Small cell carcinoma of the prostate: an immunohistochemical study.

Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, and Department of Pathology, Rochester General Hospital, Rochester, NY 14642, USA.
American Journal of Surgical Pathology (Impact Factor: 4.59). 06/2006; 30(6):705-12. DOI: 10.1097/00000478-200606000-00005
Source: PubMed

ABSTRACT Small cell carcinoma of the prostate (SCPC) is morphologically similar to small cell carcinoma of the lung (SCLC) and maybe misinterpreted as Gleason pattern 5b prostate adenocarcinoma (HGPC). Recognition of SCPC is important because of its different clinical behavior. This study aims to characterize the immunophenotype of histologically classic SCPC using a comprehensive panel of markers, to better understand its histogenesis, aid in its classification, and evaluate potential therapeutic targets. Using the World Health Organization morphologic criteria for SCLC, 18 SCPC cases were identified; and studied for the following tumor marker groups: prostate specific/related, neuroendocrine, sex steroid hormone receptors, and prognostic/treatment target-related. Ten cases of UPC were used as controls. PSA was positive in 17% of SCPC and neuroendocrine markers were expressed in HGPC. PSA, TTF-1 and CD56 were the most helpful markers in differentiating between SCPC and HGPC (P<0.01), whereas bombesin/GRP, c-kit, bcl-2, and EGFR expression was more frequent in SCPC. SCPC is best diagnosed by following the World Health Organization diagnostic criteria for SCLC. Immunohistochemical markers can help separate SCPC from HGPC and may be useful in histologically borderline cases. Potential therapeutic targets are identified immunohistochemically in SCPC (Bombesin/GRP, c-kit, bcl-2, and EGFR).

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    ABSTRACT: Small cell carcinoma (SmCC) is a distinct clinicopathological entity first described in the lung. It represents approximately 15% of all bronchogenic carcinoma. Extrapulmonary small cell carcinoma (EPSmCC) morphologically indistinguishable from small cell lung cancer (SCLC) was first reported in 1930. Since its first description, EPSmCC has been reported in virtually all anatomical sites, including: gynecologic organs (ovary and cervix); genitourinary organs (urinary bladder and prostate); the gastrointestinal tract (esophagus); skin (Merkel cell carcinoma) and head and neck region. Regardless of the anatomic sites, all SmCCs have similar, if not identical, histo-pathology features and immunohistochemical profile. SmCC is one of the most aggressive malignancies. The molecular mechanisms underlying its development and progression remain poorly understood. Herein, we reviewed the literature in SmCC in respect to its site of occurrence, clinical features, immunohistochemical characteristics. SmCCs have heterogeneous molecular mutations. Dinstinct genetic alterations associated with SmCC from different body sites were reviewed. Some genetic alterations such as RB1, TP53 are commonly seen in different origins of SmCC. Other genes with site specificity were also summarized, such as bladder SmCC with TERT promoter mutations; prostate SmCC with ERG translocations; ovarian SmCC with SMARCA4 mutations; Merkel cell carcinoma (skin) and cervical SmCC with Merkel cell polyomavirus (MCV or MCPyV) and human papillomavirus (HPV). Further studies are needed to employ a genetically oriented approach for the diagnosis and therapy of SmCC.
    01/2015; 4:2. DOI:10.1186/2162-3619-4-2
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    ABSTRACT: Background The aim of this study was to analyze the frequency of Thyroid Transcription Factor (TTF)-1 expression in small cell lung cancer (SCLC) and its value for the diagnosis of SCLC, the response to first line treatment as well as the prognostic impact on overall survival (OS). Methods We analyzed a total of 294 patients (m, n = 184; f, n = 110) with SCLC (stage IIIA, n = 32; IIIB, n = 87; IV, n = 175) diagnosed in our institution between January 2005 and December 2008. Patient’s characteristics comprising age, gender, histology and first line treatment were included into the analyses. For the follow-up of patients the governmental death registrar was used. The TTF-1 immunostaining was prospectively performed. CT scans of all patients were reviewed and response to treatment was evaluated using the Response Evaluation Criteria In Solid Tumors 1.0 (RECIST) criteria. Results A total of 221 of the 294 patients were eligible for analysis. Patients with TTF-1-positive SCLC had a median OS of 374 (95% CI 306–442) days. The OS of patients with TTF1-negative SCLC was 290 (95% CI 191–389) days, which was not significantly shorter (p = 0.254). Also stratification for tumor stage did not reveal significant difference in OS. Analyzing the disease control rate (DCR) in patients with metastatic disease (stage IV), we observed a significantly (p = 0.006) improved response to treatment in the group of patients with TTF-1-expression (DCR 86% vs. 56%). Regarding the overall response rates (ORR) in the entire population, there was no difference observed between both subgroups. (TTF-1-pos. 75.3% vs. TTF-1-neg. 71.4%; p = 0.642). Conclusions The diagnostic information of TTF-1 in SCLC seems to be limited. TTF-1 had no prognostic value concerning OS, but may serve as a predictor for response to first line chemotherapy. Virtual slides The virtual slide(s) for this article can be found here:
    Diagnostic Pathology 04/2015; 10(1). DOI:10.1186/s13000-015-0250-z · 2.41 Impact Factor
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    ABSTRACT: Neuroendocrine differentiation (NED) marks a structural and functional feature of certain cancers, including prostate cancer (PCa), whereby the malignant tissue contains a significant proportion of cells displaying neuronal, endocrine, or mixed features. NED cells produce, and can secrete, a cocktail of mediators commonly encountered in the nervous system, which may stimulate and coordinate cancer growth. In PCa, NED appears during advanced stages, subsequent to treatment, and accompanies treatment resistance and poor prognosis. However, the term " neuroendocrine " in this context is intrinsically vague. This article seeks to provide a framework on which a unified view of NED might emerge. First, we review the mutually beneficial interplay between PCa and neural structures, mainly supported by cell biology experiments and neurological conditions. Next, we address the correlations between PCa and neural functions, as described in the literature. Based upon the integration of clinical and basic observations, we suggest that it is legitimate to seek for true neural differentiation, or neuromimicry, in cancer progression, most notably in PCa cells exhibiting what is commonly described as NED.
    Frontiers in Oncology 03/2015; 5(37). DOI:10.3389/fonc.2015.00037