Programmed death ligand 1 (PD-L1) status and tumor-infiltrating lymphocytes in hot spots of primary and liver metastases in prostate cancer with neuroendocrine differentiation
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 biom...
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| Main Authors: | , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
2019
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| In: |
Clinical genitourinary cancer
Year: 2018, Volume: 17, Issue: 2, Pages: 145-153.e5 |
| ISSN: | 1938-0682 |
| DOI: | 10.1016/j.clgc.2018.12.007 |
| Online Access: | Verlag, Volltext: https://doi.org/10.1016/j.clgc.2018.12.007 Verlag, Volltext: http://www.sciencedirect.com/science/article/pii/S1558767318305895 
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| Author Notes: | Jost von Hardenberg, Sarah Hartmann, Katja Nitschke, Thomas Stefan Worst, Saskia Ting, Henning Reis, Philipp Nuhn, Cleo-Aron Weis, Philipp Erben |
| Summary: | 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. |
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| Item Description: | Available online 21 December 2018 Gesehen am 22.05.2019 |
| Physical Description: | Online Resource |
| ISSN: | 1938-0682 |
| DOI: | 10.1016/j.clgc.2018.12.007 |