LAUSR

Background: Prostate cancer with neuroendocrine differentiation (NEPCA) shares similarities in tumor biology with small‐cell lung cancer. While immunotherapies were successfully tested in small‐cell lung cancer, and programmed death ligand 1 (PD‐L1) expression arises as an essential predictive biomarker, the local immune status in NEPCA is still poorly described. Patients and Methods: Paraffin‐embedded tissue samples of 39 patients (7 adenocarcinomas with neuroendocrine differentiation [ACA NED], 20 small‐cell neuroendocrine carcinomas, 2 well‐differentiated neuroendocrine tumors of NEPCA, and 10 adenocarcinoma liver metastases) were examined retrospectively by immunohistochemistry of chromogranin A (CGA), CD56, synaptophysin (SYN), CD3, and PD‐L1. Laser capture microdissection was used for neuroendocrine hot‐spot evaluation for additional real‐time reverse transcription‐quantitative PCR analysis (PD‐L1, CGA, CD56, SYN, GRP, ASCL1, and DLK1). Results: PD‐L1 immunohistochemistry expression in NEPCA was observed by assay E1L3N in 5 (20.8%) of 24 samples, but not by assay 22c3. Gene expression of PD‐L1 could be evaluated in 18 (62%) of 29 samples. Nine (69%) of 13 prostate specimens and 2 (40%) of 5 liver metastases were positive for PD‐L1. In ACA NED 4 (80%) of 5 and in small‐cell neuroendocrine carcinomas 6 (50%) of 12 specimens were positive for PD‐L1. Tumor‐infiltrating lymphocytes ≥ 10% were observed in 9 (37.5%) of 24 specimens. Low ASCL1 expression was observed in liver metastases. Conclusion: These data identify molecular PD‐L1 features in NEPCA. The predictive role of PD‐L1 status and tumor‐infiltrating lymphocytes in NEPCA remains to be established. MICRO‐ABSTRACT Prostate cancer subtypes with neuroendocrine differentiation share aggressive clinical features with limited responses to chemotherapy. Programmed death ligand 1 (PD‐L1) expression, a potential predictive biomarker for immunotherapy, could pave the way for immunotherapy. A retrospective immunohistochemical analysis of tissue samples found that primary tumors and liver metastases show moderate to high PD‐L1 messenger RNA in hot spots, but only in a subset of samples at the protein level.