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-naïve 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-naïve 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.