acid-phosphatase and Carcinoma--Small-Cell

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

The aim of this study was to assess the dynamics of osteoclast migration and the degradation of unmineralized extracellular matrix in an osteolytic metastasis by examining a well-standardized lung cancer metastasis model of nude mice. SBC-5 human lung small carcinoma cells were injected into the left cardiac ventricle of 6-week-old BALB/c nu/nu mice under anesthesia. At 25-30 days after injection, the animals were sacrificed and their femora and/or tibiae were removed for histochemical analyses. Metastatic lesions were shown to occupy a considerable area extending from the metaphyses to the bone marrow region. Tartrate resistant acid phosphatase (TRAPase)-positive osteoclasts were found in association with an alkaline phosphatase (ALPase)-positive osteoblastic layer lining the bone surface, but could also be localized in the ALPase-negative stromal tissues that border the tumor nodules. These stromal tissues were markedly positive for osteopontin, and contained a significant number of TRAPase-positive osteoclasts expressing immunoreactivity for CD44. We thus speculated that, mediating its affinity for CD44, osteopontin may serve to facilitate osteoclastic migration after their formation associated with ALPase-positive osteoblasts. We next examined the localization of cathepsin K and matrix metallo-proteinase-9 (MMP-9) in osteoclasts. Osteoclasts adjacent to the bone surfaces were positive for both proteins, whereas those in the stromal tissues in the tumor nests showed only MMP-9 immunoreactivity. Immunoelectron microscopy disclosed the presence of MMP-9 in the Golgi apparatus and in vesicular structures at the baso-lateral cytoplasmic region of the osteoclasts found in the stromal tissue. MMP-9-positive vesicular structures also contained fragmented extracellular materials. Thus, osteoclasts appear to either select an optimized function, namely secreting proteolytic enzymes from ruffled borders during bone resorption, or recognize the surrounding extracellular matrix by mediating osteopontin/CD44 interaction, and internalize the extracellular matrices. Microsc.

Topics: Acid Phosphatase; Animals; Bone Neoplasms; Carcinoma, Small Cell; Cathepsin K; Cathepsins; Cytoplasmic Vesicles; Disease Models, Animal; Extracellular Matrix; Femur; Golgi Apparatus; Humans; Hyaluronan Receptors; Immunohistochemistry; Male; Matrix Metalloproteinase 9; Mice; Mice, Inbred BALB C; Mice, Nude; Microscopy, Immunoelectron; Osteoclasts; Osteolysis; Osteopontin; Sialoglycoproteins; Tibia

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

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

Numerous ectopic hormones and markers have been described in small cell carcinoma of the lung as well as in extrapulmonary small cell carcinomas. The authors report a case of a patient with metastatic small cell carcinoma of unknown primary who had very high prostatic acid phosphatase (PAP) and prostatic specific antigen (PSA) levels. Results of multiple prostate examinations, as well as blind biopsies, were normal. His course was significantly longer than that of the usual patient with extensive small cell carcinoma. At autopsy the prostate showed only mild benign prostatic hypertrophy. There are no previous reports in the literature of abnormal prostate markers in small cell carcinomas. Physicians should be aware of the increasing complexity and the unusual biologic markers associated with neuroendocrine carcinomas. In some of these cases, the tumors ability to produce an ectopic product may portend an improved prognosis.

Topics: Acid Phosphatase; Aged; Antigens, Neoplasm; Biomarkers, Tumor; Carcinoma, Small Cell; Choristoma; Female; Humans; Kidney Neoplasms; Male; Neoplasms, Unknown Primary; Prostate; Prostate-Specific Antigen

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

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

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

Small cell carcinomas of the prostate are rare. A few reported cases have manifested morphologic and functional neuroendocrine characteristics, and it has been suggested that these tumors are derived from the argentaffinic/argyrophilic cells normally present in the prostate. The authors have recently studied three cases of primary prostatic small cell carcinoma in which the small cell component developed during the course of progression of "regular" prostatic adenocarcinoma, and reflected a terminal aggressive phase of the disease. Immunoperoxidase staining for prostate-specific acid phosphatase (PSAP) showed positivity in the adenocarcinoma but absence in the small cell component of each tumor. The association of small cell carcinoma with prostatic adenocarcinoma indicates that in considering the histogenesis of prostatic small cell carcinoma, a specific neuroendocrine cell of origin need not be implicated.

Topics: Acid Phosphatase; Adenocarcinoma; Adrenocorticotropic Hormone; Aged; Carcinoma, Small Cell; Histocytochemistry; Humans; Immunoenzyme Techniques; Male; Prostatic Neoplasms

Purified plasma membranes were obtained from five transplantable human tumors, a grade IV astrocytoma, an oat cell carcinoma, and three melanomas. Plasma membrane fractions were isolated from tumor homogenates by differential and discontinuous sucrose gradient centrifugation. Determination of enzyme activities indicated that the plasma membranes were enriched 10- to 20-fold with respect to 5'-nucleotidase, nicotinamide adenine dinucleotide glycohydrolase, Mg2+-activated nucleoside triphosphatase, and sialic acid. Specific activities of nearly all the enzymes varied with the individual tumors, even among tumors of the same type, i.e., the melanomas. Electron micrographs of the plasma membrane fractions showed smooth single-membrane vesicles with slight contamination by lysosomes. Therefore, these membranes are suitable for comparative biochemical studies and for the preparation of tumor-specific monoclonal antibodies. Plasma membranes from all five tumors contained very high Mg2+-adenosine triphosphatase (ATPase) activities. The Na+-K+-ATPase was a minor component of the total ATPase of these membranes (less than 30%). The major component was an ATPase exhibiting similar activity toward several nucleoside triphosphates. The activity of such a nucleoside triphosphatase has been correlated with tumorigenicity in cultured liver epithelial cells. The nucleoside triphosphatase of the plasma membranes of astrocytoma and oat cell carcinoma was stimulated from 50 to 1005 by concanavalin A, whereas ATPase of the melanoma plasma membranes was not or only slightly stimulated. The different response to concanavalin A could be due to differences in the ATPase molecules of the individual tumors or to the different environment of the ATPase.

Topics: Acid Phosphatase; Adenosine Triphosphatases; Animals; Ca(2+) Mg(2+)-ATPase; Carcinoma, Small Cell; Cell Membrane; Glioblastoma; Humans; Melanoma; Mice; Mice, Nude; NAD+ Nucleosidase; NADH Dehydrogenase; Neoplasm Transplantation; Neoplasms, Experimental; Nucleotidases; Sialic Acids; Transplantation, Heterologous