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

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

Androgen, acting via the androgen receptor (AR), is associated with the development and progression of prostate cancer. Anti-androgen therapy is widely used to manage prostate cancer. However, the conversion of the tumor from a hormone-sensitive to a hormone-insensitive status causes such therapy to fail. Several mechanisms have now been put forward for this conversion, including neuroendocrine (NE) differentiation of the tumor cells. In this study, we evaluated the prognostic significance of tumor-cell proliferation activity, NE differentiation and AR expression. Formalin-fixed, paraffin-embedded sections were prepared from 42 patients with adenocarcinoma of the prostate. Using antibodies to AR, the Ki-67 antigen (MIB-1), chromogranin A and synaptophysin, immunohistochemical expression of AR, tumor proliferation activity and NE differentiation were analyzed. Our study revealed that AR expression was significantly lower in adenocarcinoma (52.2 +/- 27.1%) than in non-tumorous prostate tissue (68.3 +/- 18.3%; P < 0.001). NE differentiation was found in 50% of the tumors, which was correlated with the Gleason score (P < 0.05). An univariate analysis revealed a significant correlation between progression-free survival with both AR expression (P < 0.01) and proliferation activity (P < 0.001). NE differentiation was not a prognostic factor in this study.
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PMID:Prognostic significance of neuroendocrine differentiation, proliferation activity and androgen receptor expression in prostate cancer. 1142 7

Neuroendocrine (NE) differentiation frequently occurs in common prostatic malignancies and has attracted increasing attention in contemporary prostate cancer research. This particular phenotype, however, usually escapes pathological and clinical detection in routine practice. The present review focuses on the biological properties of NE tumor cells that make them resistant to androgen deprivation and radiation therapy. NE cells produce a number of hormonal growth factors (e.g., serotonin) that may act through endocrine, paracrine, and autocrine mechanisms. Morphogenetic studies have identified intermediate phenotypes between the three basic cell types of the prostatic epithelium indicating their common origin from stem cells located in the basal cell layer. Virtually all prostatic adenocarcinomas show NE differentiation as defined by the most commonly used endocrine marker chromogranin A. Clinical studies suggest that the extent of NE differentiation increases with tumor progression and the development of androgen insensitivity. NE differentiation exclusively occurs in the G0 phase of the cell cycle in which tumor cells are usually resistant to radiation therapy and cytotoxic drugs. In addition, NE tumor cells also escape programmed cell death. Even under androgen deprivation, only 0.16% of NE tumor cells show apoptotic activity. This indicates that the vast majority of NE tumor cells represent an immortal cell population in prostate cancer. Although NE tumor cells do not proliferate, they produce a number of NE growth factors with mitogenic properties that maintain cell proliferation in adjacent (exocrine) tumor cells through a paracrine mechanism. NE tumor cells consistently lack the androgen receptor and are androgen insensitive in all stages of the disease. They derive through a process of intermediate differentiation from exocrine tumor cells, the most prevalent phenotype in common prostatic adenocarcinoma. Elevated serum levels of chromogranin A in prostate cancer patients correlate with poor prognosis and are scarcely influenced by either androgen deprivation or chemotherapy. Looking for NE differentiation is recommended in the pathological and clinical evaluation of prostate cancer patients for whom radiation and androgen deprivation are therapeutic options.
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PMID:[Neuroendocrine differentiation in prostate cancer. An unrecognized and therapy-resistant phenotype]. 1504 55

Neuroendocrine (NE) differentiation in prostate cancer is typically detected by immunohistochemistry as single cells in conventional adenocarcinoma. Prostatic NE tumors, such as carcinoid or small cell carcinoma, are rare and large cell NE carcinoma (LCNEC) is described only in case reports. We identified 7 cases of LCNEC and compiled their clinicopathologic characteristics. In 6 cases, there was a history of adenocarcinoma treated with hormone therapy for a mean of 2.4 years (range: 2 to 3 y). The remaining case was de novo LCNEC. LCNEC was incidentally diagnosed in palliative transurethral resection specimens in 5 cases. The mean patient age at diagnosis with LCNEC was 67 years (range: 43 to 81 y). LCNEC comprised solid sheets and ribbons of cells with abundant pale to amphophilic cytoplasm, large nuclei with coarse chromatin and prominent nucleoli along with brisk mitotic activity and foci of necrosis. In 6 cases, there were foci of admixed adenocarcinoma, 4 of which showed hormone therapy effects. LCNEC was strongly positive for CD56, CD57, chromogranin A, synaptophysin, and P504S/alpha methylacyl CoA racemase. There was strong bcl-2 overexpression, expression of MIB1, and p53 in >50% of nuclei, focally positive staining for prostate specific antigen and prostatic acid phosphatase and negative androgen receptor staining. Follow-up was available for 6 patients, all of who died with metastatic disease at mean of 7 months (range: 3 to 12 mo) after platinum-based chemotherapy. LCNEC of prostate is a distinct clinicopathologic entity that typically manifests after long-term hormonal therapy for prostatic adenocarcinoma and likely arises through clonal progression under the selection pressure of therapy.
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PMID:Large cell neuroendocrine carcinoma of prostate: a clinicopathologic summary of 7 cases of a rare manifestation of advanced prostate cancer. 1672 45

A 74-yr-old man with prostatic adenocarcinoma underwent magnetic resonance 1H-spectroscopic imaging (1H-MRSI) of the prostate. Based on the results, he was treated with combination therapy using complete androgen blockade (leuprorelin acetate 3.75 mg every 4 wk plus bicalutamide 50 mg daily) and a somatostatin analogue (lanreotide acetate 60 mg every 4 wk). Serum prostate-specific antigen and chromogranin A levels steadily decreased over a 12-mo follow-up period, at which time the patient is alive without disease progression and with a complete objective and symptomatic response.
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PMID:Complete response to the combination therapy with androgen blockade and somatostatin analogue in a patient with advanced prostate cancer: magnetic resonance imaging with 1H-spectroscopy. 1731 66

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

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

Prostate adenocarcinoma is frequently diagnosed on needle biopsies in early, organ-confined stages. New prognostic factors would help identifying at this stage patients at risk for unfavorable evolution, that would benefit from alternate therapy. This study aims to find correlations between the extent of neurocrine differentiation (NED), a feature commonly seen in prostate carcinoma, and known factors of disease evolution such as histological grade, malignant cell proliferation and serum PSA levels. Immunohistochemistry for choromogranin A and neuron-specific enaolase (NSE) was used to calculate expression scores in order to asses the extent of NED in prostate biopsies. Tumour proliferative activity was estimated by calculating percentages of Ki-67 immunoreactive cell nuclei. Results show that the presence of numerous clusters of chromogranin A positive cells is a feature that differentiate tumours with Gleason score 9 from those with a score of 6. Also, the same extended neuroendocrine differentiation is associated with high tumour proliferative activity. Multinomial regression analysis showed that high Ki indices, serum PSA values and NSE scores are predictive for moderately and poorly differentiated prostatic adenocarcinoma.
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PMID:Neuroendocrine differentiation in prostate adenocarcinoma biopsies and its correlation to histological grading. 2477 25

The term aggressive variant prostate cancer (AVPCa) refers to androgen receptor (AR)-independent anaplastic forms of prostate cancer (PCa), clinically characterized by a rapidly progressive disease course. This involves hormone refractoriness and metastasis in visceral sites. Morphologically, AVPCa is made up of solid sheets of cells devoid of pleomorphism, with round and enlarged nuclei with prominent nucleoli and slightly basophilic cytoplasm. The cells do not show the typical architectural features of prostatic adenocarcinoma and mimic the undifferentiated carcinoma of other organs and locations. The final diagnosis is based on the immunohistochemical expression of markers usually seen in the prostate, such as prostate-specific membrane antigen (PSMA). A subset of AVPCa can also express neuroendocrine (NE) markers such as chromogranin A, synaptophysin and CD56. This letter subset represents an intermediate part of the spectrum of NE tumors which ranges from small cell to large cell carcinoma. All such tumors can develop following potent androgen receptor pathway inhibition. This means that castration-resistant prostate cancer (CRPCa) transdifferentiates and becomes a treatment-related NE PCa in a clonally divergent manner. The tumors that do not show NE differentiation might harbor somatic and/or germline alterations in the DNA repair pathway. The identification of these subtypes has direct clinical relevance with regard to the potential benefit of platinum-based chemotherapy, poly (ADP-ribose) polymerase inhibitors and likely further therapies.
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PMID:Morphologic, Molecular and Clinical Features of Aggressive Variant Prostate Cancer. 3234 31


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