Neuroendocrine differentiation (NED) has been recognized in prostatic adenocarcinomas. NED prostate adenocarcinoma represent a subset of aggressive tumor phenotypes which may be associated with therapeutic resistance and dismal outcome. Genomic and transcriptomic studies have suggested that there is marked intra-tumor heterogeneity of neuroendocrine differentiation in prostatic adenocarcinoma. NED tumors surges with increase in tumor grade and/or stage prostate cancers particularly in hormone-treated and hormone-refractory tumors. However, the prognostic value of NED in prostate adenocarcinoma is not well understood due to conflicting results in reported studies. We hypothesize that the heterogeneous nature of NED in prostate cancer may contribute to the difficulty in predicting outcomes in morphologically similar tumor specimens. In this study, 36 radical prostatectomy cases with a diagnosis of prostatic adenocarcinoma were procured from the archive of the Department of Pathology at the University Hospitals Cleveland Medical Center, including 18 patients who developed recurrent cancer after curative surgery with PSA level >0.1 ng/mL, and 18 patients whose cancers did not recur during matched follow up times. NED was subjectively evaluated by performing immunohistochemistry (IHC) for Chromogranin A (CgA), a neuroendocrine differentiation marker, and the scores were evaluated independently by two pathologist. Ten areas were randomly selected from areas of cancer present on each whole mount section, and the CgA IHC staining intensity in these areas was graded from 0-5, wherein 0 represents no staining and 4 represents strong staining. CgA staining intensity was positively associated with rise in serum PSA level. A significant intratumoral heterogeneity of CgA staining intensity was observed. The cumulative CgA scores from 10 areas were higher in specimens from patients whose cancers relapsed, as compared with specimens from patients whose cancers did not recur. Average cumulative CgA score was noted to be 18.72 ± 2.78 in the relapsed group and 8.28 ± 1.44 in the remission group. Taken together, the study revealed that intra-tumor heterogeneity of NED exists in prostate adenocarcinoma and influences the precise evaluation of NED in clinical specimens. Though the data is not conclusive, we do observe a lower level of NED in patients with remission compared to patients with a clinical failure in treatment by thorough evaluation of NED in prostate whole mount sections. This study potentially provides guidance to clinical usage of NED markers in prostate adenocarcinoma.

Citation Format: Menglei Zhu, Wei Chen, Michael Glover, Eswar Shankar, Gregory T. MacLennan, Sanjay Gupta. Prognostic role of neuroendocrine differentiation marker in prostate adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr LB-255. doi:10.1158/1538-7445.AM2017-LB-255