Differentiation In Prostatic Carcinoma Research Articles

The value of STEAP1, C-myc and P63 Immuno-expression in differentiation of prostatic carcinoma from its mimickers

The value of STEAP1, C-myc and P63 Immuno-expression in differentiation of prostatic carcinoma from its mimickers

Neuroendocrine differentiation of prostatic adenocarcinoma – an important cause for castration-resistant disease recurrence

Abstract Background Neuroendocrine differentiation of prostatic carcinoma is a rare entity associated with metastatic castration-resistant disease. Among useful biomarkers of neuroendocrine differentiation, chromogranin A, serotonin, synaptophysin and neuron-specific enolase stand out, while total prostate-specific antigen (PSA) levels are often low or undetectable. Case presentation We report a case of prostatic adenocarcinoma recurrence after a 6-year disease-free follow-up, in which increased serum chromogranin A levels and undetectable total PSA provided a prompt indication of neuroendocrine transformation, confirmed through immunohistochemical evaluation. Conclusions Neuroendocrine differentiation is a relevant cause of prostatic adenocarcinoma recurrence, and awareness of this entity is crucial due to its underdiagnosis and adverse prognosis.

Cyclin D1 Loss Distinguishes Prostatic Small-Cell Carcinoma from Most Prostatic Adenocarcinomas.

Small-cell neuroendocrine differentiation in prostatic carcinoma is an increasingly common resistance mechanism to potent androgen deprivation therapy (ADT), but can be difficult to identify morphologically. We investigated whether cyclin D1 and p16 expression can inform on Rb functional status and distinguish small-cell carcinoma from adenocarcinoma. We used gene expression data and immunohistochemistry to examine cyclin D1 and p16 levels in patient-derived xenografts (PDX), and prostatic small-cell carcinoma and adenocarcinoma specimens. Using PDX, we show proof-of-concept that a high ratio of p16 to cyclin D1 gene expression reflects underlying Rb functional loss and distinguishes morphologically identified small-cell carcinoma from prostatic adenocarcinoma in patient specimens (n = 13 and 9, respectively). At the protein level, cyclin D1, but not p16, was useful to distinguish small-cell carcinoma from adenocarcinoma. Overall, 88% (36/41) of small-cell carcinomas showed cyclin D1 loss by immunostaining compared with 2% (2/94) of Gleason score 7-10 primary adenocarcinomas at radical prostatectomy, 9% (4/44) of Gleason score 9-10 primary adenocarcinomas at needle biopsy, and 7% (8/115) of individual metastases from 39 patients at autopsy. Though rare adenocarcinomas showed cyclin D1 loss, many of these were associated with clinical features of small-cell carcinoma, and in a cohort of men treated with adjuvant ADT who developed metastasis, lower cyclin D1 gene expression was associated with more rapid onset of metastasis and death. Cyclin D1 loss identifies prostate tumors with small-cell differentiation and may identify a small subset of adenocarcinomas with poor prognosis. Clin Cancer Res; 21(24); 5619-29. ©2015 AACR.

Incidence of high chromogranin A serum levels in patients with non metastatic prostate adenocarcinoma

BackgroundChromograninA in prostate carcinoma (PC) indicate NE differentiation. This tumour is more aggressive and resistant to hormone therapy.Patients and methodsWe analyzed the incidence of pre-operative ChromograninA serum levels in non metastatic PC patients. Serum PSA and ChromograninA were analyzed before treatment. Clinicopathological parameters were evaluated in relation to serum ChromograninA. 486 patients were enrolled.ResultsWe found 352 pT2 and 134 pT3. 21 patients were N+. 278 patients had Gleason score levels <7; 173 patients had levels = 7 (122 were 3+4 and 51 4+3); and 35 patients with levels >7. Median PSA pre-operative level was 7.61 ng/ml. PSA was significantly associated with pT stage (pT2 with PSA abnormal 23.6% vs pT3 48.5%, p < 0.0001) and with a Gleason score (PSA abnormal 60% in the Gleason score was >7 vs 29.5% in the Gleason score = 7 vs 27.3% in the Gleason score <7, p < 0.0001). In 114 patients pre-operative ChromograninA levels were elevated (23.5%). Serum ChromograninA levels had no significant association with PSA (p = 0.44) and pT stage (p = 0.89). abnormal ChromograninA levels increased from a Gleason score of <7 (25.5%) to >7 (31.4%) (p = 0.12). The serum ChromograninA levels in the two groups of patients were subdivided before and after 2005 on the basis of different used assays, showing no correlation with serum ChromograninA and other parameters.ConclusionsThis study showed that ChromograninA levels correlated to NE differentiation and possible aggressiveness of PC. Pre-operative circulating ChromograninA could complement PSA in selecting more aggressive PC cases, particularly in the presence of a higher Gleason score. Complementary information is provided by the absence of a correlation between serum ChromograninA and PSA levels.

Weiterentwicklung der PET und des PET/CT beim Prostatakarzinom

Functional imaging of prostate carcinoma was examined with the metabolic substrates 2-(18)F-fluorodeoxyglucose, (11)C-methionine, (18)F-fluorodihydrotestosterone, (11)C-acetate and (11)C/(18)F-choline. Based on upregulated enzymes of phospholipid metabolism in prostate carcinoma, (11)C/(18)F-choline is preferentially incorporated into phosphatidylcholine of membrane lipids of prostate cancer cells. PET allows sensitive detection of the (11)C/(18)F-choline signal and PET/CT fusion imaging enables intraprostatic signal localisation. Most published studies report a high detection rate of prostate carcinoma with (11)C/(18)F-choline PET/CT. Differentiation of prostate carcinoma from benign hyperplasia and from focal chronic prostatitis may be difficult; acute prostatitis accumulates (11)C/(18)F-choline with an intensity comparable to prostate carcinoma.

Influence of neuroendocrine tumor cells on proliferation in prostatic carcinoma

Neuroendocrine (NE) tumor cells in prostatic carcinoma (PCa) may influence tumor proliferation by a paracrine stimulus. The role of NE tumor cells is discussed controversially. This study investigates the influence of NE tumor differentiation on proliferation in PCa. Neuroendocrine differentiation, Ki-67, and Polo-like kinase 1 were studied immunohistochemically in 73 consecutive prostatectomies. Polo-like kinase 1 (PLK1) expression was also studied by Western and Northern blot analysis. Tumors were classified as high NE (HNE) and low NE differentiated (LNE), and depending on the growth pattern, with solitary and clusters of NE tumor cells. Low NE differentiated tumors were defined as less than 30 and HNE as 30 or more NE tumor cells per hot spot. Patients were followed by serum prostate-specific antigen (PSA) analysis. Neuroendocrine differentiation was present at least focally in 70% of tumors; 57% were HNE and 43% LNE. Solitary NE tumor cells were more often found in low-grade PCa, whereas clusters of NE tumor cells were more frequent in high-grade PCa. PLK1 messenger RNA and protein as well as Ki-67 were overexpressed in tumor tissue compared with tumor-free tissue. A stronger proliferation as determined by Ki-67 and PLK1 expression was present in HNE tumors compared with LNE tumors and in tumors with clusters in contrast to tumors with solitary NE tumor cells. Analysis for PSA relapse-free survival showed an earlier progression in HNE than in LNE tumors and in PCa with clusters of NE tumor cells. A significant and clustered NE differentiation in PCa may lead to an increased proliferation and earlier tumor progression, whereas few and solitary NE tumor cells have no prognostic impact.

The influence of neuroendocrine differentiation on the growth and androgen receptor expression of prostate carcinoma cells

To study the paracrine effect of the neuroendocrine differentiation cells and its influence on androgen receptor expression of prostate carcinoma cells. Established an in vitro induced model of neuroendocrine differentiation of prostate carcinoma (LNCaP(NE), PC-3M(NE)), and investigate the proliferation effect of neuroendocrine phenotype cells (LNCaP(NE), PC-3M(NE)) on other non-neuroendocrine phenotype cells (LNCaP, PC-3M) by feeding non-neuroendocrine phenotype cells with the medium pre-incubated with induced neuroendocrine phenotype cells. It was also tested the regulation of androgen receptor mRNA and androgen receptor protein expression of LNCaP(NE) cells on LNCaP cells by reverse transcriptase polymerase chain reaction and Western Blot in the presence or absence of androgens. The medium pre-incubated with PC-3M(NE) cells could promote the proliferation of PC-3M cells. The medium pre-incubated with LNCaP(NE) cells could promote the proliferation of LNCaP cells, and reduce the expression of androgen receptor in the latter in the absence of androgens, but the negative results were observed in the presence of androgens. The neuroendocrine phenotype cells of prostate cancer can reduce the expression of androgen receptor in prostate cancer cells and promote them to proliferate by means of paracrine in the blockade of androgens.

Metastatic Carcinoid Tumor of the Prostate

No AccessJournal of UrologyCLINICAL UROLOGY: Case Reports1 Jun 2002Metastatic Carcinoid Tumor of the Prostate JENNIFER A. TASH, VICTOR REUTER, and PAUL RUSSO JENNIFER A. TASHJENNIFER A. TASH More articles by this author , VICTOR REUTERVICTOR REUTER More articles by this author , and PAUL RUSSOPAUL RUSSO More articles by this author View All Author Informationhttps://doi.org/10.1016/S0022-5347(05)65024-0AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail "Metastatic Carcinoid Tumor of the Prostate." The Journal of Urology, 167(6), pp. 2526–2527 References 1 : Diffuse carcinoid of prostate. Urology1981; 18: 407. Google Scholar 2 : Neuroendocrine cells of the prostate and neuroendocrine differentiation in prostatic carcinoma: a review of morphologic aspects. Urology1998; 51: 121. Google Scholar 3 : Gastrointestinal carcinoid tumors: current management strategies. Dis Colon Rectum1997; 40: 1101. Google Scholar 4 : Treatment of neuroendocrine carcinomas with combined etoposide and cisplatin. Evidence of major therapeutic activity in the anaplastic variants of these neoplasms. Cancer1991; 68: 227. Google Scholar 5 : Phase II trial of neoadjuvant estramustine and etoposide plus radical prostatectomy for locally advanced prostate cancer. Urology2001; 57: 281. Google Scholar From the James Buchanan Brady Urology Foundation, Department of Urology, The New York Presbyterian Hospital-Weill Medical College of Cornell University, and Departments of Pathology and Urology, Memorial Sloan-Kettering Cancer Center, New York, New York© 2002 by American Urological Association, Inc.FiguresReferencesRelatedDetails Volume 167Issue 6June 2002Page: 2526-2527 Advertisement Copyright & Permissions© 2002 by American Urological Association, Inc.Keywordsprostatic neoplasmsneoplasm metastasiscarcinoid tumorMetricsAuthor Information JENNIFER A. TASH More articles by this author VICTOR REUTER More articles by this author PAUL RUSSO More articles by this author Expand All Advertisement PDF downloadLoading ...

Neuropeptides bombesin and calcitonin induce resistance to etoposide induced apoptosis in prostate cancer cell lines.

Neuroendocrine differentiation in prostatic carcinoma has been related to regulation of proliferation and metastatic potential and correlated with prognosis. More than 80% of prostate carcinomas initially respond to androgen ablation, but most relapse, due to the heterogeneous presence of androgen-dependent and independent clones. The pathways of cellular proliferation and apoptosis are inexorably linked to minimize the occurrence of neoplasia, and disfunction of apoptosis is proposed as a pathogenic process in malignant tumors. Androgen-dependent prostatic cancer cells undergo apoptosis after androgen deprivation, but not androgen-independent ones due to a defect in the initiation step. Anyway, they retain the basic cellular machinery to undergo apoptosis. We suggest a possible role of neuroendocrine differentiation in the onset and regulation of apoptosis in prostatic neoplasia. LNCaP, PC-3 and DU 145 prostatic cancer cell lines were induced to undergo apoptosis after treatment with etoposide alone or plus androgen ablation. We tested the role of neuropeptides bombesin and calcitonin at modulating etoposide induced apoptosis. Etoposide-induced apoptosis in all cancer cell lines was achieved. In LNCaP androgen ablation was also required. Apoptosis is prevented in all three lines when bombesin was added. Calcitonin addition prevents apoptosis in PC-3, LNCaP and in an etoposide dose-dependent way in DU 145. Neuropeptides bombesin and calcitonin can modulate the apoptotic response of prostate cancer cells by inducing resistance to etoposide-induced apoptosis, suggesting that neuropeptides can be used as a target of therapeutical approach in prostatic carcinoma.

ELEVATED LEVELS OF SERUM SECRETONEURIN IN PATIENTS WITH THERAPY RESISTANT CARCINOMA OF THE PROSTATE

The majority of prostate cancers show some degree of neuroendocrine differentiation. It was previously demonstrated that chromogranin A, a constituent of large dense core vesicles of neuroendocrine cells, is frequently elevated in patients with metastatic prostate cancer. We evaluate the expression of secretoneurin, which is generated by proteolytic processing of secretogranin II (chromogranin C), in patients with prostate disease. Secretoneurin was measured in sera of 16 healthy men whose blood was drawn for prostate cancer screening (controls), and in 9 patients with prostatitis, 19 with benign prostate hyperplasia and 54 with prostate cancer detected by radioimmunoassay. Therapy resistant disease (clinical stage D3) was noted in 20 prostate cancer cases. Serum prostate specific antigen was measured in all patients and controls. In addition, chromogranin A, prostate acid phosphatase and interleukin-6 were determined in patients with D3 prostate cancer. Molecular properties of secretoneurin immunoreactivity were analyzed by gel filtration chromatography followed by radioimmunoassay. Mean secretoneurin was 58.9+/-8 fmol./ml. in patients with therapy resistant prostate cancer. Levels were significantly higher than those measured in sera from controls and patients with prostatitis, benign prostatic hyperplasia and pT2 or pT3 prostate cancer. There was a statistically significant correlation between secretoneurin and chromogranin A in patients with endocrine therapy failure (r = 0.543, p<0.05). There was no correlation between serum secretoneurin and prostate specific antigen, prostate acid phosphatase or interleukin-6. Gel filtration chromatography analysis of sera of 3 patients with D3 prostate cancer revealed a peak of secretoneurin immunoreactivity where intact secretoneurin elutes, thus showing that the processed peptide is circulating in the blood. Secretoneurin is elevated in sera of patients with endocrine therapy refractory prostate cancer. Our results support the concept that neuroendocrine differentiation is associated with prostate cancer progression.

Correlation between neovascularisation and neuroendocrine differentiation in prostatic carcinoma

Neuroendocrine (NE) differentiated tumor cells are found in almost all prostatic carcinomas. Prostatic carcinomas with a high NE differentiation have a poor prognosis and increased metastatic potential. A relationship between the neovascularisation density in the tumor and the metastatic potential in prostatic carcinoma is well known. NE cells and microvessels were demonstrated immunohistochemically on 102 radical prostatectomy specimens using antibodies against Chromogranin A and CD34. Standard areas (7.9 mm2) of maximal Chromogranin A expression and highest vascularisation were determined and topographically related by light microscopy. Area density of microvessels was evaluated morphometrically. NE tumor cells were present in all prostatic carcinomas studied. High grade prostatic carcinomas expressed significantly more NE tumor cells and exhibited a higher neovascularisation than low grade carcinomas. There was significantly higher neovascularisation in high grade tumors with many, as compared to high grade tumors with few, NE tumor cells. Poorer pathological staging correlated with increased neovascularisation and stronger NE differentiation. A topographical relationship between the area of maximal NE tumor cells and the area of highest neovascularisation was found in 80.4% of all cases. An analysis of variance revealed a large number of NE tumor cells as the only predictor of an increased neovascularisation (p = 0.0006). These observations support the concept that increased neovascularisation is influenced not only by poor pathological grading but also by a high NE differentiation.

Neuroendocrine differentiation in prostatic carcinoma.

Information is presented on prostatic neuroendocrine cells and neuroendocrine differentiation in prostatic carcinoma. The prognostic and therapeutic implications of neuroendocrine differentiation in prostatic carcinoma are reviewed. Data are presented that support the intriguing link between neuroendocrine differentiation, tumor progression, and androgen-independent prostate cancer. The hormones, and the receptors, expressed by prostatic neuroendocrine cells are investigated in order to elucidate their significance for prognosis and therapy. The prognostic significance of neuroendocrine differentiation in prostatic malignancy has been controversial, but recent studies employing markers such as chromogranin A and neuron-specific enolase suggest that neuroendocrine differentiation, as reflected by increased tissue expression and/or blood levels of these neuroendocrine secretory products, correlates with poor prognosis, tumor progression, and androgen-independence. Since all malignant neuroendocrine cells are devoid of androgen receptors and since neuroendocrine phenotypic expression is not suppressed by androgen ablation, clonal propagation of androgen receptor-negative neuroendocrine cells may play an important role in the pathway towards the androgen-independent state of prostatic carcinoma. This would have significant implications for the treatment of prostate cancer, as several of the hormones known to be expressed by neuroendocrine-differentiated, malignant prostatic cells are potential candidates for drug therapy. A limited number of hormones have been tested in this context, in particular somatostatin, bombesin, and serotonin. Neuroendocrine differentiation in carcinoma of the prostate appears to be associated with poor prognosis, tumor progression, and the androgen-independent state, for which there is currently no successful therapy. Therefore, new therapeutic protocols and trials need to be developed to test drugs based on neuroendocrine hormones and/or their antagonists. An evaluation of this new therapeutic approach against prostatic carcinoma with neuroendocrine differentiation, including hormone-refractory cancer, is easily justified, since these tumors are unresponsive to current modes of therapy.

Differentiation of prostatic carcinoma and benign prostatic hyperplasia: Correlation between dynamic Gd‐DTPA‐enhanced MR imaging and histopathology

One of the major factors limiting the staging accuracy of conventional magnetic resonance imaging (MRI) for prostatic carcinoma, is the similarity in signal intensity between tumor and coexisting benign prostatic hyperplasia (BPH). As neovascularity is an independent indicator of pathological state, dynamic contrast-enhanced MRI may yield additional information. This study correlates the histopathological findings from 12 radical prostatectomy patients on a region-by-region basis, with pharmacokinetic modeling of dynamic contrast-enhanced (0.2 mmol dimeglumine gadopentetate/kg), fast multiplanar spoilt gradient-recalled echo images, using a two-compartment simplex minimization technique. Quantitative analysis demonstrated differences in the amplitude of the initial contrast upslope and contrast exchange rate between tumor and fibromuscular BPH (P < 0.03 and P < 0.03, respectively) and for the contrast exchange rate between tumor and fibroglandular BPH (P < 0.04), providing improved delineation of intraprostatic tumor extent compared with conventional imaging techniques. J. Magn. reson. Imaging 1999; 9:311–316. © 1999 Wiley-Liss, Inc.

Differentiation of prostatic carcinoma and benign prostatic hyperplasia: correlation between dynamic Gd-DTPA-enhanced MR imaging and histopathology.

One of the major factors limiting the staging accuracy of conventional magnetic resonance imaging (MRI) for prostatic carcinoma, is the similarity in signal intensity between tumor and coexisting benign prostatic hyperplasia (BPH). As neovascularity is an independent indicator of pathological state, dynamic contrast-enhanced MRI may yield additional information. This study correlates the histopathological findings from 12 radical prostatectomy patients on a region-by-region basis, with pharmacokinetic modeling of dynamic contrast-enhanced (0.2 mmol dimeglumine gadopentetate/kg), fast multiplanar spoilt gradient-recalled echo images, using a two-compartment simplex minimization technique. Quantitative analysis demonstrated differences in the amplitude of the initial contrast upslope and contrast exchange rate between tumor and fibromuscular BPH (P<0.03 and P<0.03, respectively) and for the contrast exchange rate between tumor and fibroglandular BPH (P<0.04), providing improved delineation of intraprostatic tumor extent compared with conventional imaging techniques.

Neuroendocrine cells of the prostate and neuroendocrine differentiation in prostatic carcinoma: a review of morphologic aspects

Neuroendocrine cells of the prostate are intraepithelial regulatory cells that secrete serotonin and a variety of peptide hormones. It is hypothesized that these cells regulate both growth and differentiation, as well as exocrine secretory activity through endocrine, paracrine, neurocrine, and lumenocrine mechanisms. Neuroendocrine differentiation in prostatic carcinoma occurs as pure neuroendocrine malignancies, such as small-cell carcinoma and carcinoid/carcinoid-like tumors, as well as focal neuroendocrine differentiation in a more conventional prostatic adenocarcinoma. Neuroendocrine differentiation in prostatic carcinoma may have diagnostic and prognostic significance.

Neuroendocrine Differentiation in Prostatic Carcinoma During Hormonal Treatment

Objectives. Neuroendocrine differentiation (NED) is a common feature in adenocarcinoma of the prostate. Several studies suggest that NED may have a major impact on cancer progression as neuroendocrine (NE) secretory products have been shown to possess growth stimulatory effects. NED has also been proposed to constitute part of the mechanism by which a prostate cancer cell progresses toward androgen independence as NE tumor cells have been demonstrated to be devoid of androgen receptor immunoreactivity. In this retrospective study, we evaluated NED status in prostate cancer specimens from patients undergoing androgen ablation therapy. Methods. The degree of NED in transurethral resection of the prostate (TURP) samples from 53 patients with prostate cancer was investigated by immunocytochemistry using polyclonal rabbit immunoglobin G (IgG) against chromogranin A (CgA). Changes in NED with time were determined by a manual semiquantitative cell counting method. Results. During androgen withdrawal therapy, 21 tumors (40%) displayed increased NED concomitant with histopathologic tumor progression, whereas 29 carcinomas (55%) showed no change in NED status. However, a majority of the histopathologically unchanged tumors displayed marked NED at the first TURP and an increase in NED was by definition not possible. In only 3 cases (5%) was a decrease in NED observed with time. Conclusions. Androgen ablation therapy may be a contributing factor to the increase in NED of prostatic adenocarcinoma with time, and our findings imply that androgen withdrawal therapy enhances the selection and progression of NED, androgen-independent tumor cells.

Neuroendocrine differentiation in prostatic carcinoma: An update

Neuroendocrine differentiation in prostatic carcinoma may be related to the growth and prognosis of prostate cancer, especially androgen-insensitive tumors. This update reviews new investigations relating to neuroendocrine differentiation of prostatic carcinoma building on two previous review articles. All relevant publications are systematically reviewed. New developments include the detection of bombesin, calcitonin and serotonin receptors, as well as a clearer delineation of the role that neuroendocrine products play in the growth, invasiveness, and motility of prostate cancer. Prognostic studies are still somewhat contradictory, but those studies and studies related to serum/plasma levels of neuroendocrine products in prostate cancer suggest that neuroendocrine differentiation may be more important in androgen-independent tumors and metastatic tumors than in hormone-sensitive and locally recurrent tumors. New cell line xenograft and transgenic mouse models for neuroendocrine prostatic carcinoma are described and will provide the basis for further investigations into the role played by neuroendocrine differentiation in prostatic carcinoma. Neuroendocrine differentiation in prostatic carcinoma is of great potential significance but needs to be better defined before its significance can be accurately assessed.

Proton MRT2 Maps Correlate With The Citrate Concentration in the Prostate

A significant correlation between water T2 relaxation time and citrate concentration in the normal prostate is demonstrated using spatially localized spectroscopy and water T2 maps. These data imply that MR images may be used to infer the concentration of citrate at high spatial resolution. Preliminary results in patients demonstrate that this relationship is maintained in benign prostatic hyperplasia (BPH) and prostatic carcinoma. The determination of citrate concentration and water T2 may aid the differentiation of prostate carcinoma from BPH and normal tissue.

Neuroendocrine differentiation in the precursors of prostate cancer.

To review neuroendocrine differentiation in the precursors of prostatic carcinoma (prostatic intraepithelial neoplasia). Background information is given on the prostatic neuroendocrine cell and neuroendocrine differentiation in prostatic carcinoma. Neuroendocrine differentiation in prostatic intraepithelial neoplasia is reviewed. Neuroendocrine differentiation occurs in prostatic intraepithelial neoplasia and is intermediate in degree between normal (which has the most cells with neuroendocrine differentiation) and carcinoma. Neuroendocrine differentiation in the precursors of prostatic carcinoma may play a role in the pathogenesis of cancer but is speculative at this time. Methods to better assess neuroendocrine differentiation are needed.

Neuroendocrine differentiation in prostatic carcinoma. Recent findings and new concepts

Neuroendocrine cells of the prostate are intraepithelial regulatory cells that probably modulate both growth and differentiation as well as the exocrine secretory process. These cells form a component of the more generalized multiorgan regulatory system known as the amine precursor uptake and decarboxylation (APUD), or dispersed neuroendocrine system. The prostatic neuroendocrine cells contain serotonin and a variety of regulatory neuroendocrine peptides. Neuroendocrine differentiation in prostatic carcinoma is manifested as the relatively rare small cell carcinoma and the much more common, if not ubiquitous, focal neuroendocrine differentiation in conventional prostatic carcinoma. Neuroendocrine differentiation may have diagnostic, prognostic, and therapeutic implications. Recent findings include the expression of parathyroid hormone-related protein, the chromogranin peptide family, epidermal growth factor receptor, and c-erbB-2 immunoreactivity by prostatic neuroendocrine cells. Immunoreactive androgen receptor is not expressed by benign or malignant prostatic neuroendocrine cells. Non-neuroendocrine proliferation foci and bcl-2 immunoreactive cells appear to cluster around neuroendocrine cells in prostatic carcinoma. These findings, along with additional clinical and experimental evidence, suggest that neuroendocrine cells may play a role as an independent prognostic factor in prostate cancer, particularly those that are resistant to hormonal therapy. The therapeutic implications of prostatic neuroendocrine differentiation are discussed as are potential lines of investigation. Cancer 1995 ;75 :1850-9.