Comparative study of neuroendocrine acquisition and biomarker expression between neuroendocrine and usual prostatic carcinoma.

BACKGROUND Neuroendocrine prostatic carcinoma (NEPC) is uncommon. The pathogenesis, clinical association, and clinical implications of this disease are still evolving. METHODS Clinicopathologic, immunohistochemical and genomic studies were used to investigate the incidence of NEPC in various clinicopathologic settings and the expression of various biomarkers in NEPC and non-NEPC as well as small cell NEPC. The study included 45 treatment-naive Gleason pattern (GP) 3 and 94 GP 4/5, 43 post-radiation, 60 post-androgen deprivation therapy (ADT), 38 lymph node metastatic and 9 small cell prostatic adenocarcinomas (PCs). RESULTS NEPC was found in 7% GP3, 10% GP4/5, 9% post-radiation, 18% post-ADT, and 5% lymph node metastatic PCs, respectively. Compared with treatment-naive PCs, post-ADT PCs showed significantly increased incidence of NEPC (p < .05) while no significant difference was noted between low- and high-grade PCs, post-radiation, and lymph node metastatic PCs. Serotonin was uniformly positive in NE cells of benign glands but negative in NEPC. Significant increase of Bcl-2 and Auro A and decrease of prostein were noted in NEPC (p < .05). No significant changes in the expression of other biomarkers were found. In addition, small cell NEPC was strongly associated with ADT (44%) and high Gleason score (≥8, 100%) and often presented with alterations of TP53/RB1 and ARID1A/B or other genes crucial to genomic fidelity. CONCLUSION Given that no specific treatment for NEPC is presently available, the findings in this study have significant implications in the better understanding of this often-deadly disease both clinically and pathogenetically as well as future patient management, including targeted therapy.