Small cell carcinoma of the prostate: An immunohistochemical study
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).
- SourceAvailable from: Shaobo Zhang
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- "Yao et al. showed that 15 out of 18 (83%) PSCC cases had positive TTF1 staining (Yao et al., 2006). Wang et al. reported 23 out of 44 cases (52.3%) with positive TTF1 staining (Wang and Epstein, 2008). These findings indicate that TTF1 immunostaining is not reliable for distinguishing primary PSCC from metastatic small cell carcinoma originating elsewhere. "
ABSTRACT: Small cell carcinoma of the prostate (PSCC) is a rare and highly aggressive malignancy with a dismal prognosis. Most patients present with advanced disease, including metastases to bone, viscera, and the central nervous system. Histologically, PSCC is indistinguishable from its pulmonary counterpart. Although PSCC may occur in pure form, as in small cell lung carcinoma, it also occurs in conjunction with conventional glandular prostate carcinoma, and may evolve from conventional adenocarcinoma during the course of hormonal therapy. Immunohistochemical staining is extremely helpful in establishing the diagnosis, a prerequisite, as in small cell lung cancer, for optimal therapeutic strategy. Currently, combinations of surgical resection, chemotherapy, and radiation therapy represent the main treatment options. Improvement in survival may depend upon the identiﬁcation of new molecular markers to facilitate earlier diagnosis and the development of novel targeted therapies. This review will discuss general aspects of PSCC, focusing on ways in which our understanding of PSCC has been advanced by studies of the histopathologic, immunohistochemical and molecular alterations in this disease.Histology and histopathology 11/2014; · 2.24 Impact Factor
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- "To date, the origin of these tumors remains uncertain. They can share similarities with basal/progenitor cells (P63+, c-Kit+) (19). This has led to the speculation that they derive from transformation of multipotential prostatic progenitors. "
ABSTRACT: In normal prostate, neuroendocrine (NE) cells are rare and interspersed among the epithelium. These cells are believed to provide trophic signals to epithelial cell populations through the secretion of an abundance of neuropeptides that can diffuse to influence surrounding cells. In the setting of prostate cancer (PC), NE cells can also stimulate surrounding prostate adenocarcinoma cell growth, but in some cases adenocarcinoma cells themselves acquire NE characteristics. This epithelial plasticity is associated with decreased androgen receptor (AR) signaling and the accumulation of neuronal and stem cell characteristics. Transformation to an NE phenotype is one proposed mechanism of resistance to contemporary AR-targeted treatments, is associated with poor prognosis, and thought to represent up to 25% of lethal PCs. Importantly, the advent of high-throughput technologies has started to provide clues for understanding the complex molecular profiles of tumors exhibiting NE differentiation. Here, we discuss these recent advances, the multifaceted manner by which an NE-like state may arise during the different stages of disease progression, and the potential benefit of this knowledge for the management of patients with advanced PC.Frontiers in Oncology 03/2014; 4:60. DOI:10.3389/fonc.2014.00060
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- "SCNC also tends to have frequent mitotic figures and areas of necrosis, which are rarely seen with adenocarcinoma. Immunohistochemically, adenocarcinoma is characterized by the expression of luminal differentiation markers such as CK8, CK18, AR and PSA (Figure 2), while SCNC shows focal, perinuclear staining pattern for cytokeratin, negative staining for AR and PSA and positive staining for NE markers chromogranin A (Figure 2), synaptophysin and CD56.101516 SCNC is also positive for P5317 and CD44,18 and occasionally TTF-1.10151619 "
ABSTRACT: Most prostate cancers (PCas) are classified as acinar type (conventional) adenocarcinoma which are composed of tumor cells with luminal differentiation including the expression of androgen receptor (AR) and prostate-specific antigen (PSA). There are also scattered neuroendocrine (NE) cells in every case of adenocarcinoma. The NE cells are quiesecent, do not express AR or PSA, and their function remains unclear. We have demonstrated that IL8-CXCR2-P53 pathway provides a growth-inhibitory signal and keeps the NE cells in benign prostate and adenocarcinoma quiescent. Interestingly, some patients with a history of adenocarcinoma recur with small cell neuroendocrine carcinoma (SCNC) after hormonal therapy, and such tumors are composed of pure NE cells that are highly proliferative and aggressive, due to P53 mutation and inactivation of the IL8-CXCR2-P53 pathway. The incidence of SCNC will likely increase due to the widespread use of novel drugs that further inhibit AR function or intratumoral androgen synthesis. A phase II trial has demonstrated that platinum-based chemotherapy may be useful for such therapy-induced tumors.Asian Journal of Andrology 02/2014; 16(4). DOI:10.4103/1008-682X.123669 · 2.53 Impact Factor