSA in aspiration biopsies from patients with prostate tumors. The amounts of these markers were compared with cytological findings. PAP and PSA were analyzed in the biopsy material from 120 patients using commercial radioimmunoassay (RIA) kits. DNA was determined using Riedel H33258 stain. Cytological grading was performed according to the Uropathological Study Group of Prostatic Carcinoma. Significant correlations were found between PAP/DNA or PSA/DNA values and grade of differentiation of the prostate tumor. In view of earlier reports and the results presented here, the amounts of markers or the protein pattern of tumor tissue may be a useful complement to the morphological findings and for selecting optimal therapy for patients with prostatic tumors.

Topics: Acid Phosphatase; Antigens, Neoplasm; Biomarkers, Tumor; Cell Line; DNA; Humans; Male; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms

Serum prostate-specific antigen (PSA) concentrations were measured in samples from 437 subjects, including patients with prostate cancer, patients with benign prostate hyperplasia (BPH), and patients with genitourinary cancer or benign genitourinary diseases other than prostatic, as well as patients who had undergone prostatectomy and healthy controls. PSA concentration was elevated (less than 10 ng/ml) in 84.4% of the patients with prostate cancer, in 14.1% of the patients with BPH, and in 10% of the patients with genitourinary cancer (as compared with 2% of the patients with benign genitourinary diseases). PSA concentration was not elevated in any of the patients who had undergone prostatectomy nor in the controls. In the same samples, the level of prostatic acid phosphatase (PAP) was increased (greater than 4 IU/L) in only 55.6% of the patients with prostate cancer and in 7.4% of the patients with BPH. According to these findings, the sensitivity of the test is 84.4% (55.6% for PAP) and the specificity is 92.9% (94.9% for PAP). The increase in PSA concentration in BPH correlates well with the prostate mass (gamma = 0.794), although there was no patient with a prostate weight higher than 30 gm and a PSA concentration lower than 5 ng/ml, and all patients with PSA concentrations lower than 4 ng/ml had prostate weight of less than 10 gm.

Topics: Acid Phosphatase; Adenocarcinoma; Aged; Antigens, Neoplasm; Biomarkers, Tumor; Humans; Male; Middle Aged; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms

Topics: Acid Phosphatase; Adenocarcinoma; Aged; Bone Diseases; Bone Neoplasms; Humans; Male; Middle Aged; Prostatic Hyperplasia; Prostatic Neoplasms; Radioimmunoassay

Cryosurgery is performed in poor risk cases of prostate carcinoma with dysuria. This modality has been reported to reduce the metastatic lesion postoperatively in cases of prostate carcinoma accompanied by metastasis and is employed as an adjuvant therapy of prostate carcinoma. However, many cases are already at an advanced stage and have undergone other therapeutic modalities and as a result the exact role of cryosurgery in prostate carcinoma is not clear. The present investigation was undertaken to clarify the effectiveness of cryosurgery in prostate carcinoma. The patients consisted of 21 untreated cases of histologically confirmed prostate carcinoma admitted our hospital during the 5-year period from December, 1982 to December, 1987, in all of whom treatment by cryosurgery alone was indicated, i.e., up stage B, and in whom changes in prostate carcinoma tumor markers, alkaline phosphatase (ALP), acid phosphatase (ACP), prostatic ACP detected enzymatically (PACP), and by radioimmunoassay (PAP), gamma-seminoprotein (gamma-Sm), and prostate specific antigen (PSA) were measured. During the same period, changes in tumor makers in 11 cases of prostate hypertrophy treated by transurethral resection of prostate (TUR-P) were also examined. The tumor markers were measured prior to cryosurgery and 1, 3, 7 and 14 days postoperatively as well as at 1, 3 and 6 months. Following TUR-P, in the cases of prostate hypertrophy, no postoperative changes in ALP, ACP or PACP were observed but there was elevation of PAP and gamma-Sm at day 1 and elevation of PSA until day 3, but none of these were statistically significant differences.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acid Phosphatase; Aged; Aged, 80 and over; Antigens, Neoplasm; Biomarkers, Tumor; Combined Modality Therapy; Cryosurgery; Evaluation Studies as Topic; Follow-Up Studies; Humans; Male; Middle Aged; Prostate-Specific Antigen; Prostatic Neoplasms; Prostatic Secretory Proteins; Proteins; Seminal Plasma Proteins

Serum prostatic specific antigen (PA), gamma-seminoprotein (gamma-Sm) and prostatic acid phosphatase (PAP) were evaluated in 141 patients with prostatic cancer, 121 of whom were newly diagnosed. Of the 121 untreated patients, 77, 71 and 67% were detectable by the PA, gamma-Sm and PAP markers, respectively. PA was equally or more sensitive in all stages than the other two markers. Using the benign prostatic hypertrophy group (131 patients) as a negative control, the specificities of PA, gamma-Sm and PAP were 89, 76 and 83%, respectively. Combination of PA, gamma-Sm and PAP increased sensitivity to 86%, especially in localized disease (stages A, B and C) to 74%, but did not improve specificity (67%) or efficiency (76%). During the follow-up period of 1-53 months, 24 of 141 patients with prostatic cancer had disease progression. All serial levels of gamma-Sm, PA, and PAP were positive in 17, 12 and 10 of the 24 patients within 6 months prior to detectable disease progression. gamma-Sm appeared to be more sensitive than the other two markers for early detection of disease progression. These results suggest that PA and gamma-Sm are reliable markers for detection and monitoring of prostatic cancer.

Topics: Acid Phosphatase; Antigens, Neoplasm; Biomarkers, Tumor; Humans; Male; Prostate-Specific Antigen; Prostatic Neoplasms; Prostatic Secretory Proteins; Proteins; Seminal Plasma Proteins

High-dose ketoconazole (400 mg orally three times a day) and physiologic replacement doses of glucocorticoids (hydrocortisone, 20 mg 8 AM, 10 mg 4 PM, and 8 PM) were administered to 38 patients with advanced prostatic cancer, refractory to at least initial testicular androgen deprivation. Thirty patients were completely evaluable; six were withdrawn due to possible ketoconazole-related toxicity and were considered drug failures. Two patients were unevaluable due to intercurrent therapy or inability to maintain follow-up. Ketoconazole was generally well tolerated. Mild or moderate nausea and vomiting occurred in 37% of patients, but required dose modification or discontinuation in only three patients; no hepatic damage was seen. Five of 36 patients (14%) responded to ketoconazole as determined by palpable or radiographic tumor mass reduction of 50% or greater and normalization of acid phosphatase or bone scan. Fifty percent of patients entered were stable at 90 days. Plasma androstenedione and dehydroepiandrosterone sulfate (DHEAS) were reduced markedly in almost all patients. Plasma testosterone (T) levels were low and remained unchanged, while gonadotropins were persistently elevated. Mean plasma ketoconazole content was 6.6 micrograms/mL after 28 days of therapy. While ketoconazole with hydrocortisone does suppress plasma androgens in advanced prostatic cancer patients, this infrequently causes regression of cancer that has progressed despite adequate testicular androgen ablation.

Topics: Acid Phosphatase; Aged; Aged, 80 and over; Androstenedione; Antigens, Neoplasm; Biomarkers, Tumor; Diethylstilbestrol; Drug Evaluation; Humans; Hydrocortisone; Ketoconazole; Male; Middle Aged; Orchiectomy; Pituitary Hormone-Releasing Hormones; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Testicular Hormones; Testosterone

The relative efficacy of the recently introduced gonadotropin-releasing hormone (GnRH) analogues in advanced prostatic cancer, compared with surgical castration, is still debatable. High patient compliance, lack of side effects, and absence of the psychological impact of castration, seem to be the most prominent advantages cited. Our long-term follow-up in a group of 19 prostate cancer patients treated with GnRH analogue also indicated high patient compliance and mild side effects. However, we found a discrepancy between local prostatic regression and general clinical responsiveness, and a poorer therapeutic effect than that obtained with surgical castration. In this group of patients follow-up with either prostatic acid phosphatase or prostatic specific antigen seems promising. We found a high correlation between disease state and prostatic markers. We suggest that GnRH analogues are another addition to the armamentarium for treating advanced prostatic carcinoma, yet are limited in their therapeutic effectiveness.

Topics: Acid Phosphatase; Aged; Aged, 80 and over; Antigens, Neoplasm; Biomarkers, Tumor; Buserelin; Carcinoma; Clinical Enzyme Tests; Drug Evaluation; Follow-Up Studies; Humans; Male; Middle Aged; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Time Factors

A study was performed on 290 men to compare the level of serum prostate-specific antigen (PSA) in controls, patients with benign prostatic hyperplasia (BPH) and patients with prostatic cancer. The upper limit of normal was 5.0 micrograms/l as determined in 110 elderly hospitalized males (mean age 62 years) without urological complaints. Of the 106 patients with BPH, 33% had raised values above 5.0 micrograms/l. Values above 10 micrograms/l were found in 18 BPH patients. A positive correlation was found between prostate volume (grams of tissue removed during transurethral resection) and preoperative PSA levels (r = 0.55, n = 106, p less than 0.001). PSA levels above 10 micrograms/l were found in 4% of BPH patients with a prostate volume of less than 20 g (n = 54), in contrast with 45% of patients with a prostate volume above 40 g (n = 20). The sensitivity of this PSA assay (cutoff level 10 micrograms/l) as established in 74 prostate carcinoma patients was 31% for category T0 (n = 13), 56% for category T1-2 (n = 16), 75% for category T3-4 (n = 20) and 100% for category M1 or N1-4 (n = 25). In an earlier study prostatic acid phosphatase (PAP) was measured in these same samples. PSA appeared to be much more sensitive than PAP. Seventeen of the 74 prostatic carcinoma patients (23%) had normal PAP levels but their PSA values were raised above 10 micrograms/l, while in only 2 patients an increased PAP level was combined with a normal PSA.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acid Phosphatase; Aged; Aged, 80 and over; Antigens, Neoplasm; Biomarkers, Tumor; Humans; Male; Middle Aged; Prostate-Specific Antigen; Prostatic Hyperplasia; Prostatic Neoplasms

Topics: Acid Phosphatase; Adenocarcinoma; Alkaline Phosphatase; Antigens, Neoplasm; Biomarkers, Tumor; Creatine Kinase; Humans; Male; Prostate-Specific Antigen; Prostatic Neoplasms

Prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP) serum levels were measured in 117 patients with prostatic adenocarcinoma, in 9 patients with prostatic hyperplasia and in 14 patients with other malignancies to compare the clinical usefulness of the PSA and PAP levels. PSA was elevated (PSA+) in 14 of 18 untreated patients (78%) with prostatic cancer. PAP was elevated (PAP+) only in 3 of these untreated cases (17%). Also in previously treated patients PSA was more often positive than PAP. PSA was positive in 40 of the 99 treated patients (40%), PAP was elevated only in 21 cases (21%). There was a significantly (P less than 0.001) higher tendency towards elevated PSA in the prostatic cancer patients: 32 (27%) patients with PSA+ and PAP- compared with only 2 cases (2%) with PAP+ and PSA-. The PSA+/PAP- patients were analyzed further. In seven of them the PSA level also returned to its normal level after orchiectomy or/and radiotherapy. In two patients the PSA levels indicated tumor progression earlier than PAP, their PAP levels did not rise until bone metastasizing was evident. There were also progressive disease in some patients evidenced only by increased PSA levels. In addition to cancer patients the PSA level was increased in three (30%) of the prostatic hyperplasia patients. It was also elevated in three patients with other malignancies. However, these three patients also had prostatic hyperplasia and the increase in the PSA level is considered more likely to be due to that.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acid Phosphatase; Adenocarcinoma; Antigens, Neoplasm; Biomarkers, Tumor; Humans; Male; Neoplasm Metastasis; Neoplasm Recurrence, Local; Orchiectomy; Prostate-Specific Antigen; Prostatic Hyperplasia; Prostatic Neoplasms

Both prostate specific acid phosphatase (PAP) and prostate specific anti-body (PSA) were used as the specific markers for detecting prostate cancer and its metastasis, and this was considered as the most efficient technique for detecting metastatic lesions associated with an occult carcinoma in the prostate. Altogether 44 cases were studied, including 23 cases of prostatic carcinoma, 3 cases of metastatic tumors and 18 cases of benign hypertrophy of prostate (including 4 cases with local carcinoma). Analysis of 27 cases revealed that PSA seemed more sensitive than PAP, as 17 cases of prostatic carcinoma showed positive reaction with PSA, while among them, only 3 showed negative reaction with PAP. Most of the well differentiated glandular type prostatic carcinoma showed strong positive reaction. However, the poorly differentiated solid carcinoma only showed mild positive reaction. All of the controls as well as bladder and kidney cancers showed negative reaction with either PAP or PSA.

Topics: Acid Phosphatase; Antigens, Neoplasm; Biomarkers, Tumor; Carcinoma, Intraductal, Noninfiltrating; Humans; Immunohistochemistry; Male; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms

Signet ring cell adenocarcinoma (SRCA) is an extremely rare tumor of the prostate. We document with histochemistry, immunohistochemistry, and electron microscopy an incidental "signet ring" cell adenocarcinoma of the prostate in a fifty-seven-year-old white male with chronic lymphocytic leukemia who died of an intracerebral hemorrhage. The signet ring cells stained weakly for neutral mucin and were strongly positive for both prostate-specific antigen and prostate acid phosphatase. In addition, electron microscopy demonstrated intracellular lumina with microvilli and cytoplasmic vacuoles of mucin. This case conclusively supports the existence of SRCA of the prostate.

Topics: Acid Phosphatase; Adenocarcinoma, Mucinous; Antigens, Neoplasm; Biomarkers, Tumor; Humans; Immunoenzyme Techniques; Male; Microscopy, Electron; Middle Aged; Mucins; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms

Prostate specific antigen was not detectable in 2 men with documented prostate cancer progression after radical prostatectomy. Possible explanations for prostate specific antigen remaining zero in these situations are discussed. We conclude that while monitoring prostate specific antigen is of great value in the followup of patients with prostatic cancer, it has not replaced more standard means of followup.

Topics: Acid Phosphatase; Adenocarcinoma; Aged; Antigens, Neoplasm; Bone and Bones; Follow-Up Studies; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Prostate; Prostate-Specific Antigen; Prostatectomy; Prostatic Neoplasms; Radiography

The clinical use of prostate specific antigen as a screening test for prostate cancer, as a preoperative determinant for staging of prostate cancer and to monitor response to therapy in prostatic cancer patients was evaluated in 168 men with benign prostatic hyperplasia and 231 men with prostate cancer. Only 3% of the men with benign prostatic hyperplasia had prostate specific antigen levels greater than 10 ng. per ml. compared to 44% of the men with proved prostate cancer. Preoperative prostate specific antigen levels increased with higher clinical stages of prostate cancer but there was substantial overlap among stages. Among patients with stage A1 prostate cancer who were followed expectantly none had an elevated prostate specific antigen value or metastatic disease during a followup of 15 to 120 months. After radical prostatectomy serum prostate specific antigen values decreased to undetectable levels (less than 0.6 ng. per ml.) in 89% of the patients with organ-confined disease, in 87% of those with microscopically positive margins only but in only 34% with seminal vesicles or lymph node involvement. Failure of the prostate specific antigen levels to decrease to the undetectable range after radical prostatectomy was associated with a greater likelihood of subsequent tumor recurrence. Only 3 of 18 patients (17%) treated with definitive radiation therapy had post-irradiation prostate specific antigen values of less than 0.6 ng. per ml., while in 39% the prostate specific antigens values remained greater than 4 ng. per ml. and in 4 of 18 (22%) the values were greater than 10 ng. per ml. Of patients with previously untreated stage D2 prostate cancer the mean pre-treatment prostate specific antigen value was 63.7 ng. per ml. compared to a post-hormonal therapy mean value of 31.1 ng. per ml. Of 32 patients treated with hormonal therapy 14 had stable disease, including 13 with prostate specific antigen levels of less than 10 ng. per ml. In contrast, 18 patients had progressive disease, of whom 16 had prostate specific antigen levels of more than 10 ng. per ml. We conclude that the serum prostate specific antigen assay is most useful clinically to monitor the response to therapy of prostate cancer patients.

Topics: Acid Phosphatase; Antigens, Neoplasm; Biomarkers, Tumor; Hormones; Humans; Male; Neoplasm Recurrence, Local; Neoplasm Staging; Prostate; Prostate-Specific Antigen; Prostatectomy; Prostatic Neoplasms; Radioimmunoassay

Serum concentrations of prostate-specific antigen (PSA), prostate-specific acid phosphatase (PAP), and transrectal prostatic ultrasound were utilized in the evaluation of 193 men with various urologic disorders. Of the 193 patients, 48 had prostate cancer, and the other 145 included 5 with genitourinary neoplasms, 69 with benign prostatic hypertrophy, and 71 with other non-neoplastic genitourinary disease. PSA levels were elevated in 35 patients with prostate cancer and in 25 of the 145 without prostate cancer. PAP levels were elevated in 15 with prostate cancer and in 2 of the 145 without prostate cancer. The data indicate that PSA is a more sensitive but less specific tumor marker than PAP in the detection of prostate cancer. PSA appears to be more sensitive than PAP in monitoring the response to treatment. The use of PSA and PAP jointly to detect and to monitor prostate cancer did not appear to enhance the clinical utility over that of PSA alone.

Topics: Acid Phosphatase; Adenocarcinoma; Antigens, Neoplasm; Biomarkers, Tumor; Humans; Male; Probability; Prostate-Specific Antigen; Prostatic Neoplasms; Ultrasonography

Prostate-specific antigen (PA), gamma-seminoprotein (gamma-Sm) and prostatic acid phosphatase (PAP) have been evaluated in patients with prostate cancer, benign prostatic hyperplasia (BPH), chronic prostatitis and acute prostatitis. PA has proved to be diagnostically more sensitive than PAP and gamma-Sm for the detection of prostatic cancer. Although PA may be elevated more frequently than PAP and gamma-Sm in patients with BPH, there are possibilities that these patients with elevated PA and normal PAP and gamma-Sm may have prostatic cancer or precancerous conditions not detectable in our routine diagnostic procedures. We report two cases of prostatic cancer with persistently elevated PA and diagnosed after repeated biopsies. Our data suggest that PA is a sensitive and useful tumor marker for the diagnosis of prostatic cancer. PAP and gamma-Sm in combination with PA may serve as more useful for differential diagnosis and confirmation of prostatic cancer.

Topics: Acid Phosphatase; Aged; Aged, 80 and over; Antigens, Neoplasm; Biomarkers, Tumor; Humans; Male; Prostate-Specific Antigen; Prostatic Neoplasms; Prostatic Secretory Proteins; Proteins; Seminal Plasma Proteins

A case of prostate cancer in which the parotid gland was the sole site of metastatic disease is presented. Special immunohistochemical stains of the excisional biopsy allowed for rapid, accurate diagnosis and appropriately directed successful therapy.

Topics: Acid Phosphatase; Adenocarcinoma; Aged; Antigens, Neoplasm; Biomarkers, Tumor; Humans; Immunohistochemistry; Male; Parotid Neoplasms; Prostate-Specific Antigen; Prostatic Neoplasms

Serum prostatic specific antigen (PA), gamma-seminoprotein (gamma-Sm) and prostatic acid phosphatase (PAP) levels were measured in 113 untreated patients with prostatic cancer and in 137 patients with benign prostatic hypertrophy (BPH). We used a PA-TESTWAKO enzyme immunoassay kit, gamma-Sm enzyme immunoassay kit and PAP radioimmunoassay kit. Of the 113 patients, 81.4%, 73.5% and 69%, respectively, were detectable using a single assay. PA was more sensitive than the other two markers in all stages, especially in localized disease (stages A, B and C). Using the BPH group as a negative control, specificities of PA, gamma-Sm and PAP were 85.4%, 81.0% and 94.2%, respectively. Efficiency was, respectively, 81.2%, 79.6% and 82.8%. In the follow up period, 15 patients presented disease progression. At the time of clinical detectable progression, the sensitivities of PA and gamma-Sm were both 100% (15/15), while 67% (10/15) for PAP. Concerning the sensitivity within 6 months prior to progression, gamma-Sm and PA tended to be more sensitive than PAP in early detection of disease progression. This study shows that PA is more reliable than gamma-Sm and PAP in detecting and staging of prostatic cancer. gamma-Sm and PA appear to be more reliable in earlier prediction of disease progression.

Topics: Acid Phosphatase; Adult; Antigens, Neoplasm; Biomarkers, Tumor; Blood Proteins; Humans; Male; Middle Aged; Prostate-Specific Antigen; Prostatic Hyperplasia; Prostatic Neoplasms; Prostatic Secretory Proteins; Proteins; Reagent Kits, Diagnostic; Reference Values; Seminal Plasma Proteins

The usefulness of a newly developed prostatic acid phosphatase assay based on the immunoenzymatic method (PAP-IEA) was studied. Serum samples were obtained from 22 untreated prostatic carcinoma patients, 34 benign prostatic hyperplasia patients, 32 prostatic disease-free patients and 27 normal volunteers. Mean +/- S.D. of PAP-IEA in prostatic disease-free group and normal volunteer group was 0.46 +/- 0.27 ng/ml. So, the upper limit of PAP-IEA for clinical normal range was set to 1 ng/ml (= Mean + 2S.D.). Thus, the false positive rate of benign prostatic hyperplasia was estimated at 9% and false negative rate of untreated prostatic carcinoma at 27%. Meanwhile, PAP-IEA values measured in this study were correlated well to PAP-RIA values measured in the same samples (r = 0.994).

Topics: Acid Phosphatase; Aged; Aged, 80 and over; Humans; Immunoenzyme Techniques; Male; Prostatic Hyperplasia; Prostatic Neoplasms; Reference Values

Response of prostatic cancer bone metastases to therapy (androgen withdrawal and Estracyt) was studied in 43 patients by applying scintiscanning and radioimmunodetective measurement of serum osteocalcin (OC) values. The prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP) concentrations, as sensitive probes for the overall tumor spread, were used in parallel in a monitoring procedure. A significant rise in OC levels to values elevated from a pretreatment normal level has been found in patients with a partial osseous tumor remission, and this may be easily distinguished from normal and/or subnormal OC level in bony tumor progression (P less than 0.01) and during stabilization in metastatic spread (P less than 0.01). On these bases, differences between disease progression and the "no change" response category could not be statistically recognized (P greater than 0.05). A sharp increase in circulating OC level has been recorded 1 months after the beginning of the treatment leading to bone remodeling processes and precedes improvements in scintiscan appearance. Blood OC concentration seems also to be of utility 1) in distinguishing scintigraphic flare phenomenon from a slight bone scan progression and 2) when related to scans with regions of both disease improvement and worsening. Furthermore, serum OC concentration can frequently be measured through a noninvasive procedure, thus serving as a significant addition to bone scintigraphy.

Topics: Acid Phosphatase; Aged; Antigens, Neoplasm; Bone Neoplasms; Carcinoma; Humans; Male; Middle Aged; Osteocalcin; Prognosis; Prostate-Specific Antigen; Prostatic Neoplasms; Radionuclide Imaging

The authors investigated 71 prostatic cancer patients and 45 BPH patients. The serum concentration of prostatic specific antigen (PSA), the prostatic acid phosphatase (PAP) by radio-immunoassay, the same enzyme (SPP) and the total acid phosphatase (SP) by enzymatic method were determined. In the untreated cancer patients the PSA concentration proved to be pathological in a higher proportion in all stage groups comparing to the results of the PAP, SPP, SP. The clearing of the PSA and PAP concentration on the following days and months after the beginning of the therapy reflects the excellent monitoring capability of the PSA determination. This was demonstrated by several cases too. The authors suggest more frequent use of this method in clinical practice.

Topics: Acid Phosphatase; Antigens; Biomarkers, Tumor; Epitopes; Humans; Immunoenzyme Techniques; Male; Prostate; Prostatic Hyperplasia; Prostatic Neoplasms; Radioimmunoassay

A series of 287 patients referred by their family doctors with symptoms of bladder outflow obstruction were asked to attend the hospital for "pre-clinic" screening for carcinoma of prostate (CaP). Blood samples were collected from 211 patients and analysed for serum prostate specific antigen (PSA) and prostatic acid phosphatase (PAP). Thirty-six patients had a serum PSA greater than 10 micrograms/l and 7 had PAP levels greater than 5 iu/l. In no instance was the PAP elevated without an associated increase in PSA concentration. Patients with raised markers underwent further investigations which included prostatic biopsy and/or resection; 17 patients were proved to have carcinoma of the prostate, 9 of whom had distant metastases. The specificity of PSA for detecting prostate cancer in this study was 90% with a sensitivity of 89.5%, in contrast to values for PAP of 100% and 36.8%. The routine use of PAP as a marker for prostatic cancer should be abandoned. The use of PSA as a screening test in a group of patients with prostatism appears justified, but with a positive predictive value of only 47%, its use in a mass unselected screening programme is not recommended.

Topics: Acid Phosphatase; Aged; Aged, 80 and over; Antigens, Neoplasm; Biomarkers, Tumor; Humans; Male; Middle Aged; Predictive Value of Tests; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms

The authors analyzed 150 patient files (16 controls with no prostatic pathology, 96 patients with benign prostatic hypertrophy (BPH), 38 prostate cancer patients) in an attempt to answer three questions: how should borderline values of PSA be interpreted in patients with BPH; is there a correlation between the Gleason grade and PSA levels in prostate cancer? Should both PSA and PAP concentrations be assayed? All patients underwent digital rectal examination and transrectal ultrasonography (TU), and were assayed for PSA and PAP. All prostate cancer patients had a bone scintigraphy (Bs). In view of the correlation coefficient of 0.391 (p less than 0.001), it can be affirmed that PSA and weight are linearly correlated in BPH (5 g BPH = 1 ng/ml PSA). This lower value of PSA is due to the overevaluation of prostate weight by TU. In contrast, the authors did not find any correlation between the PSA level and the Gleason grade in prostate cancer patients with a negative bone scintiscan. Finally, the sensitivity of PSA was markedly better than that of PAP (75% vs 50%), and no PSA false negative error was corrected by the PAP value.

Topics: Acid Phosphatase; Aged; Aged, 80 and over; Antigens, Neoplasm; Humans; Male; Middle Aged; Organ Size; Prostate; Prostate-Specific Antigen; Prostatic Hyperplasia; Prostatic Neoplasms; Retrospective Studies

The authors analyzed 3,079 serum determinations for prostate specific antigen (PSA) and prostatic acid phosphatase (PAP) that had been performed in 1,470 patients. The control group was comprised of 370 patients, 444 comprised the patient group with benign non-prostatic disease, 201 had malignant nonprostatic disease, 290 had benign prostatic disease (85 uncomplicated benign prostatic hypertrophy, 125 complicated benign prostatic hypertrophy, 50 acute prostatitis, 30 chronic prostatitis), 78 had untreated prostate carcinoma, and 165 were patients with prostate carcinoma under treatment. Quantification of PSA and PAP was performed by double antibody radioimmunoassay. The upper limit for normal values was set at 10 ng/ml. for PSA and 2.5 ng/ml. for PAP. Statistical analyses were performed with a personal computer using the SPSC program. Non-parametric tests were utilized throughout in the absence of a normal distribution of values for both tumor markers. In the control group, no significant differences in PSA and PAP levels were observed relative to the age group for the female patients; however, for the male patients, a significant increase was observed after age 15 for both markers. Furthermore, after age 50 PAP values became stable whereas a slight increase was observed for PSA. With regard to tumor mass, a significant correlation was found between PSA levels and the different patient groups while no remarkable differences were observed for PAP levels in those patients without or with single metastasis. We can conclude from the foregoing findings that PSA is currently the most useful tumor marker in diagnosing, staging, and monitoring prostate cancer. However, we believe that PSA and PAP are different manifestations of the prostate cell.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acid Phosphatase; Antigens, Neoplasm; Biomarkers, Tumor; Carcinoma; Female; Humans; Male; Prostate; Prostate-Specific Antigen; Prostatic Diseases; Prostatic Neoplasms

Following promising results in animal studies, Casodex (ICI 176,334) has been studied in the treatment of patients with advanced prostate cancer. At doses of 10, 30 and 50 mg, the drug was found to be well tolerated, with a moderate effect on sex hormone levels. The 50 mg dose of Casodex (daily) reduced previously elevated acid phosphatase levels by 50% or more in 71% of patients.

Topics: Acid Phosphatase; Aged; Androgen Antagonists; Anilides; Estradiol; Follicle Stimulating Hormone; Humans; Male; Middle Aged; Nitriles; Prostatic Neoplasms; Testosterone; Tosyl Compounds

For the past 6 years we used daily injection of luteinizing hormone-releasing hormone (LH-RH) agonists to treat patients with advanced prostate carcinoma. In this study we determined the hormonal response of the pituitary-testicular axis over a 2-month period and evaluated the safety and tolerance of the single intramuscular administration of sustained-release formulations of D-Trp-6-LH-RH microcapsules designed to release 50, 100, or 200 micrograms/day for over 1 month. Serum levels of LH, testosterone, and D-Trp-6-LH-RH were measured by RIA for up to 60 days in 10 patients with advanced prostatic carcinoma who had not received any previous drug therapy. After the administration of the microcapsules there was a biphasic increase in D-Trp-6-LH-RH serum levels. The maximal peak was obtained between 1 and 3 hr, and a second peak occurred between weeks 4 and 6. LH levels increased initially, with a maximal peak at 60 min, and elevated serum LH values persisted for more than 24 hr. LH levels began to fall on the second day, reaching subnormal values after 1 week. Serum testosterone rose during the first week and fell subsequently to less than 100 ng/dl. A rebound in LH and testosterone was seen about the 50th day after the microcapsule administration. Following the first week of therapy, we observed in all patients a significant decrease in bone pain, improvement in urinary flow obstruction, and a reversal of the signs of prostatism. No side effects were observed, and acceptance of the microcapsules was very good. Our results show that a single dose of D-Trp-6-LH-RH microcapsules suppresses of the pituitary-testicular axis for at least 50 days. D-Trp-6-LH-RH microcapsules facilitate the treatment and should lead to an improvement in the therapeutic response.

Topics: Acid Phosphatase; Adenocarcinoma; Aged; Antineoplastic Agents; Capsules; Delayed-Action Preparations; Drug Evaluation; Gonadotropin-Releasing Hormone; Humans; Injections, Intramuscular; Luteinizing Hormone; Male; Middle Aged; Pituitary Gland; Prostatic Neoplasms; Testis; Testosterone; Triptorelin Pamoate

A case of combined adenocarcinoma and small cell carcinoma of the prostate is described in a 58-year-old-man. Prostatic acid phosphatases and neuron specific enolase were found elevated in the serum. At autopsy the lung was free of tumor. The liver was replaced by numerous metastatic nodules and a voluminous mesenteric metastasis extended into the wall of the vessels (aorta and vena cava). Microscopic examination showed a small cell carcinoma component of the oat cell type and an adenocarcinoma component constituting 10% of the total tumor volume. By immunostaining, the small cell carcinoma component is neuron specific enolase+ and prostatic specific antigen-. The adenocarcinoma component is neuron specific enolase- and prostatic specific antigen+.

Topics: Acid Phosphatase; Adenocarcinoma; Carcinoma, Small Cell; Humans; Male; Middle Aged; Phosphopyruvate Hydratase; Prostatic Neoplasms

A murine monoclonal antibody PASE/4LJ to prostatic acid phosphatase (PAP) was used to immunostain a wide variety of sections of benign and malignant tissues (654 blocks). Non-neoplastic adult and fetal prostatic glands, primary and metastatic prostatic carcinomas, and scattered cells in prostatic and penile urethra were positive. Rat, dog and rabbit prostates were negative. Nine of 400 tumours of non-prostatic origin showed some positivity: 6/36 carcinoids, 1/9 islet cell tumours, 1/55 ovarian adenocarcinomas (serous) and one carcinosarcoma of the lung (epithelial portion). Positive staining was seen in islet cells in 4/5 specimens of normal pancreas, and in 4/9 blocks of normal pancreas surrounding a pancreatic tumour. Loops of Henle, maculae densae, and distal tubules in 10/10 fetal and 2/9 adult kidneys were also positive, with proximal tubules and collecting ducts negative. All other 159 blocks of non-neoplastic adult and fetal tissues were negative. The antibody was also affinity purified from ascitic fluid, and shown not to inhibit the enzyme activity of prostatic acid phosphatase.

Topics: Acid Phosphatase; Adult; Animals; Antibodies, Monoclonal; Dogs; Female; Humans; Immunohistochemistry; Kidney; Lung Neoplasms; Male; Ovarian Neoplasms; Prostate; Prostatic Neoplasms; Rabbits; Rats

The pretreatment bone scans on 40 patients with prostate cancer with bone involvement were reviewed and the prognostic impact of the initial extent of bone metastasis was evaluated. On the bases of the number or extent of bone metastasis, the patients were divided into 2 groups and survival for each group was compared. We also assessed the correlations between the extent on bone metastasis and other pretreatment characteristics: age, symptoms, serum acid phosphatase, serum alkaline phosphatase, and the histological differentiation of primary tumor. At the same time, the prognostic impacts of these pretreatment characteristics were evaluated. The extent of bone metastasis on the scan correlated with survival, but other characteristics did not have a predictive value except for histological grade. Though the histological differentiation of primary tumor was related to survival, the survival rates differed by the initial extent of disease among the same histological grade patients. Thus the extent of bone metastasis was shown to predict survival in metastatic prostate cancer.

Topics: Acid Phosphatase; Aged; Aged, 80 and over; Alkaline Phosphatase; Bone and Bones; Bone Neoplasms; Humans; Male; Middle Aged; Neoplasm Staging; Prognosis; Prostatic Neoplasms; Radionuclide Imaging

Topics: Acid Phosphatase; Age Factors; Female; Humans; Immunoassay; Male; Prostatic Neoplasms; Reference Values; Sex Factors

The authors have studied the prognostic interest of evaluating the prostatic acid phosphatase level before any treatment in 84 cases of stage B and C prostatic cancer. An abnormal PAP level did not significantly modify the 5-year life expectancy of patients, but was significantly correlated with a shorter period of disease-free survival. An abnormal PAP level increased the risk of recurrence; the higher the PAP level, the shorter the disease-free interval was. The disease stage (i.e., B or C) did not modify the 5-year survival period or the length of the remission. The prognosis is worse for a stage B prostatic cancer with a pathological PAP level than for a stage C cancer with a normal PAP level. A pathological PAP level seems to indicate the presence of occult metastases and should incite the clinician to actively investigate the matter.

Topics: Acid Phosphatase; Actuarial Analysis; Adenocarcinoma; Aged; Humans; Male; Prognosis; Prostate; Prostatic Neoplasms; Retrospective Studies

We analyzed 110 patients with metastatic prostate cancer (stage D2) to determine the associations between interval until progression and the pretreatment testosterone level, extent of bone metastases, performance status, race, age and pretreatment level of prostatic acid phosphatase. The median followup was 21 months (4 to 89 months). All patients received androgen deprivation therapy when metastases were identified. This multivariate analysis demonstrated that the pretreatment serum testosterone was the most significant variable (p less than 0.01) associated with interval until progression and the extent of bone metastases observed on the bone scan was the second most important variable (p less than 0.05). Age, race and prostatic acid phosphatase were not significantly correlated with the interval free of progression. Performance status was significantly correlated but it was nonsignificant in the multivariate analysis if the model already included testosterone level and extent of metastasis. Patients with a pretreatment testosterone level of less than 300 ng. per 100 ml. and more than 6 areas of increased uptake on the bone scan had the most rapid progression. We conclude that serum testosterone and extent of bone metastases are the most important of the analyzed factors in terms of interval to progression in patients with prostate cancer following androgen deprivation.

Topics: Acid Phosphatase; Aged; Aged, 80 and over; Antineoplastic Agents; Bone Neoplasms; Diethylstilbestrol; Follow-Up Studies; Gonadotropin-Releasing Hormone; Humans; Male; Middle Aged; Orchiectomy; Prognosis; Prostatic Neoplasms; Statistics as Topic; Testosterone; Time Factors

This report describes the aspiration biopsy cytology (ABC) of a case of papillary carcinoma of ductal origin, an uncommon malignant tumor of the prostate. Only one case has been previously reported in the cytology literature. Atypical papillary fragments are the distinctive cytologic findings. Similar to well-differentiated acinar carcinoma of the prostate, the cytologic features of malignancy in this lesion may be subtle, and diagnosis is based on the presence of the cytologic pattern. Positive immunohistochemical staining with prostate-specific acid phosphatase confirms the prostatic origin. Application is made of quantitative DNA analysis for prognostic determination.

Topics: Acid Phosphatase; Aged; Biopsy, Needle; Carcinoma, Papillary; DNA, Neoplasm; Humans; Immunoenzyme Techniques; Male; Prognosis; Prostatic Neoplasms

Thirty three cases of prostatic adenocarcinoma treated by total perineal prostatectomy were studied clinicopathologically and immunohistochemically. There were 17 patients with clinical stage B, 12 with stage C and 8 with stage D. Interrelationship of tumor grade, surgical local tumor extent, vessel invasion, perineural invasion and bone metastasis was examined. For the identification of the vessel invasion, Ulex europaeus agglutinin 1 was adopted immunohistochemically. Tumor grade and local tumor extent were respectively correlated with bone metastasis. Vessel invasion was correlated with local tumor extent. Eight of 18 cases (44%) with vessel invasion and none of 15 cases without vessel invasion had bone metastasis. Although correlated with grade, perineural invasion had no significant effect on bone metastasis. The investigation of tumor staining used by monoclonal antibody for prostatic acid phosphatase (PSAP) disclosed that negative stained cases were associated with lower grade tumors and that one of 14 positive stained cases (7%) and 7 of 19 negative stained cases (36%) had bone metastasis. We concluded that vessel invasion may be a new prognostic pathological parameter and that monoclonal PSAP staining is also a useful method to predict malignant potential of prostatic cancer.

Topics: Acid Phosphatase; Adenocarcinoma; Aged; Aged, 80 and over; Blood Vessels; Bone Neoplasms; Humans; Immunoenzyme Techniques; Male; Middle Aged; Neoplasm Invasiveness; Prognosis; Prostatectomy; Prostatic Neoplasms

We compared the values obtained by double-antibody radioimmunoassay (RIA) and immunoenzyme assay (IEA) for measuring the prostatic acid phosphatase (PAP) in human serum. Mean PAP value of IEA in normal persons was 0.582 +/- 0.228 ng/ml (M+2SD, 1.038 ng/ml). Correction of two methods in benign prostatic hypertrophy (BPH) and prostate cancer patients was excellent [r = 0.9504, Y (IEA) = -0.4378 + 0.6529X (RIA)]. False positive cases were two by IEA and one by RIA in BPH patients.

Topics: Acid Phosphatase; Adult; Aged; Aged, 80 and over; Humans; Immunoenzyme Techniques; Male; Middle Aged; Prostatic Neoplasms; Reagent Kits, Diagnostic

Prostatic carcinoma is the second leading cause of cancer mortality in American men. Twenty-seven thousand deaths from this aggressive neoplasm were predicted for 1987. Although this malignancy has metastasized to almost all of the structures in the head and neck, it demonstrates a pathophysiologic proclivity for the supraclavicular lymph nodes. Combining fine-needle aspiration with immunohistochemical techniques produces a cost-effective method to expedite the diagnosis of this hormone-responsive tumor. Four patients presenting with prostatic carcinoma and neck metastasis in a three-year period are reported and discussed.

Topics: Acid Phosphatase; Aged; Head and Neck Neoplasms; Humans; Lymphatic Metastasis; Male; Middle Aged; Prostatic Neoplasms

The therapeutic indications in prostatic cancer depend on the regional and distant extension of the cancer and are difficult to assess before lymphadenectomy. Radioimmunodetection of lymph node involvement with monoclonal anti-prostatic acid phosphatase (PAP) antibodies can be proposed as a noninvasive alternative to lymphadenectomy. Fifteen patients with various stages of histologically proven prostatic cancer were examined by immunolymphoscintigraphy (ILS) before treatment to detect lymph node metastases. These patients had Stage A (n = 7), Stage B (n = 3), Stage C (n = 2), and Stage D (n = 3) tumors. They received between 100 and 400 micrograms of monoclonal antibody 227 A in the form of F(ab')2 fragments labeled with iodine 123 (123I). The antibody was injected directly into the periprostatic area. ILS images were obtained after 1, 3, 6, and 24 hours. Three days later, each patient underwent a lymphadenectomy for histologic examination. The results of the histologic examination and ILS were compared. In ten patients, the examination did not show any images capable of being interpreted as lymphadenopathy and histologic examination confirmed the integrity of the nodes examined. In five cases, scintigraphy suggested the presence of lymph node invasion by prostatic cancer and this was confirmed by histologic examination in three of the five cases. Overall, in terms of lymphadenopathy, this examination had a sensitivity of 100% and a specificity of 83%. Therefore, ILS appears to be capable of detecting lymph node metastases in prostatic cancer.

Topics: Acid Phosphatase; Aged; Antibodies, Monoclonal; Bone Neoplasms; Humans; Immunoglobulin Fab Fragments; Iodine Radioisotopes; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Staging; Predictive Value of Tests; Prostate; Prostatic Neoplasms; Radionuclide Imaging

One hundred ten patients with metastatic prostate cancer (Stage D2) were analyzed to determine the associations among time until progression and the pretreatment testosterone level, extent of bone metastases as indicated by a semiquantitative grading scale for extent of disease, performance status, race, age, and the pretreatment level of prostatic acid phosphatase (PAP). The median follow-up period was twenty-one months, with a range of four to eighty-nine months. All patients received androgen deprivation at the time metastases were identified. A multivariate analysis demonstrated that pretreatment serum testosterone was the most significant variable associated with time until progression (P less than 0.01) and that the extent of bone metastases observed on the bone scan was the second most important variable (P less than 0.05). The following factors did not significantly correlate with progression-free intervals: age, race, and PAP. The performance status was significantly correlated, but was nonsignificant in the multivariate analysis when the model already included the testosterone level and the extent of bone metastases. Patients with a pretreatment testosterone level of less than 300 ng/dL and with more than six areas of increased uptake on the bone scan progressed more rapidly.

Topics: Acid Phosphatase; Adenocarcinoma; Aged; Aged, 80 and over; Bone Neoplasms; Follow-Up Studies; Humans; Male; Middle Aged; Prognosis; Prostatic Neoplasms; Statistics as Topic; Testosterone; Time Factors

We have studied embryonic and fetal differentiation of the human prostate in relation to androgen-producing Leydig cell differentiation. We have studied the differentiation of human prostatic glands and the synthesis of acid phosphatase in vivo and in vitro. These studies have shown that the mesenchyme at the level of the openings of the para- and mesonephric ducts to the urethra was the local initiator of prostatic differentiation. All prostatic acini developed by epithelial outgrowths from the urethral epithelium. None of them grew from para- or mesonephric ducts. However, the epithelium on the colliculus seminalis differed from the rest of the urethral epithelium morphologically and in acid phosphatase content. Androgens accelerated differentiation in vitro and acid phosphatase activity was shown to be present in prostatic urethral epithelium and prostatic acini both in vivo and in vitro. According to these studies embryonic differentiation gives no direct answer to the localisation of adult neoplastic changes in different parts of the prostate, although in the posterior part there might be a mixture of cells from ductal and urethral epithelium. Secretion of acid phosphatase seems to be a constitutional phenomenon of this part of epithelium and is partly regulated by androgens. Epitheliomesenchymal interaction is important in differentiation and the role of this interaction in adult diseases might be valuable to be studied.

Topics: Acid Phosphatase; Androgens; Cell Differentiation; Humans; Leydig Cells; Male; Prostate; Prostatic Neoplasms

Sixty seven cases of stage D prostatic carcinoma were analyzed according to age, chief complaints, histopathological types, metastatic sites, and serum acid and alkaline phosphatase levels. In spite of metastasis, which were in 62 cases (92.5%) to bone, in 17 cases (25.4%) to lymph nodes, and in 3 cases (4.5%) to the lung, the most common chief complaints were symptoms related to the primary lesion, such as dysuria and urinary frequency. There was no significant correlation between the incidence of bone metastasis and histopathological type. However, higher incidence of lymph node metastasis was observed in the histological types of moderate and poorly differentiated adenocarcinoma than well differentiated type. When cases were divided into two groups by age, significant differences were observed between younger (64 less than or equal to years old) and older (greater than or equal to 65 years old) groups in the following points: 1) Histopathologically, well differentiated type was not recognized in the younger group, while three histological types of well, moderate and poorly differentiated adenocarcinoma, were equally distributed among the older one. 2) Although there was no significant difference in the incidence or the numbers of metastatic sites to bone between the two groups, the younger patients had less symptoms related to bone metastasis. The prominent symptoms in the younger group were complaints about voiding.

Topics: Acid Phosphatase; Adenocarcinoma; Aged; Aged, 80 and over; Aging; Alkaline Phosphatase; Bone Neoplasms; Humans; Lymphatic Metastasis; Male; Middle Aged; Prostatic Neoplasms

In developing diagnostic reagents for the radioimaging of prostatic cancer, methods were optimized for the purification of two mouse IgG1 monoclonal antibodies raised against prostate-specific acid phosphatase and produced in cell culture. Two different two-step methods were selected. One method consisted of two successive ion exchange chromatographic steps on Mono S and Mono Q; in the other method, Mono S chromatography was followed by hydrophobic interaction (Alkyl Superose) chromatography. In both cases, fast protein liquid chromatography (FPLC) instrumentation was used. The antibodies were purified from cell culture media containing fetal calf serum (1-5%). Highly pure (greater than 95%) IgG1 antibodies, free of contaminating serum-derived proteins or column materials, were obtained in good yield (greater than 90% recovery). The purified antibodies completely retained their immunological reactivity towards prostate-specific acid phosphatase and were sterile and pyrogen-free. Since the monoclonal antibodies produced were intended for applications in vivo, an essential feature of the methods selected was the availability of in situ cleaning procedures for sterilization of the gel materials and for the inactivation of viruses and pyrogens in the gels. The methods developed could be readily scaled up for preparative purposes.

Topics: Acid Phosphatase; Acrylic Resins; Animals; Antibodies, Monoclonal; Biomarkers, Tumor; Chromatography, Gel; Chromatography, Ion Exchange; Humans; Immunoglobulin G; Male; Mice; Prostate; Prostatic Neoplasms; Radionuclide Imaging

Expression of the p21 protein of the ras oncogene family was studied in a case of human prostatic adenocarcinoma tissue and the cell line was derived from the primary tumor. Flow cytometry analysis of the tumor cells obtained from the primary tumor indicated that approximately 25 per cent of the cells were positive for this oncogene product. However, by the immunoperoxidase method almost all of the tumor cells at the vertebral metastatic sites in the same patient were positive for the p21 protein. The cell line established from the primary tumor displayed 2 distinct subpopulation growth patterns in vitro: a monolayer, density-inhibited growth and a multicellular aggregate type growth morphology. These 2 subpopulations could be separated by density elutriation centrifugation. The isolated subpopulation cells were noted to express prostatic acid phosphatase and prostate specific antigen at high frequency. High levels of expression of these 2 prostatic markers also were found in the tumor cells at the vertebral metastatic sites. However, when the isolated subpopulations were analyzed for the expression of p21 protein, the multicellular grown cells were almost 90 per cent positive for the p21 antigen, whereas only approximately 5 per cent of the monolayer grown cells were positive for the same protein. Our findings suggest that primary prostatic carcinomas are composed of heterogeneous subpopulations of neoplastic cells while only specific subpopulations have metastatic potential. Quantification of prostatic acid phosphatase and prostate specific antigen in the primary tumor cells probably will not offer a predictive value for the eventual behavior of the tumors. However, evaluation of oncogene products, such as the p21 protein, may be useful as a clinical predictor for metastatic potential.

Topics: Acid Phosphatase; Adenocarcinoma; Antigens, Neoplasm; Biomarkers, Tumor; Bone Neoplasms; Cell Line; Flow Cytometry; Fluorescent Antibody Technique; Humans; Male; Oncogene Protein p21(ras); Oncogene Proteins, Viral; Prostate-Specific Antigen; Prostatic Neoplasms

We have studied the clinical utility of a recently developed assay for a prostate specific protein (prostate-specific antigen). Histochemical demonstration of prostate-specific antigen has a higher sensitivity and specificity for the diagnosis of prostate carcinoma than does prostatic acid phosphatase. Similarly, measurement of prostate-specific antigen by immunoassay in serum is a more sensitive indicator of tumor stage and recurrence after therapy than prostatic acid phosphatase. More information is needed, however, regarding the variation in this protein with different therapeutic methods.

Topics: Acid Phosphatase; Antigens, Neoplasm; Biomarkers, Tumor; Humans; Immunohistochemistry; Male; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Radioimmunoassay

Changes in the serial measurements of serum prostatic acid phosphatase (PAP), and prostatic specific antigen (PSA) have been compared against changes in serial bone scans in 120 patients with prostatic cancer. Of 54 patients who presented with negative bone scans 10 developed skeletal metastases, the PAP and PSA levels were rising in 5 and 9 of these patients, respectively. Local progression occurred in a further 9 patients in whom PAP was rising in 8 and PSA in all 9. In the 66 patients with previously documented skeletal metastases bone scan evidence of progression was seen in 36. At the time of the first evidence of progression PAP was rising in 20 (55%) and PSA was rising in 26 (72%). In 4 patients neither marker was raised at the time of first evidence of progression. We discuss the value of 'routine' serial bone scintigraphy in monitoring patients with prostatic cancer.

Topics: Acid Phosphatase; Aged; Aged, 80 and over; Antigens, Neoplasm; Biomarkers, Tumor; Bone and Bones; Bone Neoplasms; Humans; Male; Middle Aged; Prostate-Specific Antigen; Prostatic Neoplasms; Radionuclide Imaging

We used a mixture of antisera to prostatic specific acid phosphatase, prostatic specific antigen, epithelial membrane antigen and cytokeratin to examine multiple marrow aspirates from patients with local (15) and metastatic prostatic carcinoma (15), and benign prostatic hypertrophy (10). We found moderate to large numbers of tumor cells in the bone marrow of 11 of 15 (73 per cent) patients with known metastatic disease and small numbers of abnormal cells in 2 of 15 (13 per cent) patients with apparently local disease. No tumor cells were found in patients with benign prostatic hypertrophy, and only 2 patients with metastatic disease had tumor cells in the bone marrow when conventional hematomorphological preparations were examined. These findings suggest that immunocytochemistry can increase the detection rate of metastatic prostatic carcinoma cells. Further followup of larger numbers of patients with local carcinoma will reveal whether the presence of micrometastases denotes a poor prognosis.

Topics: Acid Phosphatase; Aged; Aged, 80 and over; Antigens, Neoplasm; Biomarkers, Tumor; Bone Marrow; Humans; Immunohistochemistry; Keratins; Male; Membrane Glycoproteins; Middle Aged; Mucin-1; Neoplasm Metastasis; Prostate-Specific Antigen; Prostatic Hyperplasia; Prostatic Neoplasms

Spontaneous circadian variations of prostate specific antigen (PSA) and prostatic acid phosphatase (PAP), determined simultaneously by radioimmunoassay (RIA), were investigated by multiple sampling, over a 24-hour period, in 32 patients with prostatic cancer. In 29/32 patients (91%), the coefficient of variation of 24-hour values, for either marker, was greater than that of the RIA method at the same range of values; stage D patients showed the greatest spontaneous variability. Fluctuations around the mean of 24-hour values ranged from -65% to +85% for PAP, from -72% to +190% for PSA, occurring random and independently for each marker. Variability was about 20% greater for PSA than for PAP. The existence of spontaneous fluctuations should be considered in multiple marker evaluation of prostatic cancer patients.

Topics: Acid Phosphatase; Adenocarcinoma; Aged; Antigens, Neoplasm; Biomarkers, Tumor; Circadian Rhythm; Humans; Male; Middle Aged; Prostate-Specific Antigen; Prostatic Neoplasms; Radioimmunoassay

Prostatic acid phosphate (PAP), prostate-specific antigen (PSA), and beta-microseminoprotein (beta-MSP) were regularly localized immunohistochemically to the epithelium of the acini and that of the ducts in the nodules of 24 cases of benign prostatic hyperplasia. The immunohistochemical distribution of these three prostatic-secreted proteins was also examined, with monoclonal antisera against PAP and PSA and with polyclonal antisera against PAP, PSA, and beta-MSP, in a series of 40 cases of prostatic adenocarcinomas graded according to the WHO classification. Highly differentiated (grade I) carcinomas showed a high incidence of PAP-, PSA-, and beta-MSP-immunoreactive cells. As in the normal and hyperplastic prostate parenchyma, highly differentiated (grade I) carcinomas were found to contain an almost equal number of PAP-, PSA-, and beta-MSP-immunoreactive cells. When semiquantitatively assessed, the incidence of PAP-, PSA-, and beta-MSP-immunoreactive cells was found to be lower in the moderately and poorly differentiated (grades II and III) tumors than in the highly differentiated ones; they also showed greater staining variability. Tumor cells immunoreactive with a monoclonal antiserum raised against PAP in carcinomas of grades II and III were less frequent than tumor cells immunoreactive with antisera against PSA, beta-MSP, and a polyclonal antiserum against PAP. The almost identical distribution of PSA and beta-MSP in carcinomas of grades II and III suggests that PSA and beta-MSP are not less sensitive tumor markers than PAP for the monitoring of the course and the treatment of prostatic carcinomas.

Topics: Acid Phosphatase; Adenocarcinoma; Aged; Aged, 80 and over; Biomarkers, Tumor; Epithelium; Humans; Immunoenzyme Techniques; Immunohistochemistry; Male; Middle Aged; Prostate; Prostatic Hyperplasia; Prostatic Neoplasms; Prostatic Secretory Proteins; Proteins; Seminal Plasma Proteins

In 261 non-selected patients (190 prostate adenoma, 71 carcinoma of prostate) prostatic acid phosphatase (PAP) was measured prior to treatment using three different commercial enzyme immuno assays. According to the normal values given by the manufacturers we found different specificities (ranging from 0.61-0.88) and sensitivities (0.45-0.75). However, the receiver-operating-characteristics-curves (ROC) for each of the tests were similar. Since we observed a considerable overlapping of PAP-activity measured in patients with prostatic adenoma and carcinoma we tried to optimize the specificity of the three assays. The actual cut-off value was determined by use of a tangent with the "a posteriori prevalence" (adenoma:carcinoma = 190:71 = 2.6) on each ROC-curve. With this method we found a similar range of sensitivity (0.38-0.48) and specificity (0.96-0.97). The use of a cut-off-value according to the "a posteriori prevalence" results in optimizing of sensitivity and specificity by taking into account the specific long term distribution of prostate adenoma/carcinoma in the respective material.

Topics: Acid Phosphatase; Diagnosis, Differential; Humans; Immunoenzyme Techniques; Male; Prostatic Hyperplasia; Prostatic Neoplasms

Immunohistochemical techniques using antibodies to prostate specific antigen (PSA) and prostate specific acid phosphatase (PAP) have greatly increased the feasibility of reliable diagnosis of primary or metastatic prostatic carcinoma. A review of the literature showed the diagnostic specificity of antibodies to PSA or PAP to be 100% and 87-100%, respectively. The corresponding figures for diagnostic sensitivity were 94-100% and 90-100%.

Topics: Acid Phosphatase; Adenocarcinoma; Antigens, Neoplasm; Biomarkers, Tumor; Humans; Immunohistochemistry; Male; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms

Primary signet-ring-cell carcinoma of the prostate is extremely rare. We report eight patients with prostatic adenocarcinomas containing significant numbers of signet-ring cells, one of whom presented initially with supraclavicular lymph node metastasis. Patient ages ranged from 50 to 80 years (mean, 67.5). None of the patients had received any form of therapy before biopsy or surgery. All patients presented with advanced disease (five with stage C and three with stage D). All tumors were poorly differentiated adenocarcinomas, M.D. Anderson Hospital system grade IV, Gleason's combined score of 9 or 10. The signet-ring cells were negative for neutral and acid mucins but immunoreactive for prostatic-specific antigen and prostatic acid phosphatase. Ultrastructurally, the signet-ring-cell appearance resulted either from the presence of intracytoplasmic lumina or from vacuoles. Signet-ring cells were also present at the metastatic sites. We conclude that (a) signet-ring-cell carcinoma of the prostate is a variant of poorly differentiated adenocarcinoma of the prostate; and (b) when a metastatic signet-ring-cell carcinoma with negative intracytoplasmic mucin is identified, a prostatic origin should be considered, and prostatic-specific antigen and prostatic acid phosphatase immunostaining should be performed.

Topics: Acid Phosphatase; Adenocarcinoma, Mucinous; Aged; Antigens, Neoplasm; Biomarkers, Tumor; Humans; Immunoenzyme Techniques; Lymph Nodes; Male; Microscopy, Electron; Middle Aged; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms

Serum prostatic-specific antigen (PSA) and prostatic acid phosphatase (PAP) were determined simultaneously in 241 patients presented to the Urology Department. The patients consisted of 140 prostatic carcinoma patients (34 newly diagnosed and 106 previously treated) and 101 patients with benign prostatic hypertrophy (BPH). Prostatic acid phosphatase was measured by two different methods, an enzymatic method (PAP-EA, Boehringer) with tartrate inhibition and an immunoenzymetric assay (PAP-IEMA, Hybritech). The concentration of prostatic specific antigen in serum was measured using a recently introduced immunoradiometric assay (PSA-IRMA, Hybritech). Receiver operating characteristic curves were constructed to compare the diagnostic value of the different tests at different cutoff values. The diagnostic efficiencies of the PAP-EA and the PAP-IEMA appeared to be similar. A better diagnostic efficiency for PSA compared to PAP was found independent of the cutoff value. The upper-normal limit of 2.7 micrograms/l for PSA, as suggested by the manufacturer and mentioned in the literature introduces too many false-positive results. We therefore selected 10 micrograms/l as the upper-normal limit for PSA (sensitivity 57%, specificity 88%). Combined sensitivity found for PAP + PSA was 37% with a specificity of 97%. A literature survey is included to allow better comparison with data published elsewhere.

Topics: Acid Phosphatase; Antigens, Neoplasm; Biomarkers, Tumor; Humans; Immunoenzyme Techniques; Male; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms

Concurrent measurements of serum TPA and PAP concentrations by double antibody radioimmunoassays were done in 49 patients with prostatic cancer in different clinical stages. The reference group comprised patients suffering from BPH. Positive TPA was found in 32.7% of cancer patients, the lowest percentage in stage A (11.1%) and the highest in stage D (55.6%). The additional value as a diagnostic aid of the TPA test was revealed on the basis of examination of the selected group of patients with not increased PAP. Positive TPA was found in 16.7% of patients: none in stage A, 22.2% in stage B, and 33.3% in stage D. Prostatic cancer remains the most common malignancy of the genitourinary tract. The improvement in the results of treatment involves not only a modernization of treatment modalities but also the introduction of laboratory tests which give the most ample information on the stage of tumour development and improve possibilities to control tumour therapy. Besides the refinement of the determination procedures of specific prostatic markers, prostatic acid phosphatase (PAP), through radio- and enzyme-immunological methods, there is a search for additional markers which might be helpful in diagnosis and follow-up of treatment.

Topics: Acid Phosphatase; Aged; Antigens, Neoplasm; Carcinoma; Humans; Male; Middle Aged; Peptides; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Tissue Polypeptide Antigen

Epithelial cell differentiation was evaluated in 15 samples of duct-acinar dysplasia, a putative premalignant lesion of the prostate, through immunohistochemical staining for five differentiation markers. Prostate-specific antigen (PSA), prostatic acid phosphatase (PAP), Leu-7, pepsinogen II (PG II), and tissue plasminogen activator (t-PA) are all constituents of seminal fluid that are produced by prostatic epithelium. Dysplasia foci were classified into three grades of severity and their locations mapped by camera lucida drawings of each slide. The degree of abnormal staining with each antibody was recorded on the map, and its correlation with dysplasia grade was evaluated. PSA, PAP, and Leu-7 staining were reduced in dysplasia and often absent in severe dysplasia, indicating that reduced differentiation is an early change in prostatic carcinogenesis. PG II and t-PA stains were sometimes positive in a region where they are usually absent, suggesting that deregulation of differentiation markers may accompany reduction in differentiation in these preneoplastic lesions.

Topics: Acid Phosphatase; Antibodies; Antigens, Differentiation; Antigens, Neoplasm; Cell Differentiation; Humans; Immunochemistry; Male; Pepsinogens; Precancerous Conditions; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Tissue Plasminogen Activator

Topics: Acid Phosphatase; Adenocarcinoma; Antigens, Neoplasm; Humans; Male; Prostate-Specific Antigen; Prostatic Neoplasms

Recognition of disseminated adenocarcinomas potentially responsive to current treatment programs is an important objective in the management of cancer patients. Metastatic adenocarcinoma of the prostate gland is a malignant entity which often can be palliated effectively by hormonally based therapeutic strategies. In cases of metastatic prostate cancer presenting with typical clinical features, the correct diagnosis can be readily achieved, but in patients with less obvious presentations the diagnosis of prostatic carcinoma may be overlooked. In the current report, a group of elderly men presenting with a clinical syndrome resembling either metastatic primary adenocarcinoma of the lung or primary adenocarcinoma of the lung coexisting with prostate cancer were found in fact to have metastatic prostatic carcinoma as their sole disease process. In each case, cytologic characterization of clinically involved tissue specimens by the prostate specific antigen and prostatic acid phosphatase immunohistochemical markers enabled clinical investigators to arrive at the correct diagnosis. Other clinical features, such as a positive bone scan and an enlarged prostate gland on physical exam and/or radiographic studies were noted to be present in these patients. All the patients in the current series responded to hormonal treatment regimens once the diagnosis of metastatic prostate cancer had been established. In elderly male patients presenting with what appears to be primary adenocarcinoma of the lung, the diagnosis of metastatic prostate cancer should be considered and when necessary evaluated by the use of appropriate clinical and immunohistochemical studies.

Topics: Acid Phosphatase; Adenocarcinoma; Aged; Antigens, Neoplasm; Biomarkers, Tumor; Diagnosis, Differential; Humans; Immunohistochemistry; Lung Neoplasms; Lymph Nodes; Male; Neoplasms, Unknown Primary; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms

The serum prostate specific antigen (PA) was determined with the Diagnostic Products Cooperation (DPC) PSA double antibody radioimmunoassay kit. The upper limit of the normal range was set at 4 ng/ml which was the mean + 3S.D. for males over 50 years old in a mass examination. For comparison, prostatic acid phosphatase (PAP), and gamma-seminoprotein (gamma-Sm) were determined using an Eiken kit and Chugai kit, and PA was also assayed using another kit (Eiken, Travenol). Positive rate of PA and PAP in the untreated prostatic cancer was 75 and 33% in Stage A, 100 and 0% in Stage B, 100 and 100% in Stage C, 100 and 67% in Stage D1, 100 and 80% in Stage D2 and 73 and 33% in benign prostatic hypertrophy (BPH), respectively. The level of PA determined during the follow-up of prostatic cancer showed the usefulness of simultaneous PA and PAP assays for monitoring the clinical course. The PA level using a DPC kit was highly correlated to that of PA using other kit, but the correlation with gamma-Sm and PAP was low. These results show that the DPC kit is useful for determining PA, and determination of PA and PAP is of great value both in diagnosis and in the follow-up of prostatic cancer, but the high positive rate in BPH remains a problem.

Topics: Acid Phosphatase; Aged; Aged, 80 and over; Antigens, Neoplasm; Biomarkers, Tumor; Humans; Male; Middle Aged; Prostate-Specific Antigen; Prostatic Hyperplasia; Prostatic Neoplasms; Prostatic Secretory Proteins; Proteins; Reagent Kits, Diagnostic; Seminal Plasma Proteins

Development of serum assays for prostate-specific antigen (PSA) has provided physicians with a new marker for carcinoma of the prostate. PSA was compared to prostate acid phosphatases (PAP), the reference serum marker, in 162 patients including 54 patients with carcinoma of the prostate (CP), 84 patients with benign hypertrophy of the prostate (BHP), and 24 controls free of prostate disorders. PSA appeared more sensitive but less specific than PAP. Results showed that PSA is not suitable for routine screening in the population at large where BHP is common. In BPH, the rise in PSA concentrations parallels the size of the hypertrophy. However, in patients with CP, PSA seems more sensitive than PAP for evaluating tumor spread and response to treatment. The prognostic bearing of increased levels in patients with apparently localized carcinomas remains to be elucidated.

Topics: Acid Phosphatase; Aged; Aged, 80 and over; Antigens, Neoplasm; Biomarkers, Tumor; Diagnosis, Differential; Humans; Male; Middle Aged; Prognosis; Prostate-Specific Antigen; Prostatic Hyperplasia; Prostatic Neoplasms

Prostate-specific antigen (PSA) and prostate acid phosphatase (PAP) were assayed using a radioimmunologic method in 306 patients from November 1986 through April 1987. Study patients included 10 women, 10 men under forty years of age, 25 patients with malignancies involving structures other than the prostate, and 280 patients with diseases of the prostate ie. benign hypertrophy of the prostate (BHP) (n = 170), or histologically-proved carcinoma of the prostate (CaP) (n = 110). Serum PSA levels were undetectable in women and following total prostatectomy; levels of 3 ng/ml were found in young men, with no circadian variations. Non-prostatic carcinomas had no influence on PSA levels. PSA levels in BHP patients were 6.9 +/- 8.4 ng/ml and correlated positively with the weight of the gland. In patients with carcinoma of the prostate, PSA levels were 24.4 +/- 19.3 ng/ml, correlated positively with tumor spread, and returned to normal following successful palliative hormone treatment, with new increases reflecting recurrences. PSA assays are of little value for screening for carcinoma of the prostate; however carcinoma of the prostate is found in 70% of patients with inconsiderable BHP and PSA levels above 15 ng/ml. PSA is mainly useful for monitoring patients with carcinoma of the prostate. No patient with BHP had marked elevations of PAP, whereas high PAP levels were found in 26% of patients with carcinoma of the prostate. Eighty-eight per cent of patients with carcinoma of the prostate had increased PAS levels, which were the only finding in 48 cases. No patient with carcinoma of the prostate had increased PAP levels with normal PSA levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acid Phosphatase; Adult; Antigens, Neoplasm; Biomarkers, Tumor; Female; Humans; Male; Middle Aged; Neoplasms; Prognosis; Prostate-Specific Antigen; Prostatic Hyperplasia; Prostatic Neoplasms; Radioimmunoassay

Prostatic acid phosphatase (PAP) was localized in human prostate with a monoclonal antibody prepared against PAP isoenzyme II to determine patterns of its expression in normal, hyperplastic (BPH), and cancerous glands. The monoclonal antibody reacted with both isoenzymes II and IV in immunoblot studies. Formalin-fixed, paraffin-embedded tissue was used from patients who had not been treated with hormones or chemotherapy. In normal glands and BPH, there was marked variation in the intensity of PAP staining in morphologically otherwise similar epithelial cells. There was similar heterogeneity of staining in the adenocarcinomas. Rough quantification of the intensity patterns in the clinical groups indicated a slight shift to more intense staining in BPH and well-differentiated carcinomas but a progressive decline in the PAP staining in the moderately and poorly differentiated tumors. This decrease in intracellular staining with decreasing differentiation is not inconsistent with the clinical observation that serum levels of acid phosphatase generally increase with higher grade and disseminated tumors, since the enzyme is simply more accessible to the circulatory system in those cases. The same decrease may explain the few disseminated tumors that are not associated with elevated serum levels.

Topics: Acid Phosphatase; Adenocarcinoma; Antibodies, Monoclonal; Electrophoresis, Polyacrylamide Gel; Humans; Immunohistochemistry; Immunologic Techniques; Isoenzymes; Male; Prostate; Prostatic Hyperplasia; Prostatic Neoplasms

We reviewed 721 consecutive samples submitted for measurement of prostate-specific antigen (PSA) over five months. We identified three patients with extremely high PSA concentrations: 650, 1840, and 3280 micrograms/L (their acid phosphatase activities were 3.2, 1337, and 2.8 U/L, respectively), and present case reports for the latter two. Serial dilutions of samples obtained from the patient with the highest PSA concentration indicated that the one-step Tandem-PSA assay gave falsely low values for high concentrations of PSA, an observation consistent with the phenomenon of the "hook effect." This effect was not observed when the sample was reanalyzed for PSA by a two-step procedure.

Topics: Acid Phosphatase; Adenocarcinoma; Aged; Antigens, Neoplasm; Bone Neoplasms; False Negative Reactions; Humans; Male; Middle Aged; Prostate-Specific Antigen; Prostatic Neoplasms

We assayed prostatic specific antigen and prostatic acid phosphatase serum levels in 1,383 patients using a double antibody radioimmunoassay (RIA) 125I. Establishing the upper normal limit in 10 ng/ml for prostatic specific antigen and 2.5 ng/ml for prostatic acid phosphatase, the false positive results were only 1.9 and 5.1% in men with nonprostatic benign or malignant pathology and 0 and 2.2% in women, respectively. We detected false positive levels in 3.5 and 4.7% of the patients with noncomplicated benign prostatic hypertrophy, 64.8 and 19.2% in complicated benign prostatic hypertrophy, 24 and 16% in acute prostatitis and 3.3% in chronic prostatitis for both tumoral markers. The sensibility in patients with prostate cancer was 87.2 and 64.1%, respectively, and there was better correlation with prostatic specific antigen than prostatic acid phosphatase levels on tumoral spread and histologic grading. Finally, the clinical efficacy was higher with prostatic specific antigen and it did not increase with the quantification of both tumoral markers.

Topics: Acid Phosphatase; Antigens, Neoplasm; Biomarkers, Tumor; False Positive Reactions; Female; Humans; Male; Prostate-Specific Antigen; Prostatic Hyperplasia; Prostatic Neoplasms; Radioimmunoassay; Reference Values

Three different human lines of prostate carcinoma were successively transplanted on Balb/c nude mice and the serum values of the prostate specific antigen (PSA) and prostatic acid phosphatase (PAP) were determined simultaneously. In a group of the tumor-bearing animals the influence of endocrine manipulation (castration, estradiol) on the serum concentration of these tumor markers was studied. As far as untreated tumor-bearing mice are concerned, the serum values of both PAP and PSA proved to be strictly dependent on the tumor volume measured. In the exponential growth phase of the grafted tumors, linear growth was linked with a correspondingly increasing PAP and PSA serum level of the test animals. A close correlation was found to exist between the two tumor markers; however, the indicator value of PSA was 20 to 50 times higher than that of PAP under the test conditions. PSA determination yielded no false-negative results, if PAP was elevated. PAP determination was false-negative in 21 per cent of cases with measurable tumors, although the serum level of PSA already showed marked elevation. In treated animals both markers were found to decrease. Arrested growth and tumor regression was associated with falling PAP and PSA serum levels or with levels within normal range. The results of this experimental study support the conclusion that prostate specific antigen represents a substantially more sensitive tumor marker than prostatic acid phosphatase.

Topics: Acid Phosphatase; Animals; Antigens, Neoplasm; Biomarkers, Tumor; Carcinoma; Castration; Estradiol; False Negative Reactions; Humans; Male; Mice; Mice, Nude; Neoplasm Transplantation; Prostate-Specific Antigen; Prostatic Neoplasms

The daily variation of serum levels of prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP) was investigated simultaneously in 10 patients with osseous metastatic prostatic cancer, 10 patients with benign prostatic hyperplasia, and 10 volunteers without prostatic disease. Duplicate serum samples were obtained from all patients on the same day at 8 AM, 12 PM, 4 PM, and 8 PM. Statistical analysis (two-factor analysis of variance comparing time period to disease group) of the mean PSA and PAP levels at the four sampling times on all patient groups demonstrated no evidence of circadian rhythmic variation or any other distinct pattern for the observed sample times. Overall, the variability in PSA levels was significantly less than that observed for PAP. There was no significant difference in mean percent variation between patient groups (cancer, benign, and normal prostate glands) for both the PSA and PAP assays. Our data reveal that serum PSA measurements fluctuate unpredictably over the course of a day in patients with and without prostatic disease, but to a lesser extent than that seen for serum PAP values. These findings illustrate the potential inaccuracy of single determinations of serum PAP or PSA levels for monitoring disease recurrence and treatment response in patients with prostate cancer.

Topics: Acid Phosphatase; Aged; Antigens, Neoplasm; Circadian Rhythm; Humans; Male; Middle Aged; Prostate; Prostate-Specific Antigen; Prostatic Diseases; Prostatic Hyperplasia; Prostatic Neoplasms

Urinary transferrin, serum prostatic acid phosphatase (PAP) and prostatic-specific antigen (PSA) concentrations were measured in patients with prostatic cancer, prostatitis, benign prostatic hypertrophy (BPH) and in a control group. In contrast to recently published data it is concluded that urinary transferrin is not suitable as a tumor marker for prostatic carcinoma. Receiver Operating Characteristic curves were constructed to compare the diagnostic value of the different tests at different cutoff values. Sensitivity and specificity of the urinary marker are extremely low compared to the serum markers PAP and especially PSA, making the former not suitable as an additional marker.

Topics: Acid Phosphatase; Antigens, Neoplasm; Biomarkers, Tumor; Humans; Male; Prostate; Prostate-Specific Antigen; Prostatic Hyperplasia; Prostatic Neoplasms; ROC Curve; Transferrin

A correlation between the serum levels of testosterone and the tissular intensity of prostatic acid phosphatase (PAP) and prostate-specific antigen (PSA) in normal prostates has been demonstrated. In prostatic cancer patients, we studied the correlation between the percentage of neoplastic cells secreting PAP and PSA and the response to androgen deprivation, and found no relationship between them. Therefore it is not possible to predict the response to hormone therapy through the grade of tissular PAP or PSA.

Topics: Acid Phosphatase; Aged; Aged, 80 and over; Antigens, Neoplasm; Biomarkers, Tumor; Combined Modality Therapy; Humans; Male; Middle Aged; Orchiectomy; Prostate-Specific Antigen; Prostatic Neoplasms; Testosterone

Variation in serum prostatic acid phosphatase (PAP) after prostatic digital examination was studied in 22 patients, 18 with benign prostatic hyperplasia (BPH), and 4 with prostatic carcinoma. Serum PAP was determined by enzyme immunoassay (EIA) and compared with standard enzymatic assay (EA). Prostatic tissue from transurethral resection (TUR) was subjected to routine pathologic examination and stained for PAP. PAP level increased above reference range and up to several-fold in 12 of 22 patients (54.5%) by EIA and in 22.7 percent by EA. The increase in PAP correlated positively with the prostate size estimated by digital palpation (R = 0.82, P less than 0.001). There was no definite correlation between the histologic parameters studied and the increase in PAP. No day-to-day variation in PAP level was detected in 8 other patients when samples were taken at 7 AM for three successive days. For proper comparison of PAP value, we suggest that sampling time should be fixed and specimens should be taken before prostatic manipulation.

Topics: Acid Phosphatase; Adenocarcinoma; Aged; False Positive Reactions; Humans; Immunoenzyme Techniques; Male; Middle Aged; Prostate; Prostatic Hyperplasia; Prostatic Neoplasms

Basal cell hyperplasia (BCH) is an uncommon proliferative lesion of the prostate gland. We studied ten cases of BCH, one case of an unusual adenoid basal cell tumor (ABT), and one case of a prostatic adenoid cystic carcinoma (ACC), using a panel of antibodies to define the histogenesis of these lesions. Monoclonal antibodies (MoAb) directed against a cytokeratin, which selectively stains basal cells (34 beta E12), and against muscle-specific actin, which stains myoepithelial cells (HHF35), were used. In addition, antibodies directed against prostatic acid phosphatase (PAP), prostate-specific antigen (PSA), S-100 protein, and vimentin were used. In the normal prostate, epithelial cells reacted positively with 34 beta E12, PAP, and PSA, and negatively with the actin, S-100 protein, and vimentin antibodies. In BCH, positive staining was seen for 34 beta E12, PSA, and PAP, with no reactivity for actin, S-100 protein, and vimentin. In ABT and ACC, positive reactivity was demonstrated for all antibodies except actin and vimentin. These findings indicate that the basaloid cells of BCH, ABT, and ACC are derived from basal cells of the normal prostate gland and suggest a continuum among the three lesions. The presence of S-100 protein in ABT and ACC may be related to the lack of this antigen's specificity for myoepithelial cells. The absence of reactivity with the HHF35 MoAb supports our belief that the S-100 positivity does not necessarily indicate myoepithelial cell differentiation.

Topics: Acid Phosphatase; Actins; Carcinoma, Adenoid Cystic; Carcinoma, Basal Cell; Humans; Immunoenzyme Techniques; Keratins; Male; Prostatic Hyperplasia; Prostatic Neoplasms; S100 Proteins; Vimentin

The levels of prostatic acid phosphatase (PAP), gamma-seminoprotein (gamma-Sm) and prostate specific antigen (PA) were determined in the serum of 200 untreated patients 28 patients with reactivated prostatic cancer and 179 patients with benign prostatic hypertrophy (BPH) from 1979 to 1987. PAP and gamma-Sm were determined using an Eiken and Chugai kit, respectively and PA was assayed using an Eiken or Travenol kit. The sensitivity of PAP, gamma-Sm and PA respectively in the untreated prostatic cancer cases was 0, 0% and 67%, for Stage A1, 25, 17 and 100% for Stage A2, 23, 50 and 60% for Stage B, 62, 81 and 94% in Stage C, 58, 67 and 90% for Stage D1, 86, 88 and 100% for Stage D2. The specificity of PAP, gamma-Sm and PA is 89, 69 and 43%, respectively. The efficiency of PAP was the highest at all stages as a whole, but when compared at each stage, gamma-Sm was the highest at Stages B and C. The sensitivity of simultaneous assays of PAP and gamma-Sm was slightly increased, but sensitivity was not increased by simultaneous use of three markers. The efficiency of a simultaneous assay was lower than that of a single assay with PAP. However, combined determination of gamma-Sm or PA with PAP was found to be useful for monitoring the clinical course of the reactivated patients. Correlation between PAP and PA levels was high, but that between gamma-Sm and PA levels was low. There was no correlation between PAP and gamma-Sm levels. In conclusion, PAP is the most valuable marker for prostatic cancer, and gamma-Sm is of value for use in combination with PAP. However, an additional PA assay was not found to be of advantage.

Topics: Acid Phosphatase; Aged; Aged, 80 and over; Antigens, Neoplasm; Biomarkers, Tumor; Blood Proteins; Humans; Male; Middle Aged; Neoplasm Staging; Predictive Value of Tests; Prostate; Prostate-Specific Antigen; Prostatic Hyperplasia; Prostatic Neoplasms; Prostatic Secretory Proteins; Seminal Plasma Proteins

Serum prostatic acid phosphatase and prostate-specific antigen have been measured in a group of 106 cases of newly diagnosed prostate cancer. The serum levels of the tumour markers have been correlated with the clinical and ultrasound staging of the prostate cancer at diagnosis. All patients were managed by a deferred treatment policy. Patients without detectable metastases at presentation have been assessed after a period of 2 years to determine if the level of serum tumour markers at diagnosis could predict subsequent disease progression. The study has demonstrated that a combination of immunologically measured acid phosphatase and prostate-specific antigen is the best method of assessing the prognosis of an individual prostate cancer at the time of presentation.

Topics: Acid Phosphatase; Antigens, Neoplasm; Biomarkers, Tumor; Follow-Up Studies; Humans; Male; Neoplasm Staging; Prognosis; Prostate-Specific Antigen; Prostatic Neoplasms; Time Factors

The clinical usefulness of prostate specific antigen (PSA) and prostatic acid phosphatase (PAP) activity measurements has been compared in 45 patients with benign prostatic hyperplasia (BPH) and 132 patients with prostatic carcinoma (PC), 21 of whom had metastatic disease (MPC) and 111 of whom had intracapsular cancer. No BPH patient had increased PAP but 47% had increased PSA. Of the PC patients only 27% had increased PAP and 70% increased PSA. All of the MPC patients had increased PSA but only 62% had increased PAP. Increased PAP was found only in MPC but increased PSA was also found in BPH. In identifying PC, the predictive value of an increased PSA concentration is 83% and an increased PAP activity is 100%. On the other hand, the predictive value of a normal PSA concentration is 51% and of a normal PAP activity only 34%. As the PAP test is much less efficient than the PSA test, it should be discontinued.

Topics: Acid Phosphatase; Aged; Aged, 80 and over; Antigens, Neoplasm; Biomarkers, Tumor; Humans; Male; Middle Aged; Predictive Value of Tests; Prostate-Specific Antigen; Prostatic Hyperplasia; Prostatic Neoplasms

Measurements of prostatic acid phosphatase (PAP), prostatic antigen (PA) and gamma-seminoprotein (gamma-Sm) have been found to be clinically useful in the diagnosis of prostatic carcinoma, but, the usefulness of simultaneous measurement has not yet been elucidated. We determined the clinical significance of simultaneous measurement of these markers, especially, the additional measurement of PA or gamma-Sm to PAP in prostatic carcinoma. Each measurement of PAP, PA and gamma-Sm yielded a very low "false" positive rate (0-6.5%) in patients with non-prostatic urogenital disease or benign prostatic hypertrophy (BPH), which was consistent with the results reported so far by other researchers. Eighteen patients with newly diagnosed prostatic carcinoma of a low stage showed a positive rate of PAP in 16.7%, PA in 33.3% and gamma-Sm in 38.9%. Forty patients having a high stage had a positive rate of 67.5% for each of the markers. In patients with BPH, the positive rate was elevated in only 2.6, 5.2 or 3.9% by the additional measurement of PA or gamma-Sm to PAP, or that of gamma-Sm to PA, respectively. This implied that the additional measurement of other markers to PAP or PA produced only a low elevation of the "false" positive rate. The positive rate in patients with prostatic carcinoma of low stage was increased by the additional measurement of PA or gamma-Sm to PAP or that of gamma-Sm to PA. This suggests that in patients with low stage carcinoma, assay with these combinations would be clinically useful to monitor the patient's clinical course.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acid Phosphatase; Antigens, Neoplasm; Biomarkers, Tumor; Blood Proteins; Diagnosis, Differential; Humans; Male; Prostate-Specific Antigen; Prostatic Hyperplasia; Prostatic Neoplasms; Prostatic Secretory Proteins; Seminal Plasma Proteins

Topics: Acid Phosphatase; Aged; Aged, 80 and over; Antigens, Neoplasm; Biomarkers, Tumor; Humans; Male; Prostate-Specific Antigen; Prostatic Neoplasms; Radioimmunoassay

Topics: Acid Phosphatase; Adult; Antigens, Neoplasm; Biomarkers, Tumor; Female; Humans; Immunoenzyme Techniques; Male; Middle Aged; Prostate-Specific Antigen; Prostatic Neoplasms; Prostatic Secretory Proteins; Proteins; Seminal Plasma Proteins

Between June, 1986 and December, 1987, the serum gamma-Sm and PAP was measured in 29 men with untreated prostatic cancer, 45 with treated prostatic cancer (32 were well-controlled and 13 poorly controlled), 82 with benign prostatic hypertrophy and 10 with other urological diseases. All of the patients with prostatic cancer had histologically proven disease. Enzyme immunoassay for gamma-Sm and radioimmunoassay for PAP were used. The cut-off value for gamma-Sm was 4 ng/ml and that for PAP was 3 ng/ml. The mean values of gamma-Sm and PAP were statistically high in the untreated group and also in poorly-controlled group. In the untreated group, the rate of positivity for gamma-Sm and for PAP were 69% respectively and 83% of the patients had elevated values for either or both of these markers. In clinical stage A and B, gamma-Sm and PAP values were within the normal limit, however the concentrations of mean gamma-Sm and PAP correlated well with the stage of disease. In the poorly-controlled group, positive gamma-Sm values were detected in 75% and PAP in 67%, whereas almost all of the patients had normal values for these markers in the well-controlled group. In prostatic hypertrophy, elevated gamma-Sm values were detected in 15% and elevated PAP values in 6%. After the onset of treatment, elevated values were normalized in 66.7% of the patients for gamma-Sm and in 68.4% for PAP. In the untreated group, gamma-Sm tended to show a more prompt response. In the ill-controlled group, gamma-Sm and PAP returned to normal in 50% of the patients. gamma-Sm and PAP values were well correlated with the course of the prostatic cancer and the clinical usefulness became more obvious with a combination of these markers.

Topics: Acid Phosphatase; Adenocarcinoma; Aged; Aged, 80 and over; Biomarkers, Tumor; Blood Proteins; Humans; Immunoenzyme Techniques; Male; Middle Aged; Predictive Value of Tests; Prostate; Prostatic Hyperplasia; Prostatic Neoplasms; Prostatic Secretory Proteins; Radioimmunoassay; Seminal Plasma Proteins

The serum prostate specific antigen (PA) of the patients with prostatic cancer were determined with 3 assay kits, the Diagnostic Products Cooperation (DPC) kit, the Eiken kit and the Dainippon Pharmaceutical Co. (MARKIT F) kit. The first 2 assay kits involve radioimmunoassay and the latter EIA. For comparison, prostatic acid phosphatase (PAP) and gamma-seminoprotein (gamma-Sm) were determined using an Eiken kit and Chugai kit. Efficiency of the DPC kit, Eiken kit and the MARKIT F kit for untreated prostatic cancer was 26, 25 and 36%, respectively. The PA level measured using the Eiken kit and the MARKIT F kit both well correlated to the PAP level, but with the DPC kit correlation was slightly low. The PA level measured using the 3 different kits correlated poorly with the gamma-Sm level. The PA values obtained with 3 different assays from patients with prostatic cancer were highly correlated, but showed great differences in the values measured. When the standards used in the DPC kit were analyzed by the Eiken kit, the DPC standards as measured by the Eiken kit had only about half of their assigned values. The same standards were analyzed by the MARKIT F kit, the standards yielded measured values about one third of their assigned values. When the standards used in the MARKIT F kit were analyzed by the Eiken kit, the MARKIT F standards yielded measured values about 2.5 fold of their assigned values. The differences between the values obtained with the 3 assay kits presented a serious problem in clinical use of PA. Standardization of these assay kits will be awaited.

Topics: Acid Phosphatase; Antigens, Neoplasm; Biomarkers, Tumor; Blood Proteins; Evaluation Studies as Topic; Humans; Immunoenzyme Techniques; Male; Middle Aged; Predictive Value of Tests; Prostate; Prostate-Specific Antigen; Prostatic Hyperplasia; Prostatic Neoplasms; Prostatic Secretory Proteins; Radioimmunoassay; Reagent Kits, Diagnostic; Seminal Plasma Proteins

Blood samples from 500 patients with clinical prostatic symptoms were radioimmunoassayed with prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP) kits. On the basis of histological data, directed by PSA results and other investigations, 200 prostatic cancers (adenocarcinomas), 276 benign prostatic hypertrophy (BPH), 16 cases of prostatitis, 5 cancers of the bladder, and 3 prostatodynias were diagnosed. All of the serum samples from prostatic cancer patients showed elevated PSA levels at diagnosis, whereas about 70% of these showed normal PAP values. The sensitivity of the PSA assay is 100% when 2.5 ng/ml is taken as the upper limit of normal. However, the specificity and the positive predictive value are better at 10 ng/ml: 99 and 79%, respectively. High PSA values alerted the clinician when diagnosing a cancer without symptoms on rectal or ultrasonographic examination (3%). In BPH, when the PSA level is between 2.5 and 10 ng/ml, a PSA control must be performed within 2 months. If PSA increases above 10 ng/ml, the risk of cancer has to be considered. In the follow-up, PSA is a better marker than PAP to detect disease progression and seems to constitute an evolutive tumor mass index. PSA is the most sensitive, the earliest, and the most prognostically reliable marker for diagnosis and follow-up of prostate cancer patients.

Topics: Acid Phosphatase; Aged; Antigens, Neoplasm; Biomarkers, Tumor; Humans; Male; Neoplasm Metastasis; Neoplasms, Hormone-Dependent; Prostate; Prostate-Specific Antigen; Prostatic Hyperplasia; Prostatic Neoplasms; Prostatitis; Radioimmunoassay

A comparative study was performed on the usefulness of prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP) in control subjects (69), benign prostatic hypertrophy (BPH) patients (150), and patients with prostatic carcinoma (113) in a urology department. We establish, as others, the greater clinical sensitivity of PSA and its effectiveness as a prognostic tool in the evaluation of prostatic cancer therapy and in the early detection of residual tumor following radical prostatectomy. However, patients are admitted to our department with more severe and complicated benign prostatic pathology and urinary dysfunctions, which decreases the specificity of the PSA test to 30% (N = 2.7 ng/ml). A cutoff threshold of 50 ng/ml becomes necessary to maintain a 90% positive predictive value. The combination of PSA sensitivity (96%) and PAP specificity (95%) enabled a better definition of the high-risk subpopulation among noncancer patients and, in addition, was a help for differential diagnosis, confirmation of advanced stages of prostatic cancer, and selection of low-stage prostatic cancer candidates undergoing radical prostatectomy. Routine serum PSA measurements in the population of patients consulting a urology department will no doubt bring about a new approach to the management of prostate cancer.

Topics: Acid Phosphatase; Adult; Aged; Antigens, Neoplasm; Biomarkers, Tumor; Female; Humans; Male; Middle Aged; Neoplasms, Hormone-Dependent; Prognosis; Prostate; Prostate-Specific Antigen; Prostatectomy; Prostatic Hyperplasia; Prostatic Neoplasms; Sensitivity and Specificity

Coupled prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP) measurements (using the radioimmunoassay method) were carried out on 220 controls, 33 patients with prostatic hyperplasia, and 71 with carcinoma. The mean PSA value was 3.70 +/- 3.31 ng in the controls. A level of 10 ng was adopted as the upper limit of normal. Four of the eight cases of prostatic hyperplasia with a high PSA level (between 10 and 25 ng) underwent surgery. Histological tests confirmed benign hyperplasia. In the localized cancers, the PSA level was normal. In the metastatic cancers, PSA proved to be more sensitive than PAP. Thus, PSA is of little use in the early diagnosis of cancer; its systematic measurement as a means of cancer screening for the general public may even be misleading.

Topics: Acid Phosphatase; Adult; Aged; Aged, 80 and over; Antigens, Neoplasm; Biomarkers, Tumor; Carcinoma; Humans; Male; Middle Aged; Neoplasm Metastasis; Neoplasms, Hormone-Dependent; Prostate; Prostate-Specific Antigen; Prostatic Hyperplasia; Prostatic Neoplasms

Prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP) levels were determined in 241 patients attending the Department of Urology. The population consisted of 140 prostate cancer patients (34 newly diagnosed and 106 under treatment) and 101 patients with benign prostatic hypertrophy (BPH). The diagnostic values of PAP measured by enzymatic assay (EA) and by immunoenzymetric assay (IEMA) appeared to be similar. Elevated PAP (IEMA) levels were found in 10% of the patients with BPH and in 38% of the cancer patients. PSA was measured by immunoradiometric assay (IRMA) and receiver operating characteristic curves were constructed to compare the diagnostic benefits of different cutoff values. PSA (10 micrograms/L) reached a specificity of 88% and a sensitivity of 46%. With a cutoff value of 2.7 micrograms/L, the sensitivity increased to 64%, whereas the specificity fell to 58%. It is concluded that PSA is the most useful marker as a screening test.

Topics: Acid Phosphatase; Antigens, Neoplasm; Biomarkers, Tumor; Humans; Immunoenzyme Techniques; Male; Neoplasm Staging; Neoplasms, Hormone-Dependent; Prostate; Prostate-Specific Antigen; Prostatic Hyperplasia; Prostatic Neoplasms; Sensitivity and Specificity

Prostate-specific antigen (PSA) was compared to prostatic acid phosphatase (PAP) in patients with prostatic cancer suspected to have bone metastases. Bone scans were classified according to metastatic skeletal involvement. The sensitivity of PSA in predicting the presence of metastatic disease (68%) was better than that of PAP (53%). Specificity was 79% for PSA and 90% for PAP. Thirty-five patients had a positive PSA level and a normal scintigraphy (false-positive); 14 of them had only endoscopic prostate resection. Thirty-eight patients underwent a further exploration 3-18 months later. PSA level during disease was correlated to scintigraphy in 32 of 38 patients.

Topics: Acid Phosphatase; Aged; Aged, 80 and over; Antigens, Neoplasm; Biomarkers, Tumor; Bone Neoplasms; Follow-Up Studies; Humans; Male; Middle Aged; Neoplasms, Hormone-Dependent; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Radionuclide Imaging; Sensitivity and Specificity

Prostate-specific antigen (PSA) was assayed retrospectively in 131 prostate cancer patients. Pretreatment levels at primary tumor diagnosis were above 5 ng/ml in 13/16 (81%) of stage B and C patients and in 28/28 (100%) of stage D (D1 and D2) patients. At the discovery of metastasis in treated patients, they were above this value in 12/17 (71%) of patients. To determine the value of PSA assays when physical exams were negative, 52 patients were reevaluated at a maximum interval of 12 months as a function of their initial PSA concentration. When the initial PSA was negative, there was no clinical evolution during the next 6 months; when PSA was positive, patients had a 55% risk of progression in the next 4 months. All PSA assays were coupled with prostatic acid phosphatase (PAP) measurements. No PAP values were positive when PSA was negative.

Topics: Acid Phosphatase; Aged; Aged, 80 and over; Antigens, Neoplasm; Biomarkers, Tumor; Female; Follow-Up Studies; Humans; Male; Middle Aged; Neoplasm Metastasis; Neoplasm Staging; Neoplasms, Hormone-Dependent; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Retrospective Studies; Sensitivity and Specificity

The efficiency of the tumor markers prostatic acid phosphatase (PAP), prostate-specific antigen (PSA), neopterin, and osteocalcin was tested with regard to their ability to predict cancer death within 2 years plus survival beyond 2 years in a series of patients with newly diagnosed prostate cancer. For all markers, an elevated level suggested a tumor with a worse prognosis. Moreover, the extent to which the level was increased carried additional information. The prognostic efficiency was routinely improved by selecting cutoff levels higher than the standards suggested by the radioimmunoassay (RIA) kit manufacturers. Seventy-four percent of the patients with elevated levels of neopterin were still alive after 2 years when 8 nmol/L was selected as the upper normal value compared to only 43% at 12 nmol/L. At a cut-off value of 3 micrograms/L for osteocalcin, 79% of the patients with elevated levels were still alive after 2 years compared with only 20% when 7 micrograms/L was selected. Such adjustments to higher cutoff levels could be made without increasing the number of "false-negatives." The efficiency of PAP to predict short-term prognosis was poor at the standard cutoff level of 1.9 microgram/L. Not until 20 micrograms/L was selected did the efficiency exceed 80%. PSA was highly sensitive but little specific at any of the cutoff levels tested with regard to ability to indicate prognosis.

Topics: 1-Carboxyglutamic Acid; Acid Phosphatase; Antigens, Neoplasm; Biomarkers, Tumor; Biopterins; Calcium-Binding Proteins; Estradiol; Estradiol Congeners; Ethinyl Estradiol; Humans; Male; Neoplasms, Hormone-Dependent; Neopterin; Orchiectomy; Osteocalcin; Prognosis; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Reference Values

Prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP) have been evaluated in patients with prostatic cancer. All patients, who participated in a phase III trial (n = 110), had disseminated disease and received first line endocrine treatment of either orchidectomy or a monthly injection of a depot luteinizing hormone-releasing hormone analogue (Zoladex). Serum samples were analyzed for PSA and PAP at 0, 3, 6, and 12 months and patients were clinically assessed at 6 and 12 months. At diagnosis, 72 and 97% of all patients had elevated PAP and PSA concentrations (greater than 4 ng/ml), respectively. Patients with progressive disease had significantly higher PSA and PAP levels at both assessments. A small number of patients in the "complete remission" group had both PSA and PAP levels within the normal range after 3 months of treatment. Similarly, both PSA and PAP levels steadily declined in the group of patients who had partial regression of the disease. The patients with stable disease, however, had a significant rise only in their PSA levels at the 12-month assessment. This data suggest that PSA is more sensitive than PAP in those patients who have a "slow progression" of the disease.

Topics: Acid Phosphatase; Antigens, Neoplasm; Biomarkers, Tumor; Follow-Up Studies; Humans; Male; Neoplasms, Hormone-Dependent; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Remission Induction; Retrospective Studies

To evaluate a possible direct cytotoxic effect of diethylstilbestrol diphosphate (DESDP) in the treatment of prostate cancer we exposed three prostatic carcinoma cell lines (LNCaP, DU 145, and PC-3), 2 nonprostatic neoplastic cell lines (KB and EJ), and one nontransformed cell line (MRC-5) to diethylstilbestrol (DES), diethylstilbestrol monophosphate, and DESDP at levels occurring in patients' sera during p.o. DES therapy (2 to 5 ng/ml) or DESDP infusions (1 to 20 micrograms/ml), respectively. With 5 ng/ml of DES no effect was seen in LNCaP cells, even after 14 days of exposure. In contrast, drug levels attained during DESDP infusions showed marked, dose-dependent cytotoxicity towards all cell lines under study. Prostatic cells were not exceptionally sensitive. High-dose DES slightly stimulated the synthesis of prostatic acid phosphatase in LNCaP cells. Formation of foci of polygonal cells was induced by 5 micrograms/ml of DES in cultures of MRC-5 fibroblasts. We conclude that, at high doses, DES liberated from DESDP acts upon a regulatory or metabolic mechanism common to many if not all human cells. Preferential sensitivity of prostate cancer cells in vivo may be due to high local phosphatase activity and/or DES accumulation in prostatic tissue.

Topics: Acid Phosphatase; Antineoplastic Agents; Diethylstilbestrol; Humans; Male; Phosphoric Monoester Hydrolases; Prostate; Prostatic Neoplasms; Tumor Cells, Cultured

In a comparative study, we determined the mean serum concentrations of immunoassayable prostatic acid phosphatase (PAP), tartrate-inhibited phosphatase (TP), total acid phosphatase (AcP), and alkaline phosphatase (AP) in different clinical subgroups of patients with histologically proved prostatic carcinoma (PCA). The subgroups were compared with each other and with a reference group of males apparently free of any prostatic disorder. In addition, clinical sensitivities, specificities, and predictive values were calculated to assess the diagnostic value of the different assays. The main results were: (1) Serum PAP concentration measured by immunologic methods best reflected the tumor mass, the presence or absence of metastases, the histologic grade, and the therapeutic efficiency (response) in the patients. (2) The differences in biochemically determined serum TP concentrations were less clear-cut. (3) The serum concentrations of the nonspecific phosphatases AcP and AP were highly elevated in patients with progressed PCA; AP was the highest in patients with palpable tumors and metastases. (4) The sensitivities of each phosphatase were too low for detection of early PCA stages. In conclusion, immunoassayable PAP appears to be the best parameter to monitor advanced PCA disease, and AP may be a useful auxiliary parameter in metastatic PCA.

Topics: Acid Phosphatase; Alkaline Phosphatase; Carcinoma; Humans; Male; Phosphoric Monoester Hydrolases; Prostate; Prostatic Neoplasms

Topics: Acid Phosphatase; Androgen Antagonists; Bone Neoplasms; Cyproterone; Cyproterone Acetate; Follow-Up Studies; Humans; Male; Neoplasm Staging; Prostatic Neoplasms; Radionuclide Imaging; Retrospective Studies

Cyproterone acetate is a steroidal antiandrogen with weak progestational activity that results in the partial suppression of pituitary gonadotropin. We demonstrate that the associated decrease in serum testosterone is more complete and prolonged if cyproterone acetate (200 mg. daily) is combined with a low dose of diethylstilbestrol (0.1 mg. daily). The effectiveness of the combination in the treatment of prostatic carcinoma was investigated in 51 patients with stage D2 malignancy. From an initial concentration of 360 +/- 23 ng. per dl. (mean +/- standard error), serum testosterone decreased to 56 +/- 5 ng. per dl. after 1 week and reached a plateau of approximately 30 ng. per dl. after 2 months. This was accompanied by a decrease in serum prostatic acid phosphatase from a mean starting concentration of 43 +/- 11 ng. per ml. to a low of 3 +/- 1 ng. per ml. at 12 months; the proportion of normal values increased from 10 to 80 per cent. A complete response was observed in 7 patients (13 per cent), partial response in 35 (69 per cent) and stable disease in 8 (16 per cent), yielding an over-all objective response rate of 98 per cent (1980 National Prostatic Cancer Project criteria). The actuarial median time to progression was 17 months and the median survival time was 23.5 months. In 26 patients who subsequently had signs of progressive carcinoma the relapse rate in bone (85 per cent) far exceeded that in nonskeletal sites (23 per cent). The incidence of cardiovascular toxicity was 12 per cent. These results indicate that cyproterone acetate and low dose diethylstilbestrol may be co-administered to achieve a synergistic and potent androgen withdrawal effect in the treatment of advanced prostatic carcinoma.

Topics: Acid Phosphatase; Adult; Aged; Aged, 80 and over; Androgen Antagonists; Antineoplastic Combined Chemotherapy Protocols; Carcinoma; Cyproterone; Cyproterone Acetate; Diethylstilbestrol; Drug Evaluation; Drug Synergism; Gonadotropins, Pituitary; Humans; Male; Middle Aged; Pilot Projects; Prostatic Neoplasms; Testosterone

Monoclonal antibodies of IgG1 subclass raised against purified human prostate-specific acid phosphatase were subjected to different procedures to produce F(ab')2 fragments suitable for radioimaging of prostatic cancer, following derivatization and labeling with radionuclides. The main aim was to obtain highly purified fragments with preserved immunological activity. Optimized pepsin digestion led to the formation of mainly F(ab')2 and Fab fragments, and, following Sephacryl S-200 gel filtration, the yield of pure F(ab')2 fragments was 24 +/- 11% of the theoretical maximum. After papain digestion in the absence of thiols, no formation of Fab fragments was observed, and the F(ab')2 fragments formed could be efficiently separated from Fc fragments by chromatofocusing or ion exchange chromatography. The yield of F(ab')2 fragments from papain digestion was 50 +/- 5% of the theoretical maximum. Both the above procedures gave F(ab')2 fragments with immunoreactivity and affinity identical to those of the precursor IgG1, despite the fact that isoelectric focusing profiles of the two F(ab')2 preparations differed, suggesting different digestion sites.

Topics: Acid Phosphatase; Animals; Antibodies, Monoclonal; Antibody Affinity; Antigen-Antibody Reactions; Binding Sites, Antibody; Humans; Immunoglobulin Fab Fragments; Immunoglobulin G; Male; Mice; Organ Specificity; Papain; Pepsin A; Prostatic Neoplasms; Radionuclide Imaging

A slow-release formulation of the luteinizing hormone releasing hormone (LH-RH)analog(TAP-144-SR) was administered in 6 cases of prostatic cancer. Five were untreated cases, 3 of moderately-differentiated and 2 of poorly-differentiated cancers (four D2 and one C, NX), the other (D2) was under control by another LH-RH analog. The plasma level of luteinizing hormone and follicle stimulating hormone fell below normal, and the plasma testosterone was less than 1 ng/ml by four weeks after start of treatment. According to the National Prostatic Cancer Project Criteria, 2 of the untreated cases showed a partial response and 3 of the untreated ones showed a stable response, one of which underwent transurethral resection later. The pretreated case still continued controlled more than 4 months. No side effect was noticed.

Topics: Acid Phosphatase; Aged; Aged, 80 and over; Antineoplastic Agents; Delayed-Action Preparations; Drug Evaluation; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Humans; Leuprolide; Luteinizing Hormone; Male; Prostate; Prostatic Neoplasms; Remission Induction; Testosterone

Leuprolide, a synthetic LHRH analog, inhibited growth of the Dunning R 3327 androgen-sensitive rat prostatic tumor and induced weight loss in male accessory sex organs. The relationship between the mode of administration and efficiency of the treatment was examined. Maintenance of the drug level in vivo seemed to be one of the important factors in the suppression of tumor growth, while a decrease in the weight of the accessory sex organs was mainly dependent on the dose administered. No treatment with leuprolide surpassed the effect caused by castration. Cytosolic androgen receptor and acid phosphatase activity in the tumor tissues were not changed significantly after treatment with leuprolide.

Topics: Acid Phosphatase; Animals; Cytosol; Genitalia, Male; Gonadotropin-Releasing Hormone; Leuprolide; Male; Neoplasm Transplantation; Orchiectomy; Organ Size; Prostatic Neoplasms; Rats; Rats, Inbred Strains; Receptors, Androgen; Testis; Testosterone

Acid phosphatase in serum has been used for half a century as a circulating marker in prostatic disease. Recently new proteins have been introduced as potential markers to replace acid phosphatase. Neither acid phosphatase nor the alternative markers are of clinical value in the detection and classification of prostatic neoplasms, though they are of some value for monitoring the course of disease and its response to treatment. Important questions concerning the biology of the tumour markers in regard to site of origin, secretion and turnover remain to be answered.

Topics: Acid Phosphatase; Biomarkers, Tumor; Humans; Male; Monitoring, Physiologic; Prostate; Prostatic Neoplasms

Limited clinical stage C (T3 NX M0) disease can be treated surgically, and morbidity can be acceptable. When appropriate adjuvant therapy (orchiectomy and/or radiation) is administered, residual cancer can be controlled locally for at least a limited period. The incidence of local progression in pathologic stage C or D1 disease may be negligible after early adjuvant orchiectomy and/or radiation treatment. The combination of immediate orchiectomy and radical prostatectomy has been shown to limit progression significantly (P = .0009) in many patients with D1 (T0-3 N1,2 M0) disease. However, some patients do not respond to this combination treatment, which suggests that systemic dissemination of heterogeneous tumor cells is unresponsive to adjuvant androgen ablation therapy. The DNA ploidy pattern may be a valuable predictor of disease outcome after treatment in stage D1 disease. Other pathologic variables (including acid phosphatase levels) have not been useful in predicting disease outcome or treatment response. Finally, patients with limited clinical stage C disease and those with pathologic C or D1 disease should be enrolled in a prospective randomized protocol so that the possible beneficial effects of adjuvant treatment programs can be evaluated. Apart from the usual pathologic variables and prostate-specific antigen testing, the DNA pattern should be included as a stratification factor.

Topics: Acid Phosphatase; Adenocarcinoma; Adult; Aged; Combined Modality Therapy; Follow-Up Studies; Humans; Lymph Node Excision; Male; Middle Aged; Orchiectomy; Prostatectomy; Prostatic Neoplasms

Clinical and statistical investigations were performed on 157 patients with prostate carcinoma in the Third Teaching Hospital, Normal Bethune University experienced between January, 1950 and June, 1986. The number of patients with prostate carcinoma among other hospitalized patients showed a recent gradual increase. The patient's age at the time the disease was first diagnosed was most frequently between 60 and 69 years old with an average age of 63.3 years. Dysuria was the most prominent symptom, followed by frequency, retention and macroscopic hematuria. Duration between initial symptom and diagnosis was one to two years in most patients. The prostatic abnormality could be detected by rectal examination in all patients. Elevation of serum acid phosphatase was found in 24.4%. Such elevation was evident in 52.2% of the patients with metastatic lesions, compared to 14.4% of those without metastasis. Fourteen patients had metastasis to bone (8.9%), 13 to lymph nodes, 2 to lung and one to liver. According to the staging diagnosis, 19 patients (12.1%) had stage A, 78 patients (49.7%) had stage B, 20 patients (12.7%) had stage C and 40 patients (25.5%) had stage D carcinoma. Histological findings in 57 patients indicated adenocarcinomas; 39 cases (68.4%) were poorly differentiated, 12 cases (21.2%) were moderately differentiated and 6 cases (10.5%) were well differentiated. Modality of treatment was total prostatectomy in 2 cases (1.3%), antiandrogen therapy (orchiectomy and/or Stilbestrol) in 122 cases (77.7%), subcapsular prostatectomy in 7 cases (4.5%), symptomatic treatment in 5 cases and no treatment in 23 cases (14.6%).

Topics: Acid Phosphatase; Adenocarcinoma; Adult; Aged; Aged, 80 and over; China; Combined Modality Therapy; Humans; Male; Middle Aged; Neoplasm Metastasis; Neoplasm Staging; Prostatic Neoplasms; Urination Disorders

This study investigated the effect of metastatic prostatic carcinoma on bone density. Thirty patients underwent a lumbar spine scan with a dual photon absorptiometer. Of these patients, 9 had proven skeletal metastatic deposits in the area being investigated. Comparison of results with a non-matched control population with proven benign prostatic histology showed a significantly elevated linear bone mineral content (BMC) in the disease group. Patients scanned after a 3- or 6-month period of hormonal therapy demonstrated a rise in BMC values, although the trend was not statistically significant. Indices of calcium metabolism have also been investigated.

Topics: Acid Phosphatase; Aged; Aged, 80 and over; Alkaline Phosphatase; Bone and Bones; Bone Neoplasms; Calcium; Cyproterone; Diethylstilbestrol; Humans; Male; Middle Aged; Minerals; Prostatic Neoplasms

We investigated retrospectively 91 patients with prostatic carcinoma diagnosed cytologically between 1978 and 1979. Of the patients 57 had no metastases (M0) at presentation. The majority of the patients without metastases had well or moderately well differentiated carcinoma. Of 18 patients with poorly differentiated carcinoma 17 had metastases at presentation. The patients without metastases were left untreated, while those with metastases received active antitumor treatment. Local progression and/or development of metastases during surveillance occurred in 24 patients (42 per cent) and antitumor treatment was initiated. Mean observation time in the group untreated throughout observation was 47 months. Mean interval to progression in the patients treated subsequently was 31 months. In the surveillance group no difference in mean interval to progression, frequency of local progression, development of metastases or death rate of prostatic carcinoma was found when the patients with initially well and moderately well differentiated carcinoma were compared. Therefore, in our study initial cytological grade failed to predict a difference in progression in patients with well and moderately well differentiated prostatic carcinoma. Since almost all patients with poorly differentiated carcinoma had metastases at presentation a poor differentiation seems to predict a worse prognosis compared to well and moderately well differentiated tumors.

Topics: Acid Phosphatase; Aged; Aged, 80 and over; Bone and Bones; Carcinoma; Humans; Male; Middle Aged; Neoplasm Metastasis; Neoplasm Staging; Prostatic Neoplasms; Radionuclide Imaging; Retrospective Studies

Plasma levels of urokinase-type plasminogen activator have been investigated in 80 patients with prostatic carcinoma by means of a radioimmunoassay. A total of 30 patients with disseminated prostatic carcinoma had significantly elevated levels of urokinase-type plasminogen activator, whereas the plasma levels in patients without metastases did not differ from a healthy age matched control group. Sensitivity of elevated urokinase-type plasminogen activator levels in patients with prostatic carcinoma for the presence of metastases was 80 per cent. Therefore, urokinase-type plasminogen activator appears to be a reliable marker for the formation of metastases in prostatic carcinoma.

Topics: Acid Phosphatase; Aged; Aged, 80 and over; Alkaline Phosphatase; Biomarkers, Tumor; Carcinoma; Humans; Male; Middle Aged; Neoplasm Metastasis; Prognosis; Prostatic Neoplasms; Radioimmunoassay; Urokinase-Type Plasminogen Activator

Acid phosphatase levels were determined using both an enzymatic method (32 cases) and radioimmunoassay (35 cases) in 35 patients with clinically localised prostatic cancer. All patients underwent total prostatectomy and pelvic lymphadenectomy. In cases of intracapsular prostatic cancer the level of prostatic acid phosphatase (PAP) measured by radioimmunoassay was 1.4 +/- 0.8 micrograms/l. In patients with either local extraprostatic disease or pelvic lymph node metastases the mean level of PAP was 3.5 +/- 2.8 micrograms/l. The difference was statistically significant. The specificity, sensitivity and accuracy of an elevated PAP (greater than 3.0 micrograms/l) in revealing extraprostatic extension of clinically localised prostatic cancer were 100, 37 and 66% respectively. When the enzymatic method was used, the level of acid phosphatase was elevated (greater than 13 u/l) in only 1 case. The specificity, sensitivity and accuracy of the enzymatic method were 100, 6 and 47% respectively. Elevation of PAP predicts, with a high degree of probability, either local extension outside the prostate or lymph node metastases. A normal PAP does not exclude extraprostatic extension of prostatic cancer.

Topics: Acid Phosphatase; Aged; Clinical Enzyme Tests; Humans; Male; Middle Aged; Neoplasm Metastasis; Neoplasm Staging; Predictive Value of Tests; Preoperative Care; Prostatectomy; Prostatic Neoplasms; Radioimmunoassay

Topics: Acid Phosphatase; Antibodies; Antibodies, Monoclonal; Biomarkers, Tumor; Humans; Male; Prognosis; Prostatic Neoplasms

Forty-four patients with metastatic cancer of the prostate that had failed conventional hormonal manipulation were treated with high-dose ketoconazole (600-1,200 mg/day). All patients had castrate serum concentrations of testosterone prior to therapy. All of the patients had been assessed by the criteria of the National Prostatic Cancer Project and been categorized as progressing. Over 50% of the patients were recategorized as having stable disease. The majority of the patients showed marked subjective improvement in pain on this therapy. Objective responses were noted but were not consistently seen. Side effects were common but tolerable. The median time of survival was 73.3 weeks. Ketoconazole may be a useful palliative adjunct in the treatment of hormone refractory prostatic cancer.

Topics: Acid Phosphatase; Aged; Aged, 80 and over; Alkaline Phosphatase; Humans; Ketoconazole; Male; Middle Aged; Neoplasm Metastasis; Neoplasms, Hormone-Dependent; Pain; Prostatic Neoplasms; Remission Induction

Serum contents of prostatic acid phosphatase, neopterin, osteocalcin, tissue polypeptide antigen and CA-50 were measured before onset of treatment in 83 patients suffering from prostatic carcinoma. In an attempt to identify patients with poor prognosis the data were related to patient survival after 2 years. It was found that the standard cut off values, obtained from the upper limits of normal, healthy subjects, were sensitive but had low specificity. A better relation to prognosis was usually found at a higher discrimination limit. The degree of elevation appears more important than the elevation of the markers as such in indicating a poor prognosis. By systematic adjustment of the discrimination levels, higher specificity can be obtained with little loss of sensitivity.

Topics: Acid Phosphatase; Antigens, Neoplasm; Antigens, Surface; Antigens, Tumor-Associated, Carbohydrate; Biomarkers, Tumor; Biopterins; Calcium-Binding Proteins; Humans; Male; Neopterin; Osteocalcin; Peptides; Prostatic Neoplasms; Reference Values; Tissue Polypeptide Antigen; Vitamin K

Fifty-four subjects were studied: 36 advanced prostatic adenocarcinoma patients in stage D and 18 normal age-matched male controls. Serum alkaline phosphatase, serum acid phosphatase, plasma osteocalcin, 24-h urinary hydroxyproline excretion, and 24-h whole-body retention of [99mTc]-methylene diphosphonate were measured in all subjects before and 3, 6, and 9 weeks after the start of treatment. Skeletal metastases were identified by radiography and/or [99mTc]-methylene diphosphonate bone scan. The results confirm that acid phosphatase is a significant marker in prostatic cancer; serum alkaline phosphatase may be useful in the evaluation and monitoring of bone metastases but it is not always specific; urinary excretion of hydroxyproline is an index of osteoclastic activity; serum osteocalcin may be considered more specific in the evaluation and monitoring of osteoblastic bone metastases in prostatic cancer.

Topics: 1-Carboxyglutamic Acid; Acid Phosphatase; Aged; Aged, 80 and over; Alkaline Phosphatase; Biomarkers, Tumor; Bone and Bones; Bone Neoplasms; Calcium-Binding Proteins; Humans; Hydroxyproline; Male; Middle Aged; Neoplasms, Hormone-Dependent; Osteocalcin; Prostatic Neoplasms; Radionuclide Imaging; Vitamin K

In 62 patients with histologically confirmed carcinoma of the prostate bone scintigraphy, radiographic survey and serum prostatic acid phosphatase determinations were carried out to evaluate the progression of the disease and to compare the relative sensitivity of the diagnostic tools. Thirty-five patients had scintigraphic evidence of skeletal metastases, whereas abnormal X-ray survey and elevated prostatic acid phosphatase levels were found in only 4 and 19 patients, respectively, all of whom had positive scintigraphic findings. Radiographic evidence of metastases was not found in any of the patients with normal scintigraphy, while elevated prostatic acid phosphatase was found in two patients. It is concluded that bone scintigraphy is far more sensitive than either radiographic survey or determination of prostatic acid phosphatases in the diagnosis of skeletal involvement in prostatic carcinoma, and should be the method of choice for this purpose.

Topics: Acid Phosphatase; Bone Neoplasms; Carcinoma; Clinical Enzyme Tests; Humans; Male; Prostate; Prostatic Neoplasms; Radiography; Radionuclide Imaging; Sensitivity and Specificity

Sixty-seven previously untreated patients presenting with clinical stage C prostatic carcinoma with no evidence of distant metastases received combination therapy using the antiandrogen Flutamide and the LHRH agonist [D-Trp6]LHRH ethylamide for an average duration of treatment of 23.5 months. Only five patients have so far shown treatment failure with 91.8% of the patients still in remission at 2 years. Three patients have died from prostate cancer while three have died from other causes, 93.5% of the patients being alive at 2 years. Local control was achieved rapidly in all except one patient. Urinary obstruction and hydronephrosis were corrected in all cases. When comparing to recent data obtained after single endocrine therapy (orchiectomy or estrogens), or radiotherapy, the rate of treatment failure at 2 years is 3.5-fold lower after combination therapy (8.2%) than monotherapy (28.4%). The death rate at 2 years following start of the combination therapy is 6.5% while it is on average 22.2% (3.4-fold higher) in the studies using monotherapy (orchiectomy or estrogens) or radiotherapy. The present data suggest that treatment of prostate cancer with combination therapy before clinical evidence of dissemination of the disease permits a better response which is possibly explained, at least in part, by the lower degree of dedifferentiation and heterogeneity of the tumors.

Topics: Acid Phosphatase; Adenocarcinoma; Adrenal Cortex Hormones; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Delayed-Action Preparations; Flutamide; Gonadotropin-Releasing Hormone; Gonadotropins, Pituitary; Humans; Male; Middle Aged; Neoplasm Staging; Prostatic Neoplasms; Testosterone; Triptorelin Pamoate

The daily variation of serum levels of prostatic acid phosphatase (PAP) determined by the Roy enzymatic method was investigated in 10 patients with metastatic prostatic cancer and in 10 patients without prostatic disease. Duplicate serum samples were obtained from all patients on the same day at 8 AM, 12 PM, 4 PM, and 8 PM. Statistical analysis of the mean PAP levels at the four sampling times in both groups of patients demonstrated no evidence of circadian or diurnal rhythmic variation. Prostate cancer patients did show significantly greater variability in daily PAP than patients without prostatic disease, although a distinct pattern of secretion was not observed in either group. These results underscore the potential inaccuracy of the use of single determination of serum PAP as a parameter of response in patients with metastatic prostatic cancer and in the staging of patients with clinically localized prostatic malignancy. Evaluation of trends of PAP levels over time, however, continues to play a major role in the assessment and management of patients with prostatic carcinoma.

Topics: Acid Phosphatase; Adult; Aged; Bone Neoplasms; Carcinoma; Circadian Rhythm; Humans; Male; Prostate; Prostatic Neoplasms

Since 1981 we have been studying prostate cancer (Pca) by mass screening in three cities, eight towns and seven villages in Gunma prefecture, Japan. From 1981 to 1985, 5,770 subjects were examined. The clinical character of Pca detected by mass screening is compared with control (i.e., Pca detected in the outpatient clinic in Gunma University). Of the 54 Pca patients detected by mass screening (Stage B: 28, C: 8, D: 18), approximately 50% had early-stage Pca. The ratio of early-stage Pca is significantly higher than in the control. An extended survival rate in high-stage Pca detected by mass screening also was observed through comparison with control. We determined two types of Pca in advanced stage: (1) asymptomatic or less symptomatic and better prognostic Pca found in mass screening and (2) symptomatic and worse prognostic Pca found in control.

Topics: Acid Phosphatase; Aged; Aged, 80 and over; Biopsy; Gait; Humans; Japan; Male; Mass Screening; Middle Aged; Pain; Palpation; Prognosis; Prostatic Neoplasms; Surveys and Questionnaires; Urination Disorders

Eleven previously untreated patients with stage D prostate cancer were treated with ketoconazole in a dosage of 400 mg p.o. every 8 h. s-Testosterone was used as a measure of antiandrogen effect. Nine patients had a reduction in s-testosterone to castrate levels (less than 2.9 nmol/l) within 3 days. In the remaining two patients, dose escalation of ketoconazole to 400 mg every 6 h did not lead to sufficient reduction in s-testosterone. Two patients had a complete response and four patients had a partial response of 6/11. Additionally, two patients had bone pain relief without normalization of acid phosphatase. Side-effects and adverse reactions were prominent, causing discontinuation of the treatment in nine patients. It is concluded that high-dose ketoconazole is effective in disseminated prostate cancer, but the high frequency of side-effects makes it less attractive than conventional hormone manipulations like castration or estrogens.

Topics: Acid Phosphatase; Adult; Aged; Humans; Hydrocortisone; Ketoconazole; Male; Middle Aged; Prostatic Neoplasms; Testosterone; Tomography, X-Ray Computed

Topics: Acid Phosphatase; Adult; Aged; Aged, 80 and over; Alkaline Phosphatase; Bone and Bones; Bone Neoplasms; Clinical Enzyme Tests; Humans; Male; Middle Aged; Predictive Value of Tests; Prostate; Prostatic Neoplasms; Radionuclide Imaging

Topics: Acid Phosphatase; Biomarkers, Tumor; Humans; Male; Neoplasm Staging; Prostatic Neoplasms; Prostatic Secretory Proteins; Proteins; Seminal Plasma Proteins

To evaluate the histogenesis of small cell carcinoma of the prostate, 18 cases of this tumor (9 pure small cell and 9 combined adeno- and small cell carcinoma) were studied using immunohistochemical methods. Seven of the small cell components also were assessed by electron microscopic examination. Using neuron-specific enolase (NSE), prostatic acid phosphatase (PAP), and prostate-specific antigen (PSA) on tissue sections, three distinctive immunostaining patterns of small cell carcinoma components were identified: staining positive for NSE and negative for PSA and PAP (10 cases), staining positive for PSA and PAP and negative for NSE (3 cases), and negative reaction for all three antigens (5 cases). Electron microscopic study demonstrated neurosecretory granules in two cases. Based on the immunostaining and electron microscopic findings, small cell carcinomas of the prostate appear to be a heterogeneous group of tumors. Some of them are neuroendocrine carcinomas whereas others are poorly differentiated adenocarcinomas or, possibly, reserve cell carcinomas. Differences in immunostaining patterns or presence and absence of adenocarcinoma component do not reflect any differences in the uniformly poor prognosis of small cell carcinomas, in which median survivals is 7.7 months. The authors believe that, because of such heterogeneity, small cell carcinomas of the prostate arise from multipotential prostatic epithelium and that an origin from specific neuroendocrine cells need not be implicated.

Topics: Acid Phosphatase; Adenocarcinoma; Antigens; Carcinoma, Small Cell; Histocytochemistry; Humans; Immunosorbent Techniques; Male; Microscopy, Electron; Phosphopyruvate Hydratase; Prostate-Specific Antigen; Prostatic Neoplasms

Prostate specific antigen, prostatic acid phosphatase antigen and acid phosphatase activity were measured on 175 serum samples serially collected from 80 patients with metastatic stage D adenocarcinoma of the prostate. Prostate specific antigen and prostatic acid phosphatase antigen concentrations were measured with a monoclonal radioimmunometric assay, and acid phosphatase activity was measured enzymatically. The over-all frequency of abnormal levels of prostate specific antigen (76 per cent) was significantly greater than abnormal prostatic acid phosphatase antigen (60 per cent) and acid phosphatase activity (49 per cent) results (p less than 0.001). These differences were greater among the subset of patients in clinical remission. Levels greater than 10 times normal were observed in 68 per cent of prostate specific antigen, 43 per cent of prostatic acid phosphatase antigen and 31 per cent of acid phosphatase activity measurements (p less than 0.001). Three or more serial prostate specific antigen measurements in 17 patients demonstrated excellent correlation with independently assessed clinical disease activity. These results suggest that prostate specific antigen is a more sensitive and potentially more useful tumor marker than acid phosphatase measurements in patients with metastatic prostatic carcinoma.

Topics: Acid Phosphatase; Adenocarcinoma; Adult; Antigens; Humans; Male; Neoplasm Metastasis; Prospective Studies; Prostate-Specific Antigen; Prostatic Neoplasms; Radioimmunoassay

Fifty carcinomas that were partially to completely papillary in nature were examined. According to urethroscopic and rectal palpation findings, six of the carcinomas were located centrally, 40 tumors were in the prostate proper, and four were clinical stage T0. The epithelium of the papillary portions of the tumors was dark in some instances, light in others. Immunohistochemistry revealed that 20 of 22 tumors were positive for prostatic acid phosphatase (PAP) and prostate-specific antigen (PSA). In no case was a topical relationship to the utriculus prostaticus demonstrable. The epithelium of the utriculus in seven additional patients who were not involved in this series also stained positively for PAP and PSA. Usual carcinomas of the prostate proper can develop endometrioid structures that do not differ immunohistochemically from ordinary portions of the carcinoma. Tumors located in central portions of the prostate are, in our opinion, morphologic variants of usual prostatic carcinomas, and apparently arise in prostatic ducts. We conclude that a distinction between endometrioid carcinomas and tumors of prostatic ducts does not seem justified and that papillary prostatic carcinomas should be treated like common prostatic cancer.

Topics: Acid Phosphatase; Adenocarcinoma; Age Factors; Antigens; Carcinoma, Papillary; Histocytochemistry; Humans; Male; Middle Aged; Neoplasm Invasiveness; Prostate-Specific Antigen; Prostatic Neoplasms

A comparative study was done of the usefulness of immunohistochemical stains for prostate specific antigen and prostatic acid phosphatase in 20 poorly differentiated prostatic tumors. The stain for prostatic acid phosphatase was preferable to the prostate specific antigen stain not only because it was more intense and, therefore, more visible but also because it often was positive in areas in which an equivocal or negative stain was obtained with prostate specific antigen.

Topics: Acid Phosphatase; Antigens; Antigens, Neoplasm; Humans; Immunoenzyme Techniques; Male; Prostate-Specific Antigen; Prostatic Neoplasms; Staining and Labeling

We analyzed serum and bone marrow levels of prostatic specific antigen and prostatic acid phosphatase quantified by double antibody radioimmunoassay in 70 patients. Of the patients 36 had prostatic cancer, including 23 with metastatic disease. There was a significant correlation between the serum and bone marrow levels of prostatic specific antigen and prostatic acid phosphatase independently of the metastases (p less than 0.001). No patient with prostatic cancer and positive bone marrow prostatic specific antigen or prostatic acid phosphatase levels had normal serum levels. Quantification of bone marrow prostatic specific antigen and prostatic acid phosphatase does not provide more information than does serum determination.

Topics: Acid Phosphatase; Aged; Aged, 80 and over; Antigens; Antigens, Neoplasm; Bone Marrow; Humans; Male; Middle Aged; Prognosis; Prostate-Specific Antigen; Prostatic Neoplasms; Radioimmunoassay

A rare case of urethral metastasis from prostatic adenocarcinoma is reported. Ordinary histological examination by hematoxylin and eosin staining could not determine whether the primary site was the prostate or the urethra. However, with an immunoperoxidase technique using prostate-specific acid phosphatase and prostate-specific antigen as markers for prostatic cells, we obtained a precise diagnosis of the primary sites. As a result, the patient could be successfully treated with hormonal therapy.

Topics: Acid Phosphatase; Adenocarcinoma; Aged; Antigens; Antigens, Neoplasm; Humans; Immunoenzyme Techniques; Male; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Urethral Neoplasms

We have studied the mode of excretion of three prostatic secretory proteins, namely acid phosphatase (PAP), prostate-specific antigen (PSA) and beta-inhibin, in the urine of normal adult men, and we have determined the urinary levels of these proteins in men with benign prostatic hypertrophy (BPH) or adenocarcinoma. The output of the three proteins was highly variable during the day. In order to minimize these variations, 24-hour urine samples were collected thereafter. Our study showed that PAP concentrations in 50% of men with or without symptomatic BPH were similar to those of normal young men. In the remaining 50%, PAP was undetectable. In contrast, average PSA and beta-inhibin concentrations were higher in patients with BPH than in young men (p less than 0.05). The three markers were decreased or nondetectable in about half of the patients with untreated prostatic cancer. This phenomenon was even more pronounced in patients receiving hormonal treatment (castration or diethylstilbestrol). However, some of these patients still excreted normal amounts of PAP, PSA, and beta-inhibin. Urinary and serum PAP levels showed no correlation. These results indicate that urinary prostatic markers provide an easy means to study the behavior of the primary prostatic tumor. This information may be of potential value since it is not obtained with serum markers which originate mostly from metastatic cells.

Topics: Acid Phosphatase; Adenocarcinoma; Adult; Antigens; Antigens, Neoplasm; Humans; Male; Peptides; Prostate-Specific Antigen; Prostatic Hyperplasia; Prostatic Neoplasms; Prostatic Secretory Proteins

To recognize progression of an inoperable prostatic cancer we use clinical parameters and the prostate specific phosphatase. The prostate specific antigen (PSA) is a new, sensitive and specific laboratory tumor marker. With 363 specimens of patients without prostatic cancer we defined for the normal range of this serum parameter. In 98 men with histologically proven prostatic cancers we investigated for the clinical relevancy of the serum level of PSA. We believe, that measurement of serum PSA give important information for clinical management of prostatic cancer.

Topics: Acid Phosphatase; Adolescent; Adult; Aged; Aged, 80 and over; Antigens; Diagnosis, Differential; Follow-Up Studies; Humans; Male; Middle Aged; Prostate; Prostate-Specific Antigen; Prostatic Hyperplasia; Prostatic Neoplasms; Radioimmunoassay

Topics: Acid Phosphatase; Antigens; Humans; Male; Prostate-Specific Antigen; Prostatic Neoplasms; Radioimmunoassay

A study was performed on 130 men to compare the level of serum prostate-specific antigen (PSA) in controls, patients with benign prostatic hyperplasia (BPH) and patients with prostatic carcinoma. The results showed that all 30 normal controls below 40 years of age had values less than 10 ng/ml. Of the 40 patients with BPH, all aged over 40 years, 13 (32.5%) had raised levels above 10 ng/ml. In the 60 patients with prostatic carcinoma, all over 40 years, 24 had localised disease (MO) and 36 had metastatic spread (M1), as judged by isotope bone scan. In patients with MO disease, 16 (66.6%) had raised PSA levels compared with 34 (94.5%) of those with M1 disease. The corresponding figures for raised prostatic acid phosphatase (PAP) values were 4% in the MO group and 52.7% in the M1 group. PSA levels reflected neither the histological grade nor the local stage of the tumour and were of no value in estimating tumour burden. PSA was found to be a valuable index in the management of prostatic cancer because of this sensitivity. Stable disease not requiring hormonal manipulation was reflected by unchanging levels of PSA, whereas progressive disease requiring hormonal therapy was reflected by an alteration in the PSA levels corresponding to the patients' response. The same group of progressive disease patients showed only a 50% rise in serum PAP levels, confirming the greater sensitivity of PSA as a measure of prostate cancer. PSA measurements should be included in any further trials on prostatic carcinoma and should be regarded as a standard marker for evaluating response to therapy.

Topics: Acid Phosphatase; Adult; Aged; Aged, 80 and over; Antigens; Antigens, Neoplasm; Humans; Male; Middle Aged; Prostate-Specific Antigen; Prostatic Hyperplasia; Prostatic Neoplasms

To compare the clinical usefulness of the serum markers prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP), we measured them by radioimmunoassay in 2200 serum samples from 699 patients, 378 of whom had prostatic cancer. PSA was elevated in 122 of 127 patients with newly diagnosed, untreated prostatic cancer, including 7 of 12 patients with unsuspected early disease and all of 115 with more advanced disease. The PSA level increased with advancing clinical stage and was proportional to the estimated volume of the tumor. The PAP concentration was elevated in only 57 of the patients with cancer and correlated less closely with tumor volume. PSA was increased in 86 percent and PAP in 14 percent of the patients with benign prostatic hyperplasia. After radical prostatectomy for cancer, PSA routinely fell to undetectable levels, with a half-life of 2.2 days. If initially elevated, PAP fell to normal levels within 24 hours but always remained detectable. In six patients followed postoperatively by means of repeated measurements, PSA--but not PAP--appeared to be useful in detecting residual and early recurrence of tumor and in monitoring responses to radiation therapy. Prostate massage increased the levels of both PSA and PAP approximately 1.5 to 2 times. Needle biopsy and transurethral resection increased both considerably. We conclude that PSA is more sensitive than PAP in the detection of prostatic cancer and will probably be more useful in monitoring responses and recurrence after therapy. However, since both PSA and PAP may be elevated in benign prostatic hyperplasia, neither marker is specific.

Topics: Acid Phosphatase; Adenocarcinoma; Adult; Aged; Antigens; Antigens, Neoplasm; Biopsy; Half-Life; Humans; Male; Middle Aged; Monitoring, Physiologic; Neoplasm Recurrence, Local; Prostate; Prostate-Specific Antigen; Prostatectomy; Prostatic Hyperplasia; Prostatic Neoplasms

Dunning R3327-H rat prostate adenocarcinoma cells, when grown in syngeneic (Copenhagen) rats or nude mice, produce tumors with prominent hypercellular stroma. The authors have previously demonstrated the presence of anomalous steroid-sensitive cells in both the epithelium and stromal compartments of this model system. In order to better understand the histogenesis of these cells, the authors studied samples of the tumor which were radiolabeled overnight with tritiated dihydrotestosterone (3H-DHT). Frozen sections of the tissues were thaw-mounted onto autoradiographic emulsion-coated slides to permit silver grain identification in association with nuclei of androgen-sensitive cells. Surprisingly, numerous silver grains were found to be associated with nuclei of large cells within the stroma. Therefore, these cells were termed "epithelioid" pending confirmation of their origin. To further define these cells and their relationship to the surrounding matrix, autoradiograms have now been examined immunohistochemically with antibodies directed against the basement membrane glycoprotein, laminin, as well as antibodies specific for intermediate cytoskeletal filaments. Following identification of acinar basement membranes, epithelioid cells were identifiable both in the stroma and in the acinar epithelial cell layer. Histochemical staining with acid phosphatase, a marker for prostatic epithelium, was performed and shown to be present in acinar epithelial cells as well as in epithelioid cells. Additionally, fluorescence-activated cell sorting was employed to characterize the DNA content of cell types within the H tumor. Epithelioid cells were found to be in highest concentration in an aneuploid peak with a ploidy of approximately 6N. The autoradiographic, immunohistochemical, cytometric, and ultramicroscopic studies suggest that 1) epithelioid cells are epithelial derived stromal cells; 2) these epithelioid cells arise by pathologic division of aneuploid neoplastic precursor cells of approximately 3N ploidy, which are found within the prostatic epithelium; and 3) the resulting 6N cells degrade the basement membrane locally, invade the stroma, and populate it. Here, they can be distinguished from fibroblasts by their size, acid phosphatase activity, and hormone receptor content. Thus, the term "epithelioid" is inappropriate; and these cells should be regarded simply as large neoplastic epithelial (LNE) cells. The presence of this cell type suggests that this tumor s

Topics: Acid Phosphatase; Adenocarcinoma; Animals; Autoradiography; Cell Nucleus; Cell Separation; Cytoplasm; Dihydrotestosterone; Epithelium; Flow Cytometry; Histocytochemistry; Immunoenzyme Techniques; Keratins; Male; Mice; Mice, Nude; Prostatic Neoplasms; Rats; Tritium

Topics: Acid Phosphatase; Antigens, Neoplasm; Humans; Immunohistochemistry; Male; Neoplasm Metastasis; Prostate-Specific Antigen; Prostatic Neoplasms

In an effort to determine which of five tests was the most efficient in the diagnosis of prostate cancer, 280 male patients were screened employing aspiration cytology, transrectal ultrasound, acid phosphatase, prostate specific antigen, and the digital rectal examination. The digital rectal examination was the most efficient (75%) and in order of decreasing accuracy were prostate specific antigen (74%), prostatic ultrasound (71%), acid phosphatase (66%), and finally aspiration cytology (63%). In an era when what are more expensive and more technology are assumed to be better, what is simple and traditional is ignored. From an evaluation of these patients it appears that the digital rectal examination still retains its diagnostic efficiency. Finally, in this age of escalating medical costs and physician accountability for these expenses, you can't beat the cost - benefit ratio for the old fashioned rectal exam.

Topics: Acid Phosphatase; Aged; Antigens, Neoplasm; Humans; Male; Prostate-Specific Antigen; Prostatic Hyperplasia; Prostatic Neoplasms; Rectum; Ultrasonography

Serum prostatic specific antigen and prostatic acid phosphatase levels were measured retrospectively and evaluated in 357 men with benign prostatic hypertrophy and in 209 men with various stages of prostatic carcinoma. Although prostatic specific antigen values were elevated in 21 per cent of the patients with benign prostatic hypertrophy, the elevations usually were low and did not interfere with clinical interpretation. Prostatic specific antigen was elevated in 98 per cent of 86 men with active stage D2 disease; in 22 per cent of the men prostatic specific antigen was the only elevated marker. In contrast, prostatic acid phosphatase was the only elevated marker in 1 per cent of the patients with stage D2 disease and neither marker was elevated in 2 per cent. Among 74 patients in whom prostatic specific antigen and prostatic acid phosphatase determinations were made before radical prostatectomy, prostatic specific antigen was elevated substantially (greater than 10 ng. per ml.) in 59 per cent (26 of 44) with extracapsular disease and in only 7 per cent (2 of 30) without extracapsular disease. More importantly, of those 28 patients with substantially elevated prostatic specific antigen levels 26 (93 per cent) had extracapsular disease. Serial serum measurements showed that prostatic specific antigen either reflected or predicted clinical status in more than 97 per cent of the patients. We conclude that prostatic specific antigen is an excellent serum tumor marker for monitoring patients with prostatic carcinoma and that it surpasses prostatic acid phosphatase in this regard. Prostatic specific antigen also may be useful in staging prostatic carcinoma and it may change our attitudes significantly about the therapeutic responses to this cancer.

Topics: Acid Phosphatase; Antigens, Neoplasm; Biomarkers, Tumor; Clinical Enzyme Tests; Epitopes; Humans; Male; Monitoring, Physiologic; Neoplasm Staging; Prognosis; Prostate; Prostate-Specific Antigen; Prostatic Hyperplasia; Prostatic Neoplasms; Retrospective Studies

Combined measurement of serum prostate-specific antigen (PA) and prostatic acid phosphatase (PAP) was performed in 235 patients with various urologic diseases including 55 patients with prostatic cancer. A PA level of over 24.7 ng/ml and a PAP level of over 3.1 ng/ml were considered to be positive. The positive rate of PA was 57% in the patients with untreated prostatic cancer and 3% in the patients without prostatic cancer. The positive rate of PAP was 52% in the patients with untreated prostatic cancer and 1% in the patients without prostatic cancer. PA and PAP were considered to be equally sensitive and specific serum markers of prostatic cancer. However, the positive rate increased to 65% without increasing the false positive rate when the PA and PAP were both measured simultaneously. The combined assay of PA and PAP is recommended for screening prostatic cancer. The cross-over titer of PA and gamma-Sm using standard samples in each kit revealed linearity, which suggested that PA and gamma-Sm possess the same antigenicity.

Topics: Acid Phosphatase; Aged; Antigens, Neoplasm; Biomarkers, Tumor; Humans; Male; Middle Aged; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Prostatic Secretory Proteins; Proteins; Radioimmunoassay; Seminal Plasma Proteins

Clinical and laboratory studies have confirmed the efficacy of alpha-fetoprotein (AFP) and human chorionic gonadotropin (hCH) as tumor markers in the diagnosis, monitoring and assessment of prognosis in cases of testicular tumor. Serum AFP level is positive in 75% of yolk sac tumors, 70% of embryonal carcinomas and 62% of teratomas. All cases of choriocarcinoma show elevated serum hCG. In the treatment of prostatic cancer, prostatic acid phosphatase (PAP), prostatic-specific antigen (PA) and gamma-seminoprotein (gamma-Sm) are important serum markers, and the RIA method has improved their specificity and sensitivity. These markers are also correlated well with therapeutic efficacy. Especially, improvement of the serum PAP level in patients with stage C and D cancer indicates prolongation of survival time. Over 90% of the metastatic lesions of prostatic cancer are encountered in the skeletal system. Thus, serum alkaline phosphatase and urinary hydroxyproline are considered to be useful markers for indicating bone involvement. In other urological malignancies, there are no specific tumor markers. As non-specific markers for renal cell carcinoma, ESR, LDH, CEA, alpha 2-globulin, haptoglobin, fibrinogen and various hormones have been investigated. In the treatment of bladder cancer, it is important to distinguish the malignant potential of the tumor. From this viewpoint, various immunohistochemical investigations and flow cytometric analysis are now in progress. It is expected that some of the findings of the studies could prove to be of clinical use in the near future.

Topics: Acid Phosphatase; alpha-Fetoproteins; Biomarkers, Tumor; Chorionic Gonadotropin; Humans; Kidney Neoplasms; Male; Prognosis; Prostatic Neoplasms; Urinary Bladder Neoplasms; Urogenital Neoplasms

We did a comparative analysis of the physiological and analytical properties of prostate-specific antigen (PSA), acid phosphatase (ACP; EC 3.1.32) activity, and acid phosphatase antigen (PAP) in serum. The PSA assay is sensitive to 0.2 microgram/L and demonstrates good linearity (y = 1.01x + 0.74). The CV was 3.9% at 40 micrograms/L, 8.0% at 3.1 micrograms/L. PSA and PAP are less stable at 4 degrees C than at -20 degrees C. Serum PAP and ACP concentrations showed large intra-individual fluctuations (average CVs of 22% and 24%, respectively), which were not observed with PSA measurements (average CV 6.2%). We saw significant correlation with the magnitude of physiological change when analytes were compared for serially collected split samples [y(PSA) = 0.14x(PAP) + 0.00, r = 0.767], which indicates that a common factor is influencing this variation. The excellent analytical performance, tissue specificity, and small degree of intra-individual variance are characteristics that favor the measurement of PSA in serum for monitoring patients with prostatic cancer.

Topics: Acid Phosphatase; Antigens, Neoplasm; Humans; Male; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms

Prostatic specific antigen (PA) level was determined with a Wako test kit (Japan) for prostatic cancer and others. The incidence of abnormal values of PA in untreated prostatic cancer, was 50, 50, 80, and 100% for stage A1, C (pN0, NX), D1 and D2 cancers, respectively. Grade was not related to the level of PA. Prostatic hypertrophy, prostatitis and urinary stone showed a false positive rate of 52, 18 and 0%, respectively. The level of PA was not correlated to those of prostatic acid phosphatase (RIA). In 31% of the cases, the elevated PA decreased 4 weeks after start of endocrine treatment. Elevated PA in low grade cancer was not normalized as much as that in high and moderate grade cancers. The positive rate of PA in the serum of reactivated patients was significantly higher than that of the patients with cancer under good control by endocrine treatment.

Topics: Acid Phosphatase; Antigens, Neoplasm; False Positive Reactions; Humans; Male; Prostate-Specific Antigen; Prostatic Hyperplasia; Prostatic Neoplasms; Prostatitis; Urinary Calculi

We evaluated the analytical performance of a new monoclonal immunoradiometric assay ("M-PSA") for prostate-specific antigen ("Tandem"; Hybritech Inc.) in comparison with a monoclonal immunoradiometric assay ("M-PAP") for mass measurement of prostatic acid phosphatase ("Tandem") and with a conventional enzyme-activity assay ("E-PAP") for prostatic acid phosphatase (EC 3.1.3.2). For M-PSA, the CVs were 1.3-3.0% within-run and 3.0-4.9% between-run. The minimum detectable mass concentration was 0.10 microgram/L, and linearity extended to 100 micrograms/L. The reference interval for M-PSA in 178 healthy men was 0-2.8 micrograms/L. Serum specimens from men with prostatic disease (primarily prostatic carcinoma and benign prostatic hypertrophy) were assayed by the three methods. Correlation was best between mass measurement (M-PAP) and enzyme activity (E-PAP) for prostatic acid phosphatase (r = 0.958). Results for PSA did not correlate well with those for either M-PAP (r = 0.629) or E-PAP (r = 0.387). PSA was increased in a higher percentage of specimens from men with earlier (clinical stage B) prostatic carcinoma than were results from either assay for PAP.

Topics: Acid Phosphatase; Antibodies, Monoclonal; Antigens, Neoplasm; Biomarkers, Tumor; Female; Humans; Male; Prostate-Specific Antigen; Prostatic Hyperplasia; Prostatic Neoplasms

The reactivity of the anti-Leu 7 monoclonal antibody (Leu 7) was tested on 83 human tumours and on non-neoplastic prostatic, hepatic and pancreatic tissues. A four-step peroxidase-anti-peroxidase method was used on paraffin embedded tissues and we observed strong cytoplasmic positivity in all 19 primary prostatic tumours, in two metastatic, poorly differentiated prostatic adenocarcinomas, and in normal and hypertrophic prostatic epithelium. All the primary prostatic tumours also stained positively for prostate-specific antigen and for prostatic acid phosphatase using polyclonal antisera. The degree of positivity for these antigens varied from case to case. Adenocarcinomas arising from the gastrointestinal tract, pancreas and gallbladder were anti-Leu 7 negative. Focal Leu 7 positivity, largely confined to cell membranes, was observed in some ovarian, endometrial, renal, lung and breast adenocarcinomas. These tumours, as well as some of the gastrointestinal, hepatic and pancreatic tumours, also showed focal cytoplasmic positivity for prostate-specific antigen and prostatic acid phosphatase. Our findings suggest that the anti-Leu 7 monoclonal antibody is a marker that may facilitate the detection of metastatic prostatic adenocarcinoma, especially when used in conjunction with staining for prostate-specific antigen.

Topics: Acid Phosphatase; Adenocarcinoma; Antibodies, Monoclonal; Antigens, Differentiation, T-Lymphocyte; Antigens, Neoplasm; Female; Humans; Immunohistochemistry; Male; Prostate-Specific Antigen; Prostatic Neoplasms

A breast mass developed in a patient receiving estrogen therapy for prostatic cancer. The prostate tumor was adenocarcinoma of small acinar type, whereas that of the breast was infiltrating medullary adenocarcinoma. Histological features of the two tumors differed and double cancer was suspected by conventional pathological study. However, immunohistochemical staining with prostatic specific antigen and prostatic acid phosphatase was positive in each tumor. These results indicate the breast tumor to be a metastasis from the prostatic cancer.

Topics: Acid Phosphatase; Adenocarcinoma; Aged; Antigens, Neoplasm; Breast; Breast Neoplasms; Humans; Immunoenzyme Techniques; Male; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms

Topics: Acid Phosphatase; Antigens, Neoplasm; Biomarkers, Tumor; Blood Proteins; Humans; Male; Prostate-Specific Antigen; Prostatic Hyperplasia; Prostatic Neoplasms; Prostatic Secretory Proteins; Seminal Plasma Proteins

A commercially available radioimmunoassay (RIA) for prostate specific antigen (PSA) was investigated in respect to its analytical specificity and its clinical applicability for the diagnosis of prostate cancer. PSA detected in serum by RIA was immunochemically identical to PSA found in seminal plasma. PSA is not a single protein but rather a group of isoproteins with different isoelectric points (pI) in the pH range 6-8. Furthermore PSA could be split in subunits by means of denaturing electrophoresis under reducing conditions. Unlike prostatic acid phosphatase (PAP) serum PSA was stable at room temperature. In sera of patients with benign hyperplasia of the prostate (BPH) two significantly different populations were found. The lower group (0.5-5.8 ng/ml PSA) had PSA values comparable to the control group of apparently healthy males (0.5-6.3 ng/ml). The higher group between 7.7 and 12.2 ng/ml was also characteristic for early stages of prostate cancer (T0 and T1). PSA seemed to be correlated to the tumor volume and allowed to differentiate between early carcinomas of the prostate and BPH or possibly T0/1 staged prostate carcinoma. PSA may be a screening method for early cancer of the prostate.

Topics: Acid Phosphatase; Antigens, Neoplasm; Biomarkers, Tumor; Humans; Isoelectric Focusing; Male; Prostate-Specific Antigen; Prostatic Hyperplasia; Prostatic Neoplasms; Radioimmunoassay; Reagent Kits, Diagnostic; Semen

Serum tissue polypeptide antigen (s-TPA) levels were determined in 124 patients having urogenital carcinomas, 74 with benign urological diseases and 55 normal subjects. We analyzed these results and determined the clinical significance of s-TPA as a tumor marker for urogenital carcinomas. S-TPA levels in the 55 normal subjects was 80 +/- 17 U/L (mean +/- S.D.). Since more than 95% of them showed an s-TPA level of below 110 U/L, this level was used as the cut-off value. The s-TPA level was 125 +/- 75 U/L for the 42 patients with benign prostatic hypertrophy, 138 +/- 60 U/L for the 15 patients with acute urinary tract infections (UTI) and 80 +/- 20 U/L in the 17 patients having other benign urological diseases. An elevated s-TPA level was clearly demonstrated in the case of acute UTI, which displayed a false positive result. The s-TPA level was 207 +/- 246 U/L for the 21 patients with bladder carcinoma, 197 +/- 52 U/L for the 5 patients with renal pelvic or ureteral carcinoma, 187 +/- 156 U/L for the 22 patients with renal cell carcinoma, 167 +/- 183 U/L for the 46 patients with prostatic carcinoma, and 95 +/- 28 U/L for the 8 patients with testicular carcinoma. In the 8 patients having bladder carcinoma, the elevation of s-TPA level seemed to be caused by the concomitant presence of acute UTI. The positive rate of s-TPA in various urogenital carcinomas was 100% for renal pelvic or ureteral carcinoma, 68% for renal cell carcinoma, 59% for bladder carcinoma, 52% for prostatic carcinoma and 13% for testicular carcinoma.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acid Phosphatase; Adolescent; Adult; Aged; Aged, 80 and over; Antigens, Neoplasm; Biomarkers, Tumor; Carcinoma, Renal Cell; Female; Humans; Kidney Neoplasms; Male; Middle Aged; Peptides; Prostate-Specific Antigen; Prostatic Neoplasms; Prostatic Secretory Proteins; Proteins; Seminal Plasma Proteins; Tissue Polypeptide Antigen

We measured the prostatic acid phosphatase (PAP), gamma-Seminoprotein (gamma-Sm) and prostate specific antigen (PA) in the serum of 862 patients with various urologic diseases including 89 patients with prostatic cancer. We used a PAP radioimmunoassay kit, gamma-Sm enzyme immunoassay kit, Markit-F-PA enzyme immunoassay kit and PA test Wako enzyme immunoassay kit. Serum PA level in advanced prostatic carcinoma (stage C, D) tended to be higher than that in early stage cancer (stage A, B). The Wako kit gave a higher PA than the Markit-F in each stage. The sensitivity rate of Wako PA test was the highest (81%) of all kits. The specificity rate of PAP was the highest (83%), and the accuracy rate of Markit-F PA was the highest (79%). The positive rate in the combined assay of PAP, gamma-Sm and PA in prostatic cancer was higher than that in the single assay of each tumor marker. We regarded PAP, gamma-Sm and PA as clinically different tumor markers, because their serum level did not correlate definitely. No apparent correlation was found between histopathological grade and the level of each tumor marker. The level of PAP, gamma-Sm and PA in the reactivated patients was significantly higher than that of the well-controlled patients. In the reactivated patients, the positive rate of Markit-F PA was the highest (89%) of all the kits.

Topics: Acid Phosphatase; Adenocarcinoma; Antigens, Neoplasm; Biomarkers, Tumor; Humans; Male; Neoplasm Staging; Prostate-Specific Antigen; Prostatic Neoplasms; Prostatic Secretory Proteins; Proteins; Seminal Plasma Proteins

Topics: Acid Phosphatase; Adenocarcinoma; Antibodies, Monoclonal; Antigens, Neoplasm; Humans; Immunoenzyme Techniques; Male; Prostate-Specific Antigen; Prostatic Neoplasms

The first xenograft line of small cell undifferentiated carcinoma of the prostate (UCRU-PR-2) has been established and characterized. The donor tumor and the xenograft share the common morphological and ultrastructural features of small cell undifferentiated carcinoma (including neurosecretory granules) but also elaborate epithelial membrane antigen and carcinoembryonic antigen, in addition to neurone-specific enolase. The line expresses a diploid DNA complement. Androgen and estrogen receptors are not expressed, although prostatic acid phosphatase is present in sera from tumor-bearing mice in low levels. From these studies, we postulate a possible common stem cell origin for adenocarcinoma and small cell undifferentiated carcinoma of the prostate; further studies of a cell line derived from this tumor may clarify the issue.

Topics: Acid Phosphatase; Adenocarcinoma; Aged; Animals; Biomarkers, Tumor; Carcinoma, Small Cell; Cell Line; Cells, Cultured; DNA, Neoplasm; Flow Cytometry; Humans; Male; Mice; Mice, Inbred BALB C; Mice, Nude; Neoplasm Transplantation; Prostatic Neoplasms; Receptors, Androgen; Receptors, Estrogen; Transplantation, Heterologous

The clinical and endocrine response to a depot preparation of the LH-RH analogue ICI 118630 (Zoladex) was assessed in 55 untreated patients with advanced prostatic cancer. Whereas gonadal androgen suppression was achieved in all patients, subjective and objective clinical response occurred in only 69%, indicated by a relief of bone pain, a decrease in the size of the primary tumour and lymph node metastases and improvement in bone scan appearances. A third of these patients, however, subsequently showed progression of their disease. Serious side effects were not encountered in this study. The depot formulation is a simple, safe and convenient method of administering Zoladex and offers an alternative treatment for metastatic prostatic cancer.

Topics: Acid Phosphatase; Aged; Alkaline Phosphatase; Bone Neoplasms; Buserelin; Delayed-Action Preparations; Goserelin; Humans; Luteinizing Hormone; Lymphatic Metastasis; Male; Middle Aged; Prospective Studies; Prostatic Neoplasms; Random Allocation; Testosterone

Topics: Acid Phosphatase; Aged; Antineoplastic Agents; Gonadotropin-Releasing Hormone; Humans; Male; Neoplasm Recurrence, Local; Prostatic Neoplasms; Testis; Testosterone; Triptorelin Pamoate

We produced two monoclonal hybridoma cell lines that secrete IgG immunoglobulins with high affinities (Kd = 7.3 to 8.0 X 10(-11) mol/L, Ka = 1.25 to 1.37 X 10(10) L/mol) for 125I-labeled human prostatic acid phosphatase (PAP), and that specifically bind this enzyme from human serum. The antibodies were produced in high titers in murine ascitic fluid (700 mg/L) and in cell-culture media (30 mg/L) and were further purified to homogeneity by affinity chromatography on PAP- and Protein A-Sepharose CL-4B. After purification they were shown to be homogeneous by liquid chromatography. Both of these monoclonal antibodies exhibit strict specificity for PAP as determined by radioimmunoassay and by immunofluorescence studies of human pancreas, kidney, prostate, and leukocytes. The antibodies react only with the native form of the enzyme, as shown by the slot-immunoblotting method.

Topics: Acid Phosphatase; Antibodies, Monoclonal; Antibody Affinity; Antibody Specificity; Chromatography, Affinity; Fluorescent Antibody Technique; Humans; Immunodiffusion; Immunoglobulin G; Male; Prostatic Neoplasms; Radioimmunoassay

The status of patients with skeletal metastases from prostatic carcinoma was determined from a quantitative uptake and retention measurement of the bone scanning radiopharmaceutical 99mtechnetium-methylene diphosphonate. Whole body counts were performed 5 minutes and 24 hours after intravenous administration of 99mtechnetium-methylene diphosphonate, and were expressed as the percentage uptake by the skeleton at 24 hours. Skeletal uptake determinations were done in 29 patients with prostatic cancer (17 with osseous metastases) who were evaluated at 3 to 6-month intervals. Group 1 consisted of patients who responded to therapy and achieved remission, group 2 included patients with relapse or progressive disease, group 3 consisted of those with metastases who were in remission for longer than 6 months and group 4 included those without evidence of any bony metastases. The baseline mean +/- standard deviation 24-hour skeletal uptake values were 46.1 +/- 12.0 per cent in group 1, 34.3 +/- 13.9 per cent in group 2, 27.0 +/- 5.9 per cent in group 3 and 28.9 +/- 5.5 per cent in group 4. At 3 to 6 months the values in group 1 (responders) decreased by 18 per cent, while those in group 2 (relapse or progression) increased by 19 per cent and those in group 3 (remission) increased by 1.5 per cent. The quantitative 24-hour skeletal uptake test was performed easily, reproducible and at least as useful as concurrent chemical blood tests and subjective bone scan interpretations.

Topics: Acid Phosphatase; Alkaline Phosphatase; Bone Neoplasms; Humans; Male; Prostatic Neoplasms; Radionuclide Imaging; Technetium Tc 99m Medronate; Time Factors; Whole-Body Counting

We retrospectively reviewed records of 551 patients with clinical Stage C prostatic adenocarcinoma treated with 60 to 70 Gy external beam radiation. Elective pelvic node irradiation was given to 247 patients (45%). Follow-up for all surviving patients ranged from 16 to 201 months (median, 6.5 years; mean, 7 years). The 5-, 10-, and 15-year uncorrected actuarial survival rates were 72%, 47%, and 27%, respectively. Disease-free survival rates were 59%, 46%, and 40% at the corresponding times. Actuarial local control rates were 88%, 81%, and 75% at 5, 10, and 15 years, respectively. Disease-free survival was adversely affected by high pathologic grade, disease fixed to the pelvic sidewall, invasion of the bladder, prior transurethral resection, hydronephrosis, and elevated serum levels of prostatic acid phosphatase and creatinine. Elective pelvic node irradiation did not improve the outcome. Complications of treatment were acceptable: minor anorectal and/or urinary symptoms, 11%; mild to moderate complications, 19%; serious problems requiring surgery, 3%. It is concluded that localized, high-energy external beam irradiation provides excellent local control of disease, low morbidity, and 5-, 10-, and 15-year survival rates that have not been rivaled by other treatment.

Topics: Acid Phosphatase; Adenocarcinoma; Aged; Creatinine; Cystitis; Hematuria; Humans; Male; Middle Aged; Neoplasm Metastasis; Pelvic Neoplasms; Proctitis; Prognosis; Prostatic Neoplasms; Radiotherapy, High-Energy; Retrospective Studies; Urination

The authors' 5-year experience in the management and care of prostatic carcinoma are summarized. Their method differs essentially from earlier practice. They have found a new diagnostic and therapeutic method by introducing the TECO irradiation therapy, extensively using bone scintigraphy, by introducing cytostatics, extensively applying the prostate-specific acid phosphatase and by performing rectal biopsy of the prostate. They describe their own observations on the diagnostics and therapy of prostatic carcinoma. They stress that none of the therapies is the method of choice, the use of the various kinds of treatment are defined by strict indications. They state that care of prostatic cancer patients is highly important because only observation of the course of the disease may ensure the evaluation of treatment results and the indication of the adequate therapeutic method.

Topics: Acid Phosphatase; Adenocarcinoma; Biopsy; Bone Neoplasms; Carcinoma; Hormones; Humans; Male; Prostate; Prostatectomy; Prostatic Neoplasms; Radionuclide Imaging; Radiotherapy, High-Energy

Topics: Acid Phosphatase; Aged; Humans; Immunoenzyme Techniques; Male; Prostatic Neoplasms

Although chronic treatment with luteinizing hormone-releasing hormone agonists achieves castration levels without side effects other than those related to hypoandrogenism, a limitation to their use alone for the treatment of prostatic cancer is the transient increase in serum androgens that lasts for 5 to 8 days at the start of treatment with the risk of disease flare. Our data show that the concomitant administration of the pure antiandrogen flutamide in association with the luteinizing hormone-releasing hormone agonist (D-Trp6) luteinizing hormone-releasing hormone ethylamide caused a 64 to 78 per cent decrease in serum prostatic acid phosphatase on days 3 and 7 after the start of treatment in 70 patients with previously untreated stage D2 prostatic cancer. Pain, which was present in 41 patients at the start of treatment, did not increase in any patient, it decreased in 7 at 1 week and it disappeared or decreased in 27 at 2 weeks. Performance, which originally was abnormal in 34 patients, became normal in 7 within 1 week and in 20 within 1 month (59 per cent). These data show that the addition of flutamide completely eliminates the risks of disease flare associated with the use of the otherwise exceptionally well tolerated luteinizing hormone-releasing hormone agonists in patients treated for prostatic cancer.

Topics: Acid Phosphatase; Aged; Anilides; Drug Therapy, Combination; Flutamide; Gonadotropin-Releasing Hormone; Humans; Luteinizing Hormone; Male; Prostatic Neoplasms; Testosterone; Triptorelin Pamoate

Five patients who were candidates for radical prostatectomy were investigated. One milligram of diethylene triamine pentaacetic acid derivatives of purified F(ab')2 fragments of monoclonal antibodies against prostatic acid phosphatase, labeled with 99mTc, were bilaterally injected into the periprostatic space. The amount of radioactivity injected varied between 3 and 7 mCi. Imaging took place dynamically for the first hour following injection, then at 6 and 24 hr. In one patient, lymph node metastases were detected in the left paraaortic, iliac, and obturator lymph nodes by this technique. The lesions incorporating radioactivity were confirmed to be metastases of prostatic cancer following staging pelvic lymphadenectomy. Immunolabeling electron microscopy studies revealed internalized antibody in prostatic cancer cells. In the four other patients, radioimaging did not show any lymph node metastases, and this negative finding was confirmed at surgery. These early data indicate the possibility of preoperative staging of prostatic cancer using radiolabeled derivatives of monoclonal antibodies raised against prostatic acid phosphatase and injected into the periprostatic area.

Topics: Acid Phosphatase; Antibodies, Monoclonal; Humans; Immunoglobulin Fab Fragments; Indium Radioisotopes; Lymph Node Excision; Lymph Nodes; Lymphatic Metastasis; Male; Neoplasm Staging; Organometallic Compounds; Pentetic Acid; Prostatic Neoplasms; Radionuclide Imaging; Technetium Tc 99m Pentetate

Topics: Acid Phosphatase; Humans; Immunoenzyme Techniques; Male; Mass Screening; Prostate; Prostatic Neoplasms

The clinical application of enzyme immunoassay (EIA) for prostatic acid phosphatase (PAP) is reported. PAP concentration was measured by an IQ(Bio)PAP-AELIA kit. Serum samples were collected from 20 healthy individuals, 31 patients with benign prostatic hypertrophy, 14 patients with prostatis, 23 patients (47 samples) with prostatic cancer and 29 patients with various other malignancies. The coefficients of variation (%CV) in intraassay and interassay ranged from 2.3 to 4.4%, and from 3.0 to 3.6%, respectively. The recovery rate in the dilution test and recovery test were 106.2 +/- 8.9% and 101.3 +/- 6.9% respectively. A significant correlation (r = 0.994, p less than 0.01) was observed between EIA and RIA methods in the prostatic cancer patients. PAP concentration was elevated above 2.0 ng/ml in 0/2 (0%) of the treated patients with stage B prostatic cancer, 1/5 (20%) of those with stage C, 6/16 (38%) of those with stage D, and in 4/5 (80%) of the untreated patients with stage D prostatic cancer. False positive results were seen in 2/31 (6%) of the patients with benign prostatic hypertrophy, 3/14 (21%) with prostatis and 3/29 (10%) of the patients with various other malignancies. In the majority of the false positive cases, elevated levels were only just above the normal value. In conclusion, the PAP level measured by this EIA kit was correlated with the clinical response to hormone therapy for prostatic cancer.

Topics: Acid Phosphatase; Evaluation Studies as Topic; Female; Humans; Immunoenzyme Techniques; Male; Prostatic Neoplasms; Reagent Kits, Diagnostic

Serum gamma-seminoprotein (gamma-Sm) in patients with prostatic disease was determined by enzyme immunoassay. A total of 136 patients including 13 untreated and 40 treated patients with prostatic cancer, 45 patients with benign prostatic hyperplasia (BPH) and 38 patients with other urological diseases were analyzed. The mean +/- SD of serum gamma-Sm in the 13 patients with untreated prostatic cancer and the 45 patients with BPH was 31.7 +/- 46.1 and 3.7 +/- 6.6 ng/ml, respectively, there being a statistically significant difference between the two groups. All patients with untreated stage A or B prostatic cancer had a serum gamma-Sm of less than 4 ng/ml (cut off value). The mean level of serum gamma-Sm was 5.1 +/- 1.9 ng/ml for all patients with untreated stage C prostatic cancer; 66% of them had a value above the cut off value. However, it was 55.9 +/- 52.6 ng/ml in all patients with untreated stage D prostatic cancer; 87.5% of them had a value above the cut-off value. These results suggest that gamma-Sm may be a useful tumor marker in the management of patients with prostatic cancer.

Topics: Acid Phosphatase; Biomarkers, Tumor; Humans; Immunoenzyme Techniques; Male; Prostatic Neoplasms; Prostatic Secretory Proteins; Proteins; Seminal Plasma Proteins

Effect of chemotherapy for relapse of prostatic cancer was evaluated with new response criteria, in which four objective parameters including the prostate, bone metastasis, soft tissue metastasis and the serum acid phosphatase level estimated by radioimmunoassay or enzyme immunoassay were judged separately and then summarized to evaluate the response as complete response (CR), partial response (PR), stable and progressive disease (PD). Eighty-two patients were included in the study. Rate of PR and stable were 19% and 27%, respectively, and these two groups showed longer survival than those with PD. Evaluation of prostate and bone showed tendency to be discrepant with total judgement. Evaluation of soft tissues and prostatic acid phosphatase reflected the effect of chemotherapy. Chemotherapy often improved subjective symptoms but the effect did not parallel the total judgement in many cases. Factors influencing response of chemotherapy were mode of pretreatment, performance status, age, number of affected areas and clinical stage, but the grade at initial treatment was not correlated to response. The new criteria used in this study was valid for evaluation of response in prostatic cancer.

Topics: Acid Phosphatase; Aged; Aged, 80 and over; Antineoplastic Agents; Bone Neoplasms; Drug Evaluation; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Prostatic Neoplasms; Soft Tissue Neoplasms

Topics: Acid Phosphatase; Adenocarcinoma; Humans; Male; Neoplasm Recurrence, Local; Prostatic Neoplasms; Retrospective Studies

An eighty-two-year-old man with metastatic prostatic adenocarcinoma was treated with radiation therapy to the lumbar region of the spinal column. A rapid rise in his acid phosphatase activities developed, increasing thirty-eight-fold in two days. He died on the second day post-therapy of hemorrhagic complications. The rapid increase in acid phosphatase activity was due to release from injured or dying prostatic adenocarcinoma cells.

Topics: Acid Phosphatase; Adenocarcinoma; Aged; Aged, 80 and over; Humans; Male; Prostatic Neoplasms

The usefulness of clinical stage, serum prostatic acid phosphatase and preoperative Gleason grade in predicting final pathological stage in patients with adenocarcinoma of the prostate remains controversial. To determine the predictive value of these 3 preoperative variables we reviewed 275 patients with clinically localized disease who were treated between April 1982 and February 1986. All patients were examined preoperatively and subsequently were operated upon by 1 urologist. Serum prostatic acid phosphatase was determined in all patients by the Roy method using thymolphthalein monophosphate as the substrate. The Gleason grade of each prostatic biopsy specimen was determined preoperatively by 1 pathologist, who also examined the final pathological specimen with respect to capsular penetration, and seminal vesicle and pelvic lymph node involvement. Using logistic regression analysis with the likelihood ratio chi-square test, clinical stage and Gleason grade had a direct correlation with capsular penetration (p less than 0.0001 and less than 0.0001, respectively), seminal vesicle involvement (p less than 0.0001 and less than 0.0001, respectively) and positive lymph nodes (p less than 0.0001 and less than 0.0002, respectively). Within the normal range of values (0.0 to 0.8 IU/l.) serum prostatic acid phosphatase correlated directly with capsular penetration (p less than 0.003) and seminal vesicle involvement (p less than 0.01) but not with lymph node involvement (p equals 0.08). Again with logistic regression analysis we determined that the best predictors of final pathological stage are not individual variables but models that use combinations of preoperative variables. The models generated are as follows: capsular penetration--serum prostatic acid phosphatase and Gleason grade (p less than 0.00001), seminal vesicle involvement--clinical stage and Gleason grade (p less than 0.00001), and lymph node involvement--clinical stage and Gleason grade (p less than 0.00001). With these models probability plots have been constructed so that the final pathological stage in patients with clinically localized prostatic cancer can be predicted preoperatively.

Topics: Acid Phosphatase; Adenocarcinoma; Biopsy; Humans; Lymph Node Excision; Male; Neoplasm Staging; Pelvis; Preoperative Care; Prostate; Prostatic Neoplasms; Regression Analysis; Seminal Vesicles

Topics: Acid Phosphatase; Aged; Alkaline Phosphatase; Hormones; Humans; Male; Middle Aged; Prognosis; Prostatic Neoplasms; Retrospective Studies

Acid phosphatase (E.C. 3.1.3.2.) has been isolated from canine prostatic gland homogenates by gel permeation chromatography (AcA34 or G150), by affinity chromatography (con A-Sepharose), or by using fluid phase liquid chromatography (FPLC) using Superose 12 and Mono P columns. Acid phosphatase-enriched fractions were submitted to analytical SDS-PAGE or to analytical isoelectric focusing. A protein with a molecular weight of 30 kD (on SDS gels) was used for immunization of rabbits. The antiserum produced was cross-reactive with prostatic acid phosphatase (canine and human) as shown by immunoblotting. When applied to paraffin or plastic sections of normal canine prostate, a positive immunoreaction was found exclusively in the secretory cells. In experimentally altered glands (castration and/or hormone treatment), a varying pattern of immunoreactive cells was found. In canine prostatic carcinomas, intensively reacting cell clusters were found along with nonreactive cells. The antiserum was also slightly cross-reactive with the respective human antigen, but the cross-reactivity of an antiserum prepared against human prostatic secretory acid phosphatase with canine prostatic acid phosphatase was far more pronounced.

Topics: Acid Phosphatase; Animals; Antigens; Chromatography, Affinity; Chromatography, Gel; Dogs; Electrophoresis, Polyacrylamide Gel; Immunohistochemistry; Isoelectric Focusing; Male; Microscopy, Electron; Molecular Weight; Prostate; Prostatic Neoplasms

Topics: Acid Phosphatase; Animals; Antibodies, Monoclonal; Humans; Male; Mice; Prostate; Prostatic Neoplasms

The role of acid phosphatase in the definition of response to treatment for prostate cancer is unclear. To better define its predictive value, especially regarding survival rate, we reviewed the clinical course of 76 men with Stage D2 prostate cancer who were treated with combination chemotherapy.

Topics: Acid Phosphatase; Biomarkers, Tumor; Clinical Enzyme Tests; Combined Modality Therapy; Humans; Male; Predictive Value of Tests; Prostatic Neoplasms

The efficacy of cytotoxic agents in the treatment of prostatic cancer is difficult to evaluate because objective, measurable lesions, such as lung, liver, skin, subcutaneous and nodal metastasis are often not found. However, most of the patients with advanced prostatic cancer have bone involvement and elevated serum acid-phosphatase in addition to the primary tumor. Exact clinical trials on such cases, especially phase II studies can not be performed without appropriate evaluations of these three parameters. The criteria of these three parameters offered by various study groups are reviewed and the relevant response criteria are proposed. A stable category was thought to be useful to evaluate the efficacy on the patients with progressing disease. In our proposal, overall assessment of response involves all objective parameters including these three parameters as well as both measurable and unmeasurable disease described in the WHO handbook for reporting results of cancer treatment.

Topics: Acid Phosphatase; Androgen Antagonists; Antineoplastic Agents; Biomarkers, Tumor; Humans; Male; Prostate; Prostatic Neoplasms

Adriamycin was conjugated to an IgG1 monoclonal antibody specific for human prostatic acid phosphatase via a dextran bridge. The adriamycin-monoclonal antibody conjugate retained substantially the original immunological activity of the antibody. Antitumor effect of the conjugate in vitro was studied by its inhibition on RNA synthesis in human prostate tumor cells (LNCaP), which exhibited a higher inhibition than that by an identically prepared adriamycin-normal mouse IgG conjugate but was less than that by free adriamycin. The loss in pharmacological activity of the conjugate in vitro was proportional to the extent of dextran oxidation. Antitumor effect in vivo demonstrated that adriamycin-monoclonal antibody conjugate greatly inhibited the growth of xenografted prostate tumor, as compared with control groups, only in the early phase of experiment. These results suggested that although adriamycin conjugated to monoclonal anti-PAP antibody via a dextran bridge may be a potential reagent for experimental immunochemotherapy of prostate tumor, caution must be exercised at this stage of development.

Topics: Acid Phosphatase; Animals; Antibodies, Monoclonal; Doxorubicin; Humans; Male; Mice; Mice, Nude; Neoplasm Transplantation; Prostatic Neoplasms

The role of a staging pelvic lymph node dissection has been questioned because of its associated morbidity, especially when followed by definitive radiation therapy. Forty-nine patients with clinically localized adenocarcinoma of the prostate underwent a staging pelvic lymphadenectomy. Clinically suspected lymph nodes were submitted for frozen section analysis. A unilateral dissection was performed on 7 patients (14%), none of whom developed intraoperative or postoperative complications. The remaining 42 patients underwent bilateral pelvic lymphadenectomy, after which 26 were treated with definitive radiation therapy using the four-field box technique, and 16 received other forms of therapy (delayed androgen deprivation or hormonal manipulation). The complication rate of 19% was identical for both groups of patients. Complications consisted of 3 seromas, 1 atelectasis, 1 prolonged ileus, 1 wound infection, and 2 transient penile or scrotal edemas. Radiation therapy, therefore, did not increase postoperative morbidity.

Topics: Acid Phosphatase; Adenocarcinoma; Aged; Combined Modality Therapy; Humans; Lymph Node Excision; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Staging; Prostatic Neoplasms; Radiotherapy

Methods to disintegrate old paraffin-embedded tissue blocks for the application of DNA flow cytometry open up new possibilities for retrospective studies on the correlation between tumor cell nuclear DNA pattern and prognosis of the neoplastic disease. In the present work we used such a method to study the relationship between DNA ploidy, histopathological grade, and survival for 50 patients with prostate carcinomas diagnosed 1958-1974. Plugs of histologically identified tissue from benign and tumor areas were sampled from paraffin blocks of prostate biopsy specimens by using a 4-mm skin biopsy punch. Thirty-micron sections were cut from each plug for dewaxing and disintegration. The cell suspensions obtained were stained with 4',6-diamidino-2-phenylindole dihydrochloride and analyzed by flow cytometry. In about one-half of the cases where two or more plugs were analyzed we found a heterogeneous tumor cell nuclear DNA pattern. No apparent correlation was found between the histopathological grade and the DNA ploidy. Using Cox's multiple regression analysis, we found a significant correlation between DNA ploidy and survival of these patients (P = 0.043) when we controlled for histopathological grade (Dhom grade), acid phosphatase level, occurrence of metastases, age, year of diagnosis, and type of biopsy. The correlation between DNA ploidy and survival was just above the level of significance (P = 0.059) when Gleason grade was substituted for Dhom grade in the regression model.

Topics: Acid Phosphatase; Biopsy; Clinical Enzyme Tests; DNA, Neoplasm; Flow Cytometry; Follow-Up Studies; Humans; Male; Neoplasm Metastasis; Paraffin; Ploidies; Prognosis; Prostatic Neoplasms

A retrospective review of 102 consecutive patients with surgically staged, clinically localized prostatic carcinoma was performed to determine the relationship between pre-treatment enzymatic acid phosphatase values and histopathological extent of the tumor. Of 96 patients with normal pretreatment acid phosphatase titers (thymolphthalein monophosphate substrate) 77 (80 per cent) had values in the lower and 19 (20 per cent) had values in the upper half of the normal range. Of the latter 19 patients 16 (84 per cent) had histological evidence of extraprostatic tumor extension. Similarly, 5 of 6 patients (83 per cent) with elevated pre-treatment acid phosphatase titers had extraprostatic extension and 1 had a persistent postoperative acid phosphatase elevation that normalized with megestrol acetate therapy. Thus, 22 of 25 patients (88 per cent) with acid phosphatase values in or above the upper half of the normal range had either histological or clinical evidence of extracapsular tumor extension. By contrast, 41 of the 77 patients (53 per cent) with acid phosphatase titers in the lower half of the normal range had extracapsular extension. The predictive value for extraprostatic tumor extension of an acid phosphatase level in the upper half of the normal range was 84 per cent. Furthermore, in the 96 patients with normal acid phosphatase titers the incidence of extraprostatic tumor extension was significantly greater (p less than 0.01, chi-square) in those with values in the upper rather than the lower half of the normal range. Acid phosphatase titers in the upper half of the normal range were proportionately more common among patients with high grade and high clinical stage tumors. However, among patients with low grade and low stage tumors an acid phosphatase value in the upper half of the normal range was an independent variable that correlated with the presence of extracapsular tumor extension. These results confirm previously reported adverse prognostic implications of enzymatic acid phosphatase titers in or above the upper half of the normal range.

Topics: Acid Phosphatase; Humans; Male; Neoplasm Staging; Prognosis; Prostate; Prostatic Neoplasms; Reference Values; Retrospective Studies

A total of 25 patients with histologically proved adenocarcinoma of the prostate, whose disease was staged clinically as D2 by appropriate radiographic and nuclear medicine studies, received increasing doses of PAY 276, an antiprostatic acid phosphatase monoclonal antibody for radioimmunological imaging. The patients were divided into 5 groups of 5. Groups 1 through 5 received an infusion of 5, 10, 20, 40 or 80 mg. monoclonal antibody, respectively, 1 mg. of which was labeled to 5 mCi. of 111indium, while stable monoclonal antibody was added to achieve the desired antibody concentration. No patient had an allergic reaction, and no significant change in serial hemoglobin levels, platelet count, chemistry profile or results of urinalyses was noted. The monoclonal antibody scan visualized at least 1 lesion in 19 of 25 patients (76 per cent): 4 in groups 1 and 2, and all 15 in groups 3 to 5. With results of conventional radiography and bone scintigraphy considered definitive for metastases, monoclonal antibody scans detected 7 of 32 metastases (21.8 per cent) in group 3 (20 mg.), 31 of 58 (53.4 per cent) in group 4 (40 mg.) and 101 of 134 (75.4 per cent) in group 5 (80 mg). In group 5 the incidence of false positive and false negative scans was 2.3 per cent (3 of 132) and 24.6 per cent (33 of 134), respectively. The detection of metastatic lesions increased as the concentration of unlabeled monoclonal antibody increased. Radioimmunological imaging of prostatic cancer with antiprostatic acid phosphatase monoclonal antibody seems to be feasible.

Topics: Acid Phosphatase; Adenocarcinoma; Aged; Antibodies, Monoclonal; Bone Neoplasms; Humans; Indium; Male; Prostatic Neoplasms; Radioisotopes; Radionuclide Imaging

The authors reviewed the histologic slides of 2600 prostatic carcinomas seen at Memorial Hospital from 1963 to 1983. In ten cases, resection specimens had a predominantly endometrioid appearance. Six patients had polypoid lesions in and around the verumontanum, and one had a polypoid lesion away from the verumontanum. Two patients had no mucosal lesions and one was not cystoscoped. Histologically, the tumors showed a tall pseudostratified columnar epithelium, usually with amphophilic cytoplasm. The cells were arranged either along papillae or in complexes of large acini or in single glands. In eight of the ten cases, the endometrioid carcinomas were associated with a prior or coexistent typical microacinar prostatic adenocarcinoma. In four cases, the endometrioid pattern existed in a pure form, although in two such cases with urethral tumors, the patients had histories of successfully treated microacinar adenocarcinomas of the posterior prostatic lobe. In one case, a urethral endometrioid tumor coexisted with a small posterior lobe microacinar adenocarcinoma. In five cases, both endometrioid and microacinar carcinomas were seen, including endometrioid and microacinar carcinomas found at the same site at different times (2 cases), tumors with a predominantly endometrioid, yet focally microacinar pattern (1 case), and primary tumors where lymph node metastases had different histologic features (2 cases). Of the three patients with a pure or predominantly endometrioid pattern treated with diethylstilbestrol, two had a marked clinical response. All ten endometrioid prostatic adenocarcinomas showed prostate-specific antigen and prostate-specific acid phosphatase immunoreactivity, in contrast to none of the control uterine endometrial carcinomas. In material spanning a 20-year period, the authors have not seen a single prostatic tumor entirely analogous to the uterine endometrial carcinoma. Until such proof exists, prostatic carcinomas with endometrioid features are best classified and treated as variants of prostatic duct carcinomas.

Topics: Acid Phosphatase; Adenocarcinoma; Aged; Antigens, Neoplasm; Endometriosis; Follow-Up Studies; Histocytochemistry; Humans; Male; Middle Aged; Prostate-Specific Antigen; Prostatic Neoplasms

We have examined the level of c-myc transcripts in prostate tissue obtained from patients with both benign prostatic hyperplasia and adenocarcinoma of the prostate. A significantly higher level of c-myc transcripts is observed in patients with adenocarcinoma (P less than 0.05). In addition, a subset of patients with adenocarcinoma had levels of c-myc transcripts 2-fold higher than the mean level for this group. These preliminary results indicate that the investigation of c-myc levels as a prognostic indicator in prostatic carcinoma is warranted.

Topics: Acid Phosphatase; Aged; Gene Expression Regulation; Humans; Male; Middle Aged; Prognosis; Prostatic Hyperplasia; Prostatic Neoplasms; Proto-Oncogene Proteins; Proto-Oncogenes; RNA, Messenger; RNA, Neoplasm

A histochemical study on R1881-binding protein, prostatic acid phosphatase (PAP), prostate-specific antigen (PA) and r-seminoprotein was conducted. These parameters and histologic grades were compared to each other and with the responsiveness to endocrine therapy. A good correlation was found between histologic grade and presence or absence of R1881-binding protein in the tissue. Presence or absence of R1881-binding protein as well as histologic grade correlated well with responsiveness to endocrine therapy. Positive staining patterns of PAP, PA, and r-seminoprotein in the tissues were similar to each other, particularly between PA and r-seminoprotein. However, no correlation was found between the histologic grade and ratios of PAP, PA or r-seminoprotein-positive cells. Nor was any correlation seen between the ratio of these marker-positive cells and responsiveness to endocrine therapy.

Topics: Acid Phosphatase; Adenocarcinoma; Androgen-Binding Protein; Antigens, Neoplasm; Estrogens; Histocytochemistry; Humans; Immunoenzyme Techniques; Male; Orchiectomy; Prostate-Specific Antigen; Prostatic Neoplasms; Prostatic Secretory Proteins; Proteins; Seminal Plasma Proteins

Serum prostatic specific antigen (PSA) and prostatic acid phosphatase (PAP) were evaluated with double monoclonal radioimmunoassays. In 250 patients with prostatic cancer the normal limits were as follows: PSA 0.1-2.7 ng/ml, and PAP 1.09 +/- 0.45 ng/ml (mean +/- SD). In 91 untreated patients with non-metastatic tumours, 42.8% had PSA greater than 10 ng/ml and 18.6% had PAP greater than 2 ng/ml. In 60 untreated patients with metastatic disease PSA was greater than 10 ng/ml in 91.7%; PAP was greater than 2 ng/ml in 65%. In prolonged remission PSA was generally less than 5 ng/ml and PAP less than 2 ng/ml. Longitudinal studies of 2-4 years showed the independence of these markers and a higher correlation of changes in the PSA level and clinical status than given by parallel PAP measurements. In non-metastatic disease, PSA greater than 10 ng/ml at presentation, with or without a coincidentally raised PAP, carried an increased risk of progression within 2 years.

Topics: Acid Phosphatase; Aged; Antibodies, Monoclonal; Antigens, Neoplasm; Humans; Male; Pancreatitis-Associated Proteins; Prognosis; Prostate-Specific Antigen; Prostatic Neoplasms; Radioimmunoassay; Reference Values

The practical application of commercially available immunoperoxidase kits for prostatic specific antigen (PSA) and prostatic specific acid phosphatase (PSPH) were blindly evaluated on routinely formalin fixed and paraffin embedded tissue from 95 consecutive cases of prostatic carcinoma, 10 cases of metastases from prostatic carcinoma and 90 cases of primary or metastatic non prostatic carcinoma. Both Kits showed a diagnostic specificity of 100%. The diagnostic sensitivities were 94% (PSA) and 90% (PSPH) respectively, but concomitantly staining for PSA and PSPH improved the diagnostic sensitivity to 99%. Using the histologic grading system of Gleason both markers showed a tendency to less extensive staining in low differentiated prostatic carcinomas. It is concluded that both Kits are highly specific and highly sensitive, but negative reaction in medium or low differentiated adenocarcinomas does not rule out the possibility of prostatic carcinoma.

Topics: Acid Phosphatase; Antigens, Neoplasm; Humans; Immunoenzyme Techniques; Male; Neoplasms; Prostate; Prostate-Specific Antigen; Prostatic Hyperplasia; Prostatic Neoplasms; Reagent Kits, Diagnostic

Topics: Acid Phosphatase; Adenocarcinoma; Aged; Antigens, Neoplasm; Calculi; Clinical Enzyme Tests; Evaluation Studies as Topic; Female; Humans; Male; Middle Aged; Neoplasm Staging; Prostate; Prostate-Specific Antigen; Prostatic Hyperplasia; Prostatic Neoplasms; Time Factors

Topics: Acid Phosphatase; Adenocarcinoma; Antigens; Biopsy, Needle; Humans; Male; Prostate-Specific Antigen; Prostatic Neoplasms

Topics: Acid Phosphatase; Aged; Antigens; Humans; Male; Middle Aged; Prostate-Specific Antigen; Prostatic Neoplasms

We compared a selection of quantitative immunological methods for prostatic acid phosphatase (PAP) with routine colorimetric assays for total and tartrate-labile acid phosphatase and evaluated their relative clinical merits in the differential diagnosis of prostatic carcinoma. We also assessed a wide range of commercial control materials for suitability of use with these methods. Patients studied included 111 cases of prostatic carcinoma, 42 cases of benign prostatic hyperplasia, and 33 controls. The principles of the methods used included determination of enzymatic activity using p-nitrophenyl phosphate, RIA, immunoradiometric, and enzymoimmunometric assays. Performance characteristics for the immunological methods were inferior to manufacturers' precision and specificity claims. We identified control materials that were unsuitable for routine use. Poor discrimination between clinical groups was observed for all methods. Analysis by use of a receiver operator characteristic plot failed to improve this. We conclude that the immunological methods we studied offer no advantages over colorimetric methods in the differential diagnosis of prostatic cancer in symptomatic patients.

Topics: Acid Phosphatase; Bone and Bones; Clinical Enzyme Tests; Colorimetry; Erythrocytes; Humans; Immunologic Techniques; Isoenzymes; Liver; Male; Prostate; Prostatic Hyperplasia; Prostatic Neoplasms

Topics: Acid Phosphatase; Antigens; Histocytochemistry; Humans; Male; Neoplasm Metastasis; Prostate-Specific Antigen; Prostatic Neoplasms; Prostatic Secretory Proteins; Proteins; Seminal Plasma Proteins

Serum-acid phosphatase as measured by nine different methods, serum prostate-specific antigen, cancer antigen CA-50, and creatine kinase BB isoenzyme have been evaluated and compared with respect to efficiency in differentiating between prostate cancer and benign hyperplasia. The patient material consisted of 92 prostate cancer patients (59 untreated, and 33 previously treated), 106 patients with benign hyperplasia and 66 patients with non-prostatic urological diseases. The cancer group was classified according to the TNM-system, and also graded according to histopathological findings. The following main conclusions were drawn. Acid phosphatase activity, when measured with continuous monitoring procedure (substrate: alpha-naphthyl phosphate), showed on the average slightly, but statistically not significant higher diagnostic efficiency than when measured with conventional two-point discontinuous monitoring method (substrate: p-nitrophenyl phosphate). There was no or only marginal differences in diagnostic efficiency between activity measurements of the total acid phosphatase and the tartrate-labile fraction, and also between activity measurements and immunological measurements (PAP-RIA and PAP-IEA). Prostate-specific antigen was found to have statistically significant higher diagnostic efficiency than acid phosphatase, the former being positive in 17 of 25 patients with prostate cancer without distant metastases, and in six of 11 patients classified as T0-2 M0. Cancer antigen CA-50 and creatine kinase BB isoenzyme appeared to be of little diagnostic value. From a cost-effective point of view, total or tartrate-labile prostatic acid phosphatase activity, as measured by continuous monitoring technique with alpha-naphthyl phosphate as substrate, is suggested suitable as a first-choice parameter both for diagnostic and monitoring purposes with respect to prostate disease. Prostate-specific antigen may give additional information, and should be considered analysed on special request.

Topics: Acid Phosphatase; Adolescent; Adult; Aged; Antigens, Neoplasm; Clinical Enzyme Tests; Creatine Kinase; Humans; Isoenzymes; Male; Methods; Middle Aged; Prostatic Hyperplasia; Prostatic Neoplasms

Fifteen urinary bladder adenocarcinomas and nine bladder tumors with mixed glandular and transitional features were studied with antisera to prostate-specific antigen (PSA) and prostate-specific acid phosphatase (PSAP). The study was repeated with antisera from different companies to assess the reproducibility of the results. Of the 11 adenocarcinomas in men, three were positive for PSAP. Of the five tumors with mixed glandular and transitional features in men, one showed PSAP immunoreactivity. In the female subjects, PSAP staining was seen in two of the four adenocarcinomas and two of the four mixed glandular and transitional cell carcinomas. None of the tumors seen in either the male or female groups was considered positive for PSA.

Topics: Acid Phosphatase; Adenocarcinoma; Antigens; Clinical Enzyme Tests; Female; Humans; Immunoenzyme Techniques; Male; Prostate-Specific Antigen; Prostatic Neoplasms; Staining and Labeling; Urinary Bladder Neoplasms

Topics: Acid Phosphatase; Adult; Aged; Aged, 80 and over; Cross Reactions; Female; Humans; Immunoenzyme Techniques; Isoenzymes; Kidney Neoplasms; Male; Middle Aged; Prostate; Prostatic Hyperplasia; Prostatic Neoplasms

Topics: Acid Phosphatase; Antigens; Blood Proteins; Humans; Male; Prostate-Specific Antigen; Prostatic Neoplasms; Prostatic Secretory Proteins; Seminal Plasma Proteins

Topics: Acid Phosphatase; Antigens; Blood Proteins; Humans; Immunoassay; Male; Prostate-Specific Antigen; Prostatic Neoplasms; Prostatic Secretory Proteins; Seminal Plasma Proteins; Testosterone

Serum creatine kinase (CK) and lactate dehydrogenase (LD) isoenzymes were determined electrophoretically, along with various other biochemical markers of malignancy, in 19 patients with metastatic carcinoma of the prostate. Mitochondrial CK appeared in 15 patients, the CK-BB isoenzyme in 6. As a result, CK activity not inhibited by anti-M-subunit antibodies, CK non-M, was above the reference value in altogether 17 patients. There was a cathodic shift among the LD isoenzymes, significantly more prominent with increasing total LD, and a positive correlation between elevations of CK non-M and LD-5, suggesting a relation to tumour burden for both. An LD 'flip' (LD-1 greater than LD-2) was present in 10/15 patients. The frequency of CK non-M elevations was similar to--but not quantitatively correlated with--elevations of prostatic acid phosphatase and alkaline phosphatase. Thus, changes in CK and LD patterns are frequent in patients with prostatic cancer and must be taken into consideration when acute cardiac symptoms are evaluated in such patients.

Topics: Acid Phosphatase; Aged; Aged, 80 and over; Alkaline Phosphatase; alpha-Fetoproteins; Carcinoembryonic Antigen; Creatine Kinase; Glucose-6-Phosphate Isomerase; Humans; Isoenzymes; L-Lactate Dehydrogenase; Male; Middle Aged; Prostatic Neoplasms

In seven patients with undifferentiated carcinoma of the prostate, the immunohistochemical stain for prostate-specific antigen was negative. The stain for prostatic acid phosphatase done on the same tissue samples was diffusely positive in three, focally positive in three, and negative in one. Only the three with diffusely positive immunostaining had elevated serum acid phosphatase levels, although five had evidence of metastatic disease. All seven neoplasms were histologically similar, being composed of large cells with large nuclei, a moderate amount of cytoplasm, and indistinct cell borders. All tumors grew as broad sheets within the prostatic stroma as well as in the prostatic urethra; in six cases. Thus, prostatic carcinoma with this histologic pattern frequently loses prostate-specific antigen immunoreactivity. Awareness of this occurrence should prevent a misdiagnosis of urothelial carcinoma in such cases. The prostatic origin of these neoplasms can usually be verified by prostatic acid phosphatase immunostaining, which proves to be more sensitive in this particular setting.

Topics: Acid Phosphatase; Antigens; Carcinoma; Diagnosis, Differential; Histocytochemistry; Humans; Immunochemistry; Male; Neoplasm Metastasis; Prostate-Specific Antigen; Prostatic Neoplasms; Urethral Neoplasms

D-Trp-6-LH-RH, a long acting LH-RH agonist was given in a phase II trial to 85 patients aged 52 to 88 (mean 69) with advanced prostatic carcinoma, stage B (8 pts), C (9 pts) and D (68 pts). Twenty-five patients were previously untreated, 40 had received previous hormonal therapy but none was considered has having hormone resistant tumor; 20 patients had received surgery or radiotherapy or both. D-Trp-6-LH-RH was given s.c. at a daily dose of 500 micrograms during the first seven days, followed by 100 micrograms daily. Antitumor activity was assessed after 90 days and treatment was continued in responders. The results were the following: plasmatic levels of LH were sharply decreased and those of testosterone were in all cases under 1 ng/ml by the 90th day of treatment; urinary symptoms and bone pain disappeared or were greatly improved in almost all patients; the volume of the prostate measured by ultrasonography and/or computerized tomography regressed by more than 50% of initial volume in 44% of the 34 patients for which this parameter was evaluable; bone scintiscans were improved in 18% of evaluable patients; plasmatic levels of prostatic acid phosphatases determined by radio immuno-assay were elevated in 28 patients, 61% of which presented a decrease superior to 50% or normalisation of this parameter. No disease flare up was observed on initiation of therapy. Impotence was constant but reversible on discontinuation of therapy. No other side effect could be attributed to therapy.

Topics: Acid Phosphatase; Aged; Aged, 80 and over; Bone Neoplasms; Gonadotropin-Releasing Hormone; Humans; Male; Middle Aged; Prostatic Hyperplasia; Prostatic Neoplasms; Triptorelin Pamoate; Urination Disorders

We have compared the concentrations in serum of gamma-seminoprotein (gamma-SM) and prostate specific antigen (PSA), two antigens of prostatic origin that are synthesized independently of prostatic acid phosphatase (PAP, EC 3.1.3.2), to assess their potential in monitoring prostatic cancer. At presentation, 27/30 (90%) patients with metastases had a PSA concentration greater than 10 ng/mL, and 29/30 (97%) a gamma-SM concentration greater than 10 ng/mL; 21/61 (34%) with disease but without metastases had an abnormal content of PSA, and 23/61 (38%) an abnormal gamma-SM. Concentrations of PSA and gamma-SM were significantly correlated (r = 0.68, p less than 0.001). In 20 patients without metastases followed longitudinally, the median concentrations of gamma-SM, PSA, and PAP in the 13 patients who developed bony metastases or showed signs of local spreading of the tumor were 58 ng/mL, 34 ng/mL, and 2.1 U/L, respectively. The corresponding median values in the seven patients who remained clinically stable were 2.5 and 3.9 ng/mL, and 2.3 U/L. We conclude that either PSA or gamma-SM can warn of disease progression when PAP activities are still within normal limits.

Topics: Acid Phosphatase; Adult; Antibodies, Monoclonal; Antigens; Bone Neoplasms; Humans; Immunoenzyme Techniques; Longitudinal Studies; Male; Neoplasm Invasiveness; Neoplasm Staging; Prostate-Specific Antigen; Prostatic Hyperplasia; Prostatic Neoplasms; Prostatic Secretory Proteins; Proteins; Seminal Plasma Proteins

Prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP) have been evaluated in patients with prostate cancer, benign prostatic hypertrophy (BPH), and prostatitis. PSA has proved to be diagnostically more sensitive than PAP for the detection of prostate cancer: 95.0 per cent vs 60.0 per cent for 40 newly diagnosed cancer cases, and 97.1 per cent vs 65.7 per cent for 35 relapsed cases. This also holds true for those patients with early-stage disease: 71.4 per cent vs 0 per cent for 7 Stage A1 cases. The specificities of PSA and PAP are comparable, 96.8 per cent vs 98.9 per cent, respectively. PSA is also more sensitive for monitoring therapy, since it usually rises before PAP and always precedes clinical signs of relapse. Although PSA may be elevated more frequently than PAP in some patients with BPH and prostatitis, it is postulated that these patients with elevated serum PSA and normal serum PAP may fall into a high-risk sub-population which may have early prostate cancer or precancerous conditions not easily detectable by current clinical and diagnostic techniques. Our data suggest PSA is a sensitive useful tumor marker for the diagnosis and management of prostate cancer. In addition, PAP, in combination with PSA, may serve as a useful adjunct for differential diagnosis and confirmation of advanced stage prostate cancer.

Topics: Acid Phosphatase; Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antigens; Humans; Male; Middle Aged; Prostate-Specific Antigen; Prostatic Hyperplasia; Prostatic Neoplasms; Prostatitis

The levels of prostatic specific antigen (PSA) and prostatic acid phosphatase (PAP), both measured by radioimmunoassay, and two cancer indices given by the ratio of serum alpha-1 acid glycoprotein to prealbumin (AGP:Palb) and alpha-1 acid glycoprotein to alpha-2 HS globulin (AGP:HS) were evaluated as markers to assess the response of prostatic cancer to treatment with Zoladex, an LH-RH agonist. A rise in PSA and PAP occurred in 8/65 patients (12%) during the initial induction phase. In metastatic disease prior to treatment none of these indices was significantly different between patients who attained a sustained response and those whose response was nil or only transient. Responders and non-responders could, however, be distinguished by the levels of various analytes after treatment. At 6 months the median PSA in those who responded was 2.5 ng/ml compared with 51.5 ng/ml in the non-responders. At 12 months the figures were 3.0 and 155 ng/ml respectively. The corresponding median PAP levels were 1.4 and 19 ng/ml at 6 months and 1.3 and 18 ng/ml at 12 months. The AGP:Palb ratio was also significantly different in these two groups at 6 and 12 months. PSA appears to be the most sensitive indicator of the response to treatment. The likelihood of obtaining a prolonged clinical response can be assessed within 6 months of the start of treatment.

Topics: Acid Phosphatase; Aged; Aged, 80 and over; alpha-2-HS-Glycoprotein; Antigens; Blood Proteins; Buserelin; Goserelin; Humans; Luteinizing Hormone; Male; Middle Aged; Orosomucoid; Prolactin; Prostate-Specific Antigen; Prostatic Neoplasms; Radioimmunoassay; Testosterone

Prostatic acid phosphatase (PAP) and prostatic specific antigen (PA) were determined with a Cetus test kit (California, USA) for prostatic cancer and others. Abnormal values of PAP in untreated prostatic cancer were found in 0, 0, 50, 50, 0, 73% of stage A1, A2, CpN0, CNX, D1 and D2 cases, respectively, and those of PA were found in 25, 0, 50, 100, 100, 100% of the same stages, respectively. Grade was not related to the level of PAP or PA. Prostatic hypertrophy showed increased values of PAP and PA in 11.1% and 7.4%, respectively. The levels of PAP were not correlated to those of PA. Endocrine treatment decreased the elevated values of PAP and PA in 60% of the cases. Most of the PAP and PA levels in the cases controlled under endocrine therapy were within normal values, but after relapse most showed elevated levels.

Topics: Acid Phosphatase; Adult; Antigens; Humans; Immunoenzyme Techniques; Male; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Reagent Kits, Diagnostic

Topics: Acid Phosphatase; Antigens; Biomarkers, Tumor; Carcinoembryonic Antigen; Digestive System Neoplasms; Epitopes; Humans; Male; Prostate; Prostatic Hyperplasia; Prostatic Neoplasms; Urinary Bladder Neoplasms

The biosynthesis of distinct prostatic and lysosomal acid phosphatases is demonstrated using a human prostatic carcinoma cell line, PC-3SF12. The biosynthesis and maturation of the acid phosphatases was studied by metabolic labeling with radioactive leucine, specific immunoprecipitation, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and fluorography. Of the tartrate-inhibitable acid phosphatase activity in PC-3SF12 cells, 60% is lysosomal and 10% is prostatic. The lysosomal-type acid phosphatase is synthesized as precursor with a molecular weight of 68,000, some of which is converted to higher-molecular-weight precursor polypeptides (Mr 71,000 and 77,000). The multiple forms of the precursors are due to differences in the carbohydrate chains on the enzyme because biosynthesis in the presence of tunicamycin eliminates the precursor multiplicity. The initial precursor (Mr 68,000) is processed to a mature polypeptide (Mr 49,000), via intermediates with molecular weights of 62,000 and 59,000. The mature polypeptide is degraded to smaller polypeptides with molecular weights of 30,000, 28,000, and 25,000. Precursor polypeptides of the lysosomal-type enzyme are secreted in the medium. Prostatic acid phosphatase is synthesized as a precursor with a molecular weight of 110,000, which is processed via several intermediates (Mr 99,000-93,000, 77,000, and 55,000) to a mature polypeptide with a molecular weight of 49,000. Particularly during cell homogenization, or lysis, the mature polypeptide is rapidly degraded to an immunoprecipitable polypeptide with a molecular weight of 20,000. None of these polypeptides is secreted in detectable amounts into the medium. Precursors and mature and smaller polypeptides are present in human prostate extract and seminal fluid. Proteolytic degradation of prostatic acid phosphatases in cells and tissues is probably catalyzed by a plasmin-like or related trypsin-like enzyme because degradation of the mature prostatic phosphatase polypeptide is completely prevented by addition of the plasmin inhibitor bovine pancreatic trypsin inhibitor. Prostatic- and lysosomal-type acid phosphatases are eventually stored at least in part in two different types of cell organelles. Testosterone does not influence the biosynthesis and secretion of either acid phosphatase in this cell line.

Topics: Acid Phosphatase; Carcinoma; Cell Compartmentation; Cell Line; Fibrinolysin; Humans; Immunologic Techniques; Lysosomes; Male; Molecular Weight; Prostate; Prostatic Neoplasms; Semen; Testosterone; Trypsin Inhibitors; Tunicamycin

Forty patients with stage D2 prostatic carcinoma were treated for up to 30 months with D-Trp-6-LH-RH. The analog was given s.c. once daily at a dose of 1 mg/day for the first 7 days. Subsequently, the dose was reduced to 100 micrograms/day. In follow-up studies, 30 men continued this therapy for up to 24 months. Blood samples were taken before the injection of the analog and 1, 2, 4, and 6 hours later. Serum LH, FSH, and testosterone levels were measured by RIA every month for 2 years. The initial administration of 1 mg D-Trp-6-LH-RH caused a marked elevation of LH and FSH, which lasted more than 24 hours. However, 1 month later and throughout the therapy, the basal values of LH and FSH were below the normal range and no increase in serum gonadotropins levels was obtained after administration of the analog. Initial plasma testosterone was within normal limits, but during treatment with D-Trp-6-LH-RH it fell to castration levels, and no increases were seen during the 6 hours following the injection of the analog. These results show that chronic administration of D-Trp-6-LH-RH, at the doses used, blocks the pituitary-gonadal axis and that the escape phenomenon from the effects of the LH-RH agonists-induced blockade does not occur under our conditions in contrast to observations of Kerle et al with the I.C.I. Analog 118630 (8). The accumulated results reinforce the view that long-term therapy with agonists of LH-RH is the preferred alternative to surgical castration or therapy with estrogens in men with metastatic prostate cancer.

Topics: Acid Phosphatase; Antineoplastic Agents; Gonadotropin-Releasing Hormone; Gonadotropins, Pituitary; Humans; Male; Prostate; Prostatic Neoplasms; Testosterone; Triptorelin Pamoate

Various approaches to hormonal treatment of prostate carcinoma are discussed. Eighty-one patients with prostatic carcinoma, eight with stage B, nine with stage C, and 64 with stage D disease, were treated subcutaneously daily for 3 months with the LH-RH agonist D-Trp-6-LH-RH (Decapeptyl) in order to evaluate the incidence of remissions according to WHO recommendations for oncologic trials. The findings were compared to those obtained with other hormonal therapies of prostatic carcinoma according to the statistical method of "expected response rate" as adapted by Lee and Wesley for phase II trials. Treatment with D-Trp-6-LH-RH greatly reduced serum LH and testosterone levels without raising serum prolactin. After 1-2 weeks of therapy, there was relief of subjective symptoms and a reversal of the signs of prostatism as well as a marked decrease in bone pain. At 90 days 52 patients had complete relief of prostatism and 21 had only mild signs and symptoms. Seventy patients were experiencing no bone pain and an additional six had only mild pain. Prostatic size, evaluated by rectal examination and transabdominal ultrasonography, reverted to normal in 26.4% of patients (complete remission) and was reduced by more than 50% in an additional 17.6% (partial remission), the overall rate of complete plus partial regression of prostatic enlargement being 44%. Scans showed a major improvement of bone lesions in 14.8% of cases. This response increased to 37% after more than 6 months of follow-up. Prostatic acid phosphatase levels were decreased by more than 50% in 61% of the patients, but this test appears to be a less valid marker than the lipid-associated sialic acid (LASA). The increase in LASA before treatment and a reduction after treatment can frequently be correlated with the objective volume of the neoplasms. No flare-up of the disease was encountered, and there were no side effects except for impotence. Statistical analyses of results by the method of Lee and Wesley indicated that the incidence of complete and partial regression (CR and PR) observed with D-Trp-6-LH-RH was not significantly different from that recorded in previous studies for another LH-RH analog, Buserelin. However, CR and PR obtained with D-Trp-6-LH-RH (44%) were significantly higher than with subcapsular orchiectomy (22%). Hormonal effects and some other actions of D-Trp-6-LH-RH were compared and contrasted with those produced by castration, estrogens, antiandrogens, and progestogens.(ABSTRACT

Topics: Acid Phosphatase; Aged; Aged, 80 and over; Carcinoma; Drug Administration Schedule; Drug Evaluation; Gonadotropin-Releasing Hormone; Humans; Luteinizing Hormone; Male; Middle Aged; Prostatic Neoplasms; Testosterone; Triptorelin Pamoate

Clinical and experimental studies are described on the effects of a gonadotropin-releasing hormone (GnRH) agonist (A) and antagonist (Ant.) on testicular endocrine function. Testicular effects of long-term gonadotropin suppression by GnRH-A were assessed during treatment of prostatic cancer patients. The testis tissue removed after 6 months of A treatment had less than 5% of the testosterone(T)-producing capacity in comparison to testis tissue removed from untreated control patients. However, the LH receptors (R) and responsiveness of T output to LH stimulation in vitro were unchanged. FSH-R decreased by 70%. Hence, despite suppression of gonadotropins and testicular androgen production during long-term GnRH-A treatment the responsiveness to exogenous gonadotropins is maintained. The testicular effects of a gonadotropin suppression induced with GnRH-Ant. and testicular GnRH-R blockade were studied in rats. Besides decreases of gonadotropins and testicular T, systemic Ant. treatment decreased testicular Prl-R, but had no effect on LH-R or FSH-R. Bromocriptine-induced hypoprolactinemia, in contrast, decreased LH-R but had no effect on Prl-R. The results indicate reciprocal regulation of LH-R and Prl-R, and that testicular steroidogenesis and LH-R are under differential regulation, the former by LH, the latter by Prl. In another study, testicular GnRH-R, and consequently the action of a putative testicular GnRH-like factor, were blocked by unilateral intratesticular infusion of Ant. (1 week, Alzet osmotic pumps). The treatment resulted in 90% occupancy of testicular GnRH-R in the Ant.-infused testes, and this was associated with decreased levels of R for LH, FSH and Prl, and of T. The results indicated that the testicular GnRH-R have a physiological function in subtle stimulation of Leydig cell functions.

Topics: Acid Phosphatase; Aged; Animals; Buserelin; Follicle Stimulating Hormone; Humans; Luteinizing Hormone; Male; Middle Aged; Pituitary Hormone-Releasing Hormones; Prostatic Neoplasms; Rats; Receptors, Cell Surface; Receptors, FSH; Receptors, LH; Receptors, LHRH; Receptors, Prolactin; Testis; Testosterone

Topics: Acid Phosphatase; Adrenalectomy; Antineoplastic Agents; Biopsy, Needle; Carcinoembryonic Antigen; Combined Modality Therapy; Diethylstilbestrol; Gonadotropin-Releasing Hormone; Humans; Male; Neoplasm Staging; Orchiectomy; Prostate; Prostatectomy; Prostatic Neoplasms; Radiotherapy

Topics: Acid Phosphatase; Aged; Buserelin; Delayed-Action Preparations; Drug Evaluation; Humans; Injections, Subcutaneous; Male; Middle Aged; Prostatic Neoplasms; Testosterone

The serum protein binding secretory prostatic acid phosphatase (PAP) and lysosomal placental acid phosphatase (LAP) was purified using affinity chromatography on gels containing immobilized acid phosphatases. The protein, which could be eluted from these enzyme affinity gels only with 0.05 mol/l HCl (pH 2.0), was shown to be apolipoprotein A-I (apo A-I), the main structural protein of high density lipoprotein (HDL).

Topics: Acid Phosphatase; Apolipoprotein A-I; Apolipoproteins A; Chromatography, Affinity; Humans; Isoelectric Focusing; Isoenzymes; Lipoproteins, HDL; Lysosomes; Male; Placenta; Prostate; Prostatic Neoplasms

The clinical course of 25 patients with clinical stage C adenocarcinoma of the prostate who had pre-treatment elevations of the prostatic acid phosphatase (Roy test) was analyzed retrospectively. All patients were treated with definitive external beam radiation therapy at our hospital between 1974 and 1980. Of the 25 patients 17 (68 per cent) have had disease progression. The median time to treatment failure for this group was 27 months (range 10 to 101 months), and the over-all median survival for these patients has not been reached (range 16 to 120 months). Local control of disease was achieved in 84 per cent (21 of 25) of the patients. The control group consisted of 75 consecutive age-matched patients with normal pre-treatment prostatic acid phosphatase levels whose disease was identically staged and treated at our hospital from July 1977 to January 1979. The median time to disease progression in this group has not yet been reached. Of these 75 patients 24 (32 per cent) have had disease progression within a median time of 38 months. Therefore, an elevated pre-treatment prostatic acid phosphatase value is a harbinger of systemic disease and indicates that radiotherapy will be significantly (p equals 0.002) less effective as a definitive local therapeutic modality.

Topics: Acid Phosphatase; Adenocarcinoma; Aged; Humans; Male; Middle Aged; Prognosis; Prostate; Prostatic Neoplasms; Radiotherapy, High-Energy; Retrospective Studies

Topics: Acid Phosphatase; Adenocarcinoma; Black People; Bone Neoplasms; Humans; Immunoenzyme Techniques; Male; Microscopy, Electron; Middle Aged; Prostatic Neoplasms; Testicular Neoplasms

At present no single test is effective in detecting prostatic carcinoma, although some newer tests show promise. Several investigators are working to increase the specificity and sensitivity of various radioimmunoassays for prostatic cancer detection, but to date this research has not been rewarding. Careful rectal examination and close attention to the patient's symptoms may still be the only keys to diagnosis. Patients in their 50s and 60s with acute onset of symptoms have a relatively high incidence of prostatic carcinoma. These patients should have a rectal examination and aspiration biopsy cytology of any suspicious areas found on examination. Possibly these patients should have aspiration biopsy cytology even in the absence of suspicious findings to screen for disease before it becomes an obvious clinical entity. This is perhaps the best approach to prostatic cancer, ie, attack at a time in which there are fewer cells and a greater chance of cure.

Topics: Acid Phosphatase; Biopsy, Needle; Bone and Bones; Chronic Disease; Humans; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Staging; Physical Examination; Prostate; Prostatic Neoplasms; Radionuclide Imaging; Ultrasonography

Gastrointestinal bleeding was the presenting manifestation in four patients without readily apparent prostate cancer. Three of these patients had laboratory evidence of acute disseminated intravascular coagulation (DIC) and one patient had a friable rectal mass. The diagnosis of prostate cancer was made in three patients by employing an immunoperoxidase technique for prostatic acid phosphatase in metastatic foci. Dramatic resolution of DIC occurred in two patients following hormone therapy. Radiation therapy was effective in controlling bleeding in another patient. Two patients are alive with no further bleeding episodes at 8 and 18 months follow-up, respectively. In patients who present with a bleeding diathesis and adenocarcinoma of unknown primary, it is important to consider prostate cancer because of its frequent and prolonged responsiveness to hormonal therapy.

Topics: Acid Phosphatase; Aged; Disseminated Intravascular Coagulation; Gastrointestinal Hemorrhage; Humans; Immunoenzyme Techniques; Male; Middle Aged; Prostatic Neoplasms

Twenty prostate glands from patients with either high-grade papillary tumors (19 patients, 15 of whom also had peripheral carcinoma in situ) or multifocal carcinoma in situ (1 patient) of the bladder who underwent cystoprostatectomy were studied histologically by mapping. Prostatic duct involvement by urothelial carcinoma was noted in nine patients, two with extensive involvement and seven with focal involvement confined to periurethral ducts. Carcinoma in situ of the bladder was observed in each of the nine patients and intraepithelial permeation appeared to be the predominant manner of spread of cancer cells into the prostate. The prostatic involvement was clinically silent and it may be a potential source of failure of conservative modalities of treatment of high-grade bladder cancer. A routine diagnostic transurethral prostatic biopsy may be recommended in the workup of patients with carcinoma in situ and high-grade carcinomas of the bladder. An incidental observation was the presence of 14 occult prostatic adenocarcinomas.

Topics: Acid Phosphatase; Adenocarcinoma; Aged; Carcinoma in Situ; Ejaculatory Ducts; Histocytochemistry; Humans; Immunoenzyme Techniques; Male; Middle Aged; Neoplasm Invasiveness; Neoplasms, Multiple Primary; Prostate; Prostatectomy; Prostatic Neoplasms; Urethral Neoplasms; Urinary Bladder Neoplasms

A patient who was treated with estrogens for carcinoma of the prostate was later diagnosed with apparent primary cancer of the male breast. He received chest-wall radiation therapy with curative intent. Later, immunodiagnosis by immunoperoxidase staining for human prostate-specific acid phosphatase of the breast tissue revealed that the patient actually had metastatic prostate cancer to the breast rather than primary breast cancer secondary to estrogen therapy. Use of highly specific peroxidase-antiperoxidase tissue staining for human prostate-specific acid phosphatase is recommended to differentiate primary male breast cancer from metastatic prostate cancer.

Topics: Acid Phosphatase; Adenocarcinoma; Aged; Breast Neoplasms; Diagnosis, Differential; Humans; Immunoenzyme Techniques; Male; Prostate; Prostatic Neoplasms

Topics: Acid Phosphatase; Counterimmunoelectrophoresis; Humans; Immunoenzyme Techniques; Male; Prostatic Neoplasms; Radioimmunoassay

Two cases of calcitonin-producing carcinomas of the prostate are reported. Light microscopical, immunohistochemical, and ultrastructural investigations have been performed. These tumors displayed a remarkable dual, endocrine and common epithelial (exocrine), differentiation. However, they presented two different architectural growth patterns. Of particular interest, numerous calcitonin cells were immunocharacterized. In addition, the endocrine component could harbour carcinoembryonic antigen, serotonin, human chorionic gonadotrophin, and prostate-specific acid phosphatase immunoreactive cells. Ultrastructural analysis confirmed the presence of numerous endocrine cells. These findings are not unexpected, since calcitonin, serotonin, and human chorionic gonadotrophin immunoreactive cells are normal and constitutive inhabitants of prostate gland. In the current cases, calcitonin cells showed a strong carcinoembryonic antigen immunoreactivity, as observed also in thyroidal C-cells. This peculiar kind of prostatic carcinoma might be compared to certain thyroidal tumors of intermediate type coupling parafollicular and follicular differentiation.

Topics: Acid Phosphatase; Adenocarcinoma; Aged; Aged, 80 and over; Calcitonin; Carcinoembryonic Antigen; Chorionic Gonadotropin; Fluorescent Antibody Technique; Humans; Immunoenzyme Techniques; Male; Microscopy, Electron; Prostate; Prostatic Neoplasms; Serotonin

Topics: Acid Phosphatase; Aged; Alkaline Phosphatase; Body Weight; Cisplatin; Drug Evaluation; Humans; Male; Neoplasm Metastasis; Prostatic Neoplasms

Human prostatic acid phosphatase isoenzyme 2 (HPAcP-2) was isolated from semen. This purified enzyme was immunized to rabbit to produce polyclonal antibodies. The specificity of the antibodies was tested by Western blot transfer method. Rabbit IgG-peroxidase conjugate was prepared from the antiserum and used to localize HPAcP-2 in prostatic carcinoma. It was found that in the tumor glandular acinus the normal basal cells were replaced by tumor cells containing reaction product. In the tumor cells, the reaction product was seen in the cisternae of rough endoplasmic reticulum (ER) and Golgi apparatus. The secretory vesicles which contained reaction product-stained granules and some amorphous material were seen to fuse with the apical plasma membrane and discharged their content into the glandular lumen. On the other hand, some secretory vesicles in the tumor cells facing to the basement membrane also discharged their similar content into the extracellular spaces. Reaction product-stained granules were found in the interstitial spaces surrounding the tumor cells. These findings suggest that HPAcP-2 is synthesized on the bound ribosomes and discharged into the cisternae of rough ER. The molecules are transported to the Golgi cisternae. After concentration and packaging, HPAcP-2 molecules are then transferred to the secretory vesicles, and discharged into the glandular lumen and to the extracellular spaces. The isoenzyme released in the extracellular space may reach the blood stream through the interstitial spaces or the lymphatic system, resulting in the elevation of serum HPAcPase level in some prostatic cancer patients.

Topics: Acid Phosphatase; Carcinoma; Humans; Immunochemistry; Male; Prostatic Neoplasms

Methotrexate (MTX) was conjugated to an immunoglobulin G1 (IgG1) monoclonal antibody specific for human prostatic acid phosphatase (PAP) by the active ester method. The molar ratio of MTX to IgG was 14. MTX-monoclonal antibody conjugate retained substantially the original PAP-binding inhibition activity of the monoclonal antibody. Both MTX-monoclonal antibody conjugate and an identically prepared MTX-normal mouse IgG conjugate preserved 90% of the original dihydrofolate reductase inhibitory activity of MTX. [3H]MTX conjugated to monoclonal anti-PAP antibody was significantly accumulated more in PAP-producing human prostate tumor LNCaP cells than its normal mouse IgG counterpart. No statistical difference was found between the uptake of [3H]MTX conjugated to monoclonal antibody and that of [3H]MTX conjugated to normal mouse IgG by control PAP nonproducing thyroid tumor cells (TT). The antitumor effect of the conjugate was evaluated in vitro by its inhibition on deoxy[6-3H]uridine incorporation into LNCaP cells. The inhibition by MTX-monoclonal antibody conjugate was significantly higher than that by MTX-normal mouse IgG conjugate at 8 micrograms of drug per ml, although it was significantly less than that by free MTX. However, an in vivo tumor and tissue distribution study of [3H]MTX and its conjugates revealed that, 5 days after i.v. administration, [3H]MTX conjugated to monoclonal antibody was preferentially accumulated in LNCaP prostate tumor. Tumor:blood ratios for [3H]MTX, [3H]MTX-monoclonal antibody conjugate, and [3H]MTX-normal mouse IgG conjugate were 1.47, 5.06, and 1.26, respectively. Preliminary results obtained from a pilot study with a small number of animals demonstrated that multiply injected MTX-monoclonal antibody conjugate retarded the growth of xenografted prostate tumor (LNCaP) as compared with the control groups, including free MTX which showed a shorter period of therapeutic effectiveness. This study suggests that MTX conjugated to monoclonal anti-PAP antibody could be a potential reagent for experimental immunochemotherapy of prostate tumor, should the initial in vivo data be extended and confirmed.

Topics: Acid Phosphatase; Animals; Antibodies, Monoclonal; Deoxyuridine; Folic Acid Antagonists; Humans; Immunoglobulin G; Male; Methotrexate; Mice; Mice, Nude; Prostate; Prostatic Neoplasms; Tritium

Data from a recent survey of patterns of care for prostatic cancer sponsored by the American College of Surgeons suggest several trends compared to similar data from a decade ago. The observed differences include increased diagnosis of localized cancer, and increased use of acid phosphatase determinations, bone scans, radical retropubic prostatectomy, radiotherapy (particularly interstitial techniques) and orchiectomy. In contrast, use of bone surveys, perineal prostatectomy and hormonal therapy has decreased. Transurethral resection continues to be the most common means to establish the diagnosis of prostatic cancer but the data do suggest that in more patients the tumors are being staged and graded. Five-year survival rates appear to be improving for all stages, and for white and black patients. Survival of black patients continues to lag behind that of white subjects, presumably owing to the more advanced stage of disease at diagnosis observed in these data. These findings may have important implications for understanding trends in survival of patients with this disease.