bromochloroacetic-acid and Prostatic-Diseases

Benign prostatic hyperplasia and prostate cancer arise as a consequence of changes in the balance between cell division and differentiation. Little, however, is known about the control of this process. Stem cells are a small population of cells that divide occasionally to produce transit-amplifying cells that in turn produce the differentiated cell types of the tissue. It is believed that cancer cell proliferation is also driven by stem cells. We have shown that around one in 200 prostate epithelial cells have characteristics of stem cells and that these cells are contained within a population with a distinct keratin expression pattern. Work is now ongoing to identify markers for these cells that will allow us to study the role they play in prostatic disease.

Topics: Cell Differentiation; Cells, Cultured; Epithelial Cells; Humans; Integrins; Keratins; Male; Prostate; Prostatic Diseases; Stem Cells; Transforming Growth Factor beta

A variety of small acinar lesions of the prostate can mimic prostate cancer in punch biopsies and in transurethral resection material. The first part of this review deals with differential diagnostic problems of the central and transition zone, including atypical adenomatous hyperplasia of the prostate, atrophic processes, sclerosing adenosis, basal cell hyperplasia, and low-grade adenocarcinoma. The second part deals with differential diagnostic problems in the peripheral zone: prostatic intraepithelial neoplasia, postatrophic hyperplasia, Cowper's glands, seminal vesicles, and ductal and intraductal carcinoma. Finally, atypical and small acinar proliferations are described. Diagnostic perspectives are discussed. proliferations (ASAP) that cannot be integrated into any of the well-established diagnostic entities [1, 16, 22, 41]. The relevant glandular proliferations of the central, transitional and peripheral zones of the prostate are discussed here with reference to the related carcinomas.

Topics: Adenocarcinoma; Atrophy; Diagnosis, Differential; Humans; Keratins; Male; Precancerous Conditions; Prostate; Prostate-Specific Antigen; Prostatic Diseases; Prostatic Hyperplasia; Prostatic Intraepithelial Neoplasia; Prostatic Neoplasms

To describe the morphology of focal prostatic atrophy and propose a comprehensive histologic classification for a proper diagnostic recognition.. A broad immunohistochemical study was performed as an adjunct to its recognition as well as a contribution to pathogenesis.. A morphologic continuum was seen on needle biopsies. Chronic inflammation was present only in complete atrophy. Immunohistochemical findings in partial atrophy are similar to normal acini. Luminal compartment in complete atrophy shows aberrant expression of 34betaE12 favoring an intermediate phenotype. ERG negativity in all variants of atrophy may have value in the identification of the lesion.. The morphologic findings favor a continuum probably partially preceding complete atrophy. Chronic inflammation may be a secondary phenomenon seen only in complete atrophy. Overexpression in complete atrophy of glutathione S-transferase pi relates to oxidative stress possibly related to chronic ischemia, of c-Met favors the concept that intermediate cells may be target for carcinogenesis, and of CD44 may be related to the recruitment of inflammatory cells.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Atrophy; Biopsy, Needle; Diagnosis, Differential; Humans; Hyaluronan Receptors; Immunohistochemistry; Kallikreins; Keratins; Male; Middle Aged; Prostate; Prostate-Specific Antigen; Prostatic Diseases; Prostatic Intraepithelial Neoplasia; Prostatic Neoplasms; Sclerosis

Claudins are a family of approximately 23 integral membrane tight junction (TJ) proteins that maintain cell polarity and paracellular barrier functions in epithelial and endothelial cells. Although Claudin-1 was demonstrated to be typically downregulated in various cancers, the precise expression patterns of this protein in normal and neoplastic tissues remain poorly characterized.. Using immunohistochemistry, the expression of Claudin-1 was investigated in prostate tissue samples arranged in a tissue microarray (TMA) format and comprising elements of normal prostatic epithelium (n = 6), benign prostatic hyperplasia (BPH; n = 38), prostatic intraepithelial neoplasia (PIN; n = 11), and prostate adenocarcinoma (n = 48). The Claudin-1 expression pattern was compared with that of the basal cell-specific markers, p63, and HMW cytokeratin (34betaE12), by employing double-labeling techniques in conjunction with image analysis methods utilizing color deconvolution algorithms.. In benign prostatic epithelium, pronounced Claudin-1 expression was observed in the basal cell layer with no staining in luminal cells. Prostate adenocarcinoma specimens from 98% (47/48) patients lacked Claudin-1 immunostaining, and no cases contained >5% immunopositive tumor cells.. Claudin-1 immunohistochemistry should be considered for use as a new diagnostic tool for distinguishing malignant from benign lesions of the prostate.

Topics: Claudin-1; Humans; Immunohistochemistry; Keratins; Male; Membrane Proteins; Prostatic Diseases; Prostatic Hyperplasia; Protein Array Analysis

Topics: Cell Division; Crystallization; Electron Probe Microanalysis; Glycoproteins; Humans; Inclusion Bodies; Keratins; Male; Microscopy, Immunoelectron; Prostate; Prostatic Diseases; Prostatic Neoplasms; Sulfur

Topics: Antibodies, Monoclonal; Biomarkers, Tumor; Humans; Immunohistochemistry; Keratins; Male; Predictive Value of Tests; Prostatic Diseases; Prostatic Neoplasms; Tissue Fixation

Prostate-specific antigen (PSA) cannot differentiate benign prostatic hyperplasia (BPH), from prostatitis, or prostate cancer in the range of 4.0-10 ng/ml. An accurate cytologic or histologic assessment is necessary to confirm the proper diagnosis. The nature of a biopsy tends to make it a selective test not frequently repeated. We are reporting a technique employing semen as a source for the differential diagnosis of prostate epithelial cells.. Eleven vasectomized and nonvasectomized prostate cancer patients provided semen samples (stage T1 to T2). Two patients provided repeat samples. In addition, 15 vasectomized or nonvasectomized individuals without evidence of disease provided semen samples. Three million cells fixed with 50% ethanol were stained by an antibody (7E11.C5) to prostate-specific membrane antigen (PSMA), Hybritech Antibody (399) to PSA, and cytokeratin 8 and 18. In addition to the antibodies described, a DNA stain To-Pro 3 was used to identify 2n-4n DNA containing cells. A dual laser, Becton Dickinson FACSCaliber cytometer, was used to analyze the samples.. All semen specimens contained diploid, cytokeratin 18-positive epithelial cells regardless of disease status. A clear difference between prostate cancer and normal prostate cell samples was observed using staining with 7E11.C5. The ratio of prostatic cells in the total epithelial cell population (PSMA:cytokeratin ratios) was calculated for each specimen. A retrospective study of sixteen semen samples from 11 prostate cancer patients had a mean PSMA:cytokeratin ratio of 0.57, whereas the samples from 15 patients without evidence of cancer had a mean PSMA:cytokeratin ratio of 0.11. This difference was significant. PSA staining was variable and inconsistent.. This report demonstrates that human semen contains prostate cells that can be characterized and used in the clinical diagnosis of prostate cancer.

Topics: Adult; Antigens, Surface; Biomarkers, Tumor; Carboxypeptidases; Diagnosis, Differential; Flow Cytometry; Glutamate Carboxypeptidase II; Humans; Keratins; Male; Middle Aged; Prostate; Prostatic Diseases; Retrospective Studies; Semen

Prostatic epithelium basically consists of secretory-luminal, basal and endocrine-paracrine cells. Immunohistochemical procedures are frequently used for showing the cells reflecting different differentiations. In this study, 40 prostatic tissue specimens submitted to the Department of Pathology of Inönü University, Research Hospital, between 1991 and 1996 were examined. Half of the cases were diagnosed as cancer and the other half had various benign lesions. Of the cases 22.5% (n = 9) were needle biopsy material whereas the remainder, 47.5% (n = 19), were from prostatectomy and 30% (n = 12) were transurethral resection of the prostate (TURP) specimens. High molecular weight anti-cytokeratin antibodies (HMW anti-cytokeratin) stained basal cells both in all normal prostatic tissue and benign prostatic lesions, but in the majority of cancers (70%, n = 14) negative immunoreactivity was seen. Nevertheless, in some of the cancer cases (30%, n = 6) basal cell anti-cytokeratin staining was shown. Negative immunoreactivity with HMW anti-cytokeratin is important in distinguishing between malignant and benign lesions, whereas positive staining is not every time in favour of benign lesions. With the usage of prostate specific antigen (PSA) it was seen that all of the malignant and benign prostatic lesions stained positively. Basal cells in hyperplastic glands were not stained with this stain. Irregular, and in some areas, intense (PSA) immunoreactivity is present in precancerous and malignant lesions. Endocrine cells, which are represented with Chromogranin-A (Chr-A) immunoreactivity and reflecting neuroendocrine differentiation, are present in 75% (n = 15) of benign lesions and in 50% (n = 10) of cancer cases. It was thought that the lesser number of these cells in neoplastic lesions in comparison to the non-tumoral lesions is correlated with the disorder of mechanism that regulates the cell growth. Both in neoplastic and non-tumoral tissues the prostatic epithelial cells showed the three markers, namely HMW anti-cytokeratin, PSA, and Chr-A, which may reflect the multidirectional differentiation of these cells from a pluripotent origin.

Topics: Adenocarcinoma; Biomarkers, Tumor; Biopsy, Needle; Cell Division; Chromogranin A; Chromogranins; Diagnosis, Differential; Epitopes; Humans; Keratins; Male; Prostate-Specific Antigen; Prostatectomy; Prostatic Diseases; Prostatic Hyperplasia; Prostatic Neoplasms

Intraluminal contents in benign and malignant prostate glands from 10 prostatectomies were studied by light and electron microscopy as well as X-ray microanalysis. Ultrastructural immunolocalization of keratin and analysis of the pattern of lectin binding for wheat germ agglutinin (WGA), peanut agglutinin (PNA) and soy bean agglutinin (SBA) were performed. By electron microscopy corpora amylacea were composed of bundles of fibrils and occasional interspersed electron-dense areas. Crystalloids on the other hand were relatively electron-dense formations without any identifiable substructure. Complete or partial enclosement of the crystalloids by the fibrillary or electron-dense material that forms the corpora amylacea was often seen. Histochemistry localized keratin and glycoproteins in all types of intraluminal contents. However, the proportion of these components varied. Keratin and WGA binding were identified primarily in the amorphous secretions and in corpora amylacea, but were only minimally represented in crystalloids. PNA and SBA were found predominantly in crystalloids, with only minimal amounts identified in corpora amylacea. By X-ray microanalysis sulfur was identified primarily in crystalloids and surrounding amorphous secretion, but lesser quantities of sulfur were also found in corpora amylacea. In summary, the morphological and histochemical findings indicate that the intraluminal contents in benign and malignant glands form a continuous spectrum and are largely composed of material derived from the components of lining cells.

Topics: Adenocarcinoma; Crystallization; Cytoplasmic Granules; Humans; Immunohistochemistry; Inclusion Bodies; Keratins; Lectins; Male; Prostate; Prostatic Diseases; Prostatic Neoplasms; Sulfur; X-Rays

To understand the role of estrogen in the pathogenesis of benign prostatic hyperplasia, expressions of estrogen receptor (ER) mRNA and ER protein by in situ hybridization and by immunohistochemistry, respectively, were investigated in human prostatic tissues. In non-malignant region, ER mRNA and ER protein were found in cytoplasm and nucleus, respectively, of stromal cells, but not in glandular epithelial and basal cells. In benign regions, ER mRNA/ER protein positive cells were found in fibromyoadenomatous and myoadenomatous hyperplasia, but not in adenomatous hyperplasia. A striking feature was periacinar arrangement of ER mRNA/ER protein positive stromal cells in all prostate carcinoma treated with androgen withdrawal. The ER mRNA/ER protein positive cells were immunohistochemically identified as fibroblasts, myoblasts, and smooth muscle cells. These results indicate that stromal cells are the primary target of estrogen in prostate, and that androgen withdrawal upregulates the expression of ER gene.

Topics: Aged; Aged, 80 and over; Base Sequence; Desmin; Humans; Immunohistochemistry; In Situ Hybridization; Keratins; Male; Middle Aged; Molecular Sequence Data; Prostate; Prostatic Diseases; Prostatic Hyperplasia; Prostatic Neoplasms; Receptors, Estrogen; RNA, Messenger; Vimentin

Numerous reports have claimed that because acidic mucin is absent in benign prostatic glands and is present in some prostatic adenocarcinomas, this stain may be an adjunctive aid in the diagnosis of adenocarcinoma of the prostate. However, adenosis that mimics low-grade adenocarcinoma has not been evaluated to date. We studied 28 foci of adenosis for the presence of high iron diamine-alcian blue (HID-AB). Fifteen foci of adenosis (54%) showed strong staining for HID-AB; staining was diffuse in 11 cases and focal in four cases. An additional two cases (7%) showed equivocal staining. The remaining 11 cases (39%) lacked positivity. All cases of adenosis were verified with immunohistochemistry for keratin 903, a basal cell-specific antibody. This study demonstrates the limited use of acid mucin staining in the diagnosis of adenocarcinoma. The finding of HID-AB positivity in occasional isolated benign small prostatic glands within hyperplastic nodules suggests that acid mucin secretion may be a reflection of gland size or proliferation rather than evidence that adenosis is related to adenocarcinoma of the prostate.

Topics: Adenocarcinoma; Biomarkers, Tumor; Diagnosis, Differential; Histocytochemistry; Humans; Immunohistochemistry; Keratins; Male; Mucins; Prostate; Prostatic Diseases; Prostatic Neoplasms

Topics: Diagnosis, Differential; Humans; Immunohistochemistry; Keratins; Male; Prostatic Diseases; Prostatic Neoplasms

Sclerosing adenosis of the prostate is a rare lesion characterized by the proliferation of variably sized glands in a cellular stroma. We report light microscopic, immunohistochemical, and ultrastructural studies in 22 examples from 15 patients. Two cases were identified in 100 consecutive prostates embedded by a whole organ method, giving a prevalence of 2%. Antibodies directed against the following antigens were used: high-molecular-weight cytokeratin (CKH; 34 beta E12); cytokeratin (CK; AE1/AE3), prostatic acid phosphatase (PAP), prostate-specific antigen (PSA), S-100 protein, muscle-specific actin (HHF35), and vimentin (Vim). Cells within the glandular component demonstrated positive reactivity for CK, CHH, PSA, and PAP, indicating a prostatic epithelial origin. In addition, a distinct population of cells reacting for muscle-specific actin and S-100 protein was identified within this glandular element. Adequate material for ultrastructural study was available in five cases; all showed the presence of flattened cells located between the basement membrane and secretory epithelial cells, which had features typical for myoepithelial differentiation. Although the prostate gland does not normally contain myoepithelial cells, we have documented their consistent presence in this unusual lesion; we believe these cells arise by a metaplastic process from the prostatic basal cells.

Topics: Acid Phosphatase; Actins; Aged; Aged, 80 and over; Antigens, Neoplasm; Cell Differentiation; Epithelium; Humans; Immunohistochemistry; Keratins; Male; Microscopy, Electron; Middle Aged; Muscles; Prostate; Prostate-Specific Antigen; Prostatic Diseases; S100 Proteins; Sclerosis; Vimentin

The basal cell layer (BCL) is believed to be absent in malignant but present in nonmalignant epithelial lesions of the prostate. Using the avidin-biotin-peroxidase complex (ABC) immunoperoxidase method, we examined the value of the monoclonal antibody cocktail MA-903, which stains selectively the prostatic BCL layer, in the distinction between benign and malignant epithelial lesions of the prostate. We immunostained histologic sections of 63 prostates, containing 235 morphologic appearances: normal prostate glands, 43; benign prostate hyperplasia (BPH), 59; basal cell hyperplasia (BCH), 24; adenosis, seven; prostatic intraductal neoplasia (PIN 1), 21; PIN 2, 25; PIN 3, 16; and cancer, 40. Some degree (continuous, continuous with focal disruption, and disrupted patterns) of basal cell staining was demonstrable in all normal and BPH, BCH, and PIN 1 lesions, but was absent in 39 of 40 cancers. However, not every gland in benign lesions stained positively. Further, two of 25 PIN 2 and six of 16 PIN 3 lesions failed to reveal BCL. Our results suggest that the presence or absence of BCL, predicated on cytokeratin MA-903 immunoreactivity, may be a useful indicator in the distinction between benign and malignant epithelial lesions of the prostate.

Topics: Antibodies, Monoclonal; Biopsy, Needle; Diagnosis, Differential; Epithelium; Humans; Immunohistochemistry; Keratins; Male; Prostate; Prostatectomy; Prostatic Diseases; Prostatic Neoplasms

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

Topics: Humans; Image Processing, Computer-Assisted; Immunohistochemistry; Keratins; Male; Prostate; Prostatic Diseases; Prostatic Hyperplasia; Prostatic Neoplasms

There are a number of benign, small-acinar lesions in the prostate gland that may be difficult to differentiate from small-acinar adenocarcinoma. An important diagnostic criterion in this differentiation is the loss of the basal layer in small-acinar adenocarcinoma and its preservation in benign conditions. A monoclonal antibody to high-molecular-weight cytokeratins (34 beta E12) has been shown to stain these basal cells preferentially. To assess the usefulness of this antibody in distinguishing benign from malignant small-acinar lesions, we examined 21 cases of small-acinar adenocarcinoma and 47 examples of benign lesions, which included atypical adenomatous hyperplasia, atrophy, post-sclerotic hyperplasia, basal cell hyperplasia, and fibroepithelial nodule. Positive staining with 34 beta E12 was seen in 13/13 cases of atypical adenomatous hyperplasia, although in some cases the staining was weak and focal. Positivity with 34 beta E12 was also demonstrated in all other benign lesions studied. All 21 cases of small-acinar adenocarcinoma showed no reactivity with 34 beta E12. The results suggest that 34 beta E12 is of value in distinguishing between well-differentiated, small-acinar prostatic adenocarcinoma and its mimics. However, care is needed in interpretation of staining in formalin-fixed material due to the variable reactivity, particularly in cases of atypical adenomatous hyperplasia.

Topics: Adenocarcinoma; Adenoma; Antibodies, Monoclonal; Atrophy; Diagnosis, Differential; Evaluation Studies as Topic; Humans; Hyperplasia; Immunoenzyme Techniques; Keratins; Male; Molecular Weight; Prostate; Prostatic Diseases; Prostatic Neoplasms; Staining and Labeling

Topics: Autoantibodies; Connective Tissue Diseases; Humans; Keratins; Male; Prostatic Diseases