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Query: UMLS:C0007112 (prostatic adenocarcinoma)
 2,574 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recent clinicopathologic studies have shown that many prostatic adenocarcinomas express focal neuroendocrine differentiation and that neuroendocrine differentiation is most apparent in advanced anaplastic tumors. While studying growth-regulatory signal transduction events in human prostate carcinoma cell lines, we found that in two of four cell lines, the androgen-sensitive line LNCaP and the highly metastatic androgen-independent line PC-3-M, elevation of cAMP through addition of cAMP analogues or phosphodiesterase inhibitors induced a markedly neuronal morphology. Also in LNCaP cells ultrastructural analysis showed that cAMP induced the appearance of neurosecretory cell-like dense-core granules. Phenotypic analysis of untreated LNCaP and PC-3-M cells showed that both cell lines express markers of the neural crest including S-100, chromogranin A, pp60c-src, and neuron-specific enolase as well as the epithelial marker KS1/4 and stage-specific embryonic antigen 4. In PC-3-M cells, cAMP markedly elevated neuron-specific enolase protein and caused an increase in the specific activity of the neuroendocrine marker pp60c-src, and in both cell lines expression of KS1/4 and stage-specific embryonic antigen 4 was down-regulated. In addition to effects on lineage markers, cAMP treatment induced G1 synchronization, growth arrest, and loss of clonogenicity, indicating terminal differentiation. Our data provide direct evidence of plasticity in the lineage commitment of adenocarcinoma of the prostate. We have shown that cell-permeant cAMP analogues can induce terminal differentiation, suggesting that hydrolysis-resistant cyclic nucleotides may present an additional approach to the treatment of advanced prostate cancer.
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PMID:Terminal neuroendocrine differentiation of human prostate carcinoma cells in response to increased intracellular cyclic AMP. 820 89

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.
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PMID:Clinical implication of neuroendocrine differentiation in prostatic adenocarcinomas. 854 Jan 55

We describe the clinical and pathological findings in two Japanese men with small cell carcinoma of the prostate; case 1 was 58 years old and case 2 was 24 years old. Case 1 was initially diagnosed as a poorly differentiated adenocarcinoma of the prostate, stage D2, with marked elevation of serum neuron-specific enolase (NSE), carcinoembryonic antigen (CEA), and CA 19-9 levels. The patient had undergone castration and systemic chemotherapy. After three courses of chemotherapy, tumour markers were normalized. However, 6 months later serum levels of tumour markers again rose, and biopsy of the prostate revealed a small cell carcinoma component in the adenocarcinoma of the prostate and benign prostate hypertrophy. The patient was again treated with systemic chemotherapy but died within 1 year after relapse. In case 2, the patient presented with initial symptoms of lumbago and dysuria, and an enlarged prostate was radiologically diagnosed. Shortly after admission he developed ileus, and an exploratory laparotomy revealed a large tumour arising from the prostate and invading the peritoneal cavity. This tumour was pathologically diagnosed as a small cell carcinoma. The patient died shortly thereafter without responding to chemotherapy. Immunohistological evaluation was done using a panel of antibodies against NSE, chromogranin A, CEA, CA 19-9, prostatic acid phosphatase (PAP), prostate-specific antigen (PSA), leukocyte common antigen (LCA), epithelial membrane antigen (EMA), adrenocorticotropic hormone (ACTH), calcitonin, serotonin, gastrin, vasoactive intestinal peptide (VIP), and glucagon. CEA was intensely positive in the tumour lesions from case 1, and NSE and ACTH were focally positive, and calcitonin, serotonin, CA 19-9, and PSA were weakly positive only in several cells in the tumour lesions from case 1. In the tumour lesion from case 2, NSE was intensely positive, and chromogranin A was weakly positive. These findings support the neuroendocrine nature of this neoplasm.
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PMID:Two cases of small cell carcinoma of the prostate. 900 36

Neuroendocrine (NE) differentiation of prostatic adenocarcinomas has received increasing attention in recent years as a result of possible implications on prognosis and therapy. The incidence of NE cells in tumors has been reported from 10% up to 100%. Several studies have shown chromogranin A (CgA) to be the most reliable serum marker of NE differentiation. We have followed 22 patients with prostatic adenocarcinoma over a 2-year period. The patients underwent a palliative transurethral resection of the prostate (TURP) because of urinary outflow obstruction. The prostatic tissue specimens were stained immunohistochemically using antibodies against CgA, chromogranin B (CgB), neuron-specific enolase (NSE), thyroid-stimulating hormone (TSH), serotonin, and somatostatin. In addition, each specimen was stained with hematoxylin & eosin (H & E), and saffran for tumor grading. Blood samples were taken preoperatively and after 1, 3, 6, and 24 months. The serum values of CgA, CgB, pancreastatin (Pst), NSE, and prostate-specific antigen (PSA) were determined from each sample. Carcinomas with groups of CgA-positive cells had higher serum levels of CgA compared to carcinomas with no or only scattered CgA-positive NE cells. During the 2-year period, there were no statistical significant variations in serum levels of CgA, NSE, Pst, and PSA. However, there was a significant increase in serum levels of CgB during the same period, P = 0.002, possibly due to an increase in number of NE cells in tumor or to a relative increase in production of CgB in the NE cells.
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PMID:Use of neuroendocrine serum markers in the follow-up of patients with cancer of the prostate. 914 Jan 24

Neuroendocrine (NE) cells occur as scattered foci within prostatic adenocarcinoma, similar to their distribution within ductal epithelial cells of the normal prostate. However, the density of NE cells is often greater in prostate carcinomas than in normal tissue, and the frequency of NE cells correlates with tumor grade, loss of androgen sensitivity, autocrine/paracrine activity, and poor prognosis. Although NE cells are nonmitotic, proliferating cells are found in direct proximity to them, suggesting that NE cells provide paracrine stimuli for surrounding carcinoma cells. In vitro, differentiation of the LNCaP and PC3M prostatic tumor cell lines to a NE phenotype can be induced by dibutyryl cyclic AMP (cAMP), suggesting that physiological agents that increase intracellular concentrations of cAMP might regulate NE differentiation in vivo. Indeed, we demonstrate in this report that LNCaP cells acquire NE characteristics in response to treatment with physiological and pharmacological agents that elevate intracellular cAMP, agents such as epinephrine, isoproterenol, forskolin, and dibutyryl cAMP. The androgen-independent LNCaP-derived cell line C4-2 also responded to these agents, indicating that cells representing later stages of tumor progression are also capable of differentiation. The NE phenotype in this study was monitored by the appearance of dense core granules in the cytoplasm, the extension of neuron-like processes, loss of mitogenic activity, and expression of the NE markers neuron-specific enolase, parathyroid hormone-related peptide, neurotensin, serotonin, and chromogranin A. However, contrary to previous reports, we observed rapid loss of the NE phenotype in both LNCaP and C4-2 cells upon withdrawal of inducing agents. Withdrawal also resulted in a rapid, dramatic increase in tyrosine kinase and mitogen-activated protein kinase activities, suggesting that activation of these intracellular signaling enzymes may be important for reentry into the cell cycle. Together, these results indicate that chronic cAMP-mediated signaling is required to block proliferation of prostate tumor cells and to induce NE differentiation.
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PMID:Acquisition of neuroendocrine characteristics by prostate tumor cells is reversible: implications for prostate cancer progression. 1044 1

We report a case with an initial diagnosis of adenocarcinoma of the prostate in whom Cushing's syndrome developed. The disease did not respond to estrogen treatment and the patient died of severe septicemia. Histopathologic examination of the autopsy specimens revealed a small cell carcinoma intermingled with a moderately differentiated adenocarcinoma in the prostate and widespread metastases of small cell carcinoma. Immunoreactivity for neuroendocrine differentiation was found only in the small cell carcinoma. Determination of different tumor markers in plasma samples showed markedly elevated levels of prostate-specific antigen as well as carcinoembryonic antigen prior to treatment, with no significant changes after treatment. The concentration of the neuroendocrine marker chromogranin A was initially within the normal range, but increased during estrogen treatment, whilst neuron-specific enolase was moderately elevated throughout the observation period.
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PMID:Cushing's syndrome in prostate cancer. An aggressive course of prostatic malignancy. 1059 2

We report an unusual variant of prostatic adenocarcinoma with marked endocrine differentiation (mixed endocrine-exocrine adenocarcinoma). Endocrine cells accounted for 60% of the tumour cells, were positive with silver impregnation and for chromogranin A, synaptophysin, and neuron-specific enolase, and coexpressed the exocrine antigens prostatic acid phosphatase and prostatic-specific antigen. Most of the endocrine cells were basophilic with haematoxylin-eosin and proved immunoreactive for alpha subunit of human chorionic gonadotropin and follicle-stimulating hormone. The remaining endocrine cells were represented by eosinophilic cells positive for serotonin, and by calcitonin and serotonin-immunoreactive cells not identifiable in haematoxylin-eosin-stained sections. On ultrastructural analysis, two types of endocrine cells were identified. The most frequent cell type showed abundant cytoplasmic round, electron-dense neurosecretory granules, either small (212+/-44 nm) or large (471+/-114 nm), resembling those of gonadotropic pituitary cells. The second type of endocrine cells contained irregular electron-dense granules similar to those of serotonin-storing enterochromaffin cells.
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PMID:Unusual prostatic adenocarcinoma with endocrine basophilic FSH-immunoreactive cells. 1091 80

We report two cases of combined small-cell carcinoma (SCC) and adenocarcinoma of prostate. Case 1 was a 76-year-old man with loss of appetite and body weight and neck lymphadenopathies. Whole body computed tomography (CT) revealed prostatic swelling, pancreatic mass, para-aortic lymphadenopathies, and multiple lung nodules. Elevation of tumor markers (prostate specific antigen [PSA, 1,760 ng/ml] and neuron-specific enolase [NSE, 88 ng/ml]) was noted. Needle biopsy of the prostate demonstrated both SCC and adenocarcinoma. Only within the part of SCC, were neuroendocrine (NE) markers (chromogranin A [CgA], NCAM, and synaptophysin [SNP]) expressed. Maximum androgen blockade (MAB) resulted in a decrease of PSA (5.13 ng/ml) but an increase of NSE (810 ng/ml). Cytotoxic chemotherapy was not possible because of his poor performance state and renal dysfunction. The patient died three months after the diagnosis. Case 2 was a 69-year-old male with dysuria. The symptom and elevated serum PSA (23.1 ng/ml) prompted prostatic needle biopsy, which demonstrated combined SCC/adenocarcinoma. NE markers (CgA and SNP) were weakly expressed in the part of SCC. Serum NSE was 6.9 ng/ml. After MAB, serum PSA dropped to the normal range (0.192 ng/ml) and the effect of MAB was judged as complete response (CR). The patient has been alive for 15 months with no signs of relapse. Treatment of combined SCC and adenocarcinoma of prostate poses a dilemma. In Case 1, MAB was effective for adenocarcinoma but not for SCC. The opposite situation would be expected with systemic chemotherapy. However, the histologically similar Case 2 achieved CR with MAB alone. Much remains to be elucidated to better manage combined SCC/adenocarcinoma of prostate.
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PMID:[Combined small-cell carcinoma/adenocarcinoma of prostate: report of two cases]. 1770 84

A case of neuroendocrine (NE) differentiated prostate cancer is reported herein, which was progressed with NE differentiation during hormonal treatment in adenocarcinoma of the prostate. A 65-year-old man was admitted to our department with increased serum prostate specific antigen (PSA) (150 ng/ml). A prostate biopsy was performed and histological examinations indicated poorly differentiated adenocarcinoma with a Gleason score of 5 + 4 = 9. Further examinations showed metastases to systemic bones. The clinical stage was T3bN0M1b and hormonal therapy using leuprorelin was started. Eighteen months after hormonal therapy, the serum PSA level declined to 1.702 ng/ml. He subsequently experienced edema in his legs. Computed tomography (CT) demonstrated enlargement of the prostate and swelling of multiple pelvic lymph nodes. Immunohistochemical examination of a re-biopsy specimen revealed a neuroendocrine carcinoma. The neuron-specific enolase (NSE) level was 50.9 ng/ml. The treatment measure was changed from hormonal therapy to combination chemotherapy comprising cisplatin (CDDP) and irinotecan (CPT-11). Pelvic radiotherapy (50 Gy) was then performed. Two courses of the chemotherapy resulted in a great reduction of the tumor volume. However, he had liver metastases 3 months later. His condition worsened rapidly and he died at 8 months after definite diagnosis.
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PMID:[Neuroendocrine differentiation in adenocarcinoma of the prostate during hormonal treatment : a case report]. 2010 11

In the present study, we describe an 80-year-old patient who developed prostatic small cell carcinoma (SCC) following high-dose-rate brachytherapy (HDR-BT) for low-risk prostatic adenocarcinoma. The patient received one implant of Ir-192 and 7 fractions of 6.5 Gy within 3.5 days, for a total prescribed dose of 45.5 Gy. A total of 27 months after HDR-BT, the patient complained of difficulty in urinating. His serum prostate-specific antigen (PSA) levels were 3.2 ng/ml. Systemic examination revealed an enlargement of the prostate, urethral stenosis, pelvic lymph node swelling and multiple lung and bone lesions. His serum neuron-specific enolase (NSE) levels were elevated to 120 ng/ml. A prostate needle biopsy was performed for pathological examination. Histologically, there were tumor cells with hyperchromatic nuclei and scant cytoplasm showing a solid or trabecular growth pattern. Immunohistochemically, they were positive for AE1/AE3, CD56 and synaptophysin, and negative for PSA, PAP and CD57. These findings are consistent with SCC of the prostate. A review of the prostate needle biopsy specimen prior to HDR-BT did not reveal any tumor cells positive for chromogranin A, nor synaptophysin. The final diagnosis was SCC of the prostate with local progression, with lung, lymph node and bone metastases. Three cycles of etoposide/cisplatin (EP) were administered. A greater than 50% decrease in the serum NSE levels was observed. However, there was no objective response. Due to the deterioration of the patient's general condition, EP was discontinued. One month later, his serum NSE showed a rapid increase to 210 ng/ml with aggressive local progression and the patient succumbed to the disease 5.5 months after the start of EP therapy.
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PMID:Small cell carcinoma of the prostate after high-dose-rate brachytherapy for low-risk prostatic adenocarcinoma. 2325 93


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