PD-1, PD-L1 and CD163 in pancreatic undifferentiated carcinoma with osteoclast-like giant cells: expression patterns and clinical implications

Luchini, ClaudioCros, JeromePea, AntonioPilati, CamillaVeronese, NicolaRusev, BorislavCapelli, PaolaMafficini, AndreaNottegar, AlessiaBrosens, Lodewijk A. A.Noë, MichaëlOfferhaus, G. Johan A.Chianchiano, PeterRiva, GiulioPiccoli, PaolaParolini, ClaudiaMalleo, GiuseppeLawlor, Rita T.Vincenzo, CorboSperandio, NicolaBarbareschi, MattiaFassan, MatteoCheng, LiangWood, Laura D.Scarpa, Aldo2018-09-142018-09-142018Luchini, C., Cros, J., Pea, A., Pilati, C., Veronese, N., Rusev, B., … Scarpa, A. (2018). PD-1, PD-L1 and CD163 in pancreatic undifferentiated carcinoma with osteoclast-like giant cells: expression patterns and clinical implications. Human Pathology. https://doi.org/10.1016/j.humpath.2018.07.006https://hdl.handle.net/1805/17308Undifferentiated carcinoma with osteoclast-like giant cells (UCOGC), a variant of pancreatic ductal adenocarcinoma (PDAC), has striking genetic similarity to PDAC but a significantly improved overall survival. We hypothesize that this difference could be due to the immune response to the tumor, and as such, we investigated the expression of PD-1, PD-L1 and CD163 in a series of UCOGC. To this aim, 27 pancreatic UCOGCs (11 pure and 16 PDAC-associated), 5 extra-pancreatic tumors with osteoclast-like giant cells and 10 pancreatic anaplastic carcinomas (ACs) were immunostained using antibodies against PD-1, PD-L1 and CD163. In pancreatic UCOGCs, PD-L1 was expressed in neoplastic cells of 17/27 (63%) cases, more often in cases with an associated PDAC (P = .04). Expression of PD-L1 was associated with poor prognosis, confirmed by multivariate analysis: patients with PD-L1-positive UCOGCs had a risk of all-cause mortality that was 3 times higher than patients with PD-L1-negative UCOGCs (HR: 3.397, 95%CI: 1.023–18.375, P = .034). PD-L1 expression on tumor cells was also associated with aberrant P53 expression (P = .035). PD-1 was expressed on rare lymphocytes in 12 UCOGCs (44.4%), mainly located at the tumor periphery. CD163 was expressed on histiocytes, with a diffuse and strong staining pattern in all UCOGCs. Extra-pancreatic tumors with osteoclast-like giant cells showed very similar staining patterns for the same proteins. ACs have some similarities to UCOGCs, but PD-L1 has no prognostic roles. Our results may have important implications for immunotherapeutic strategies in UCOGCs; these tumors may also represent a model for future therapeutic approaches against PDAC.enPublisher PolicyUCOGCPDACosteoclastPD-1, PD-L1 and CD163 in pancreatic undifferentiated carcinoma with osteoclast-like giant cells: expression patterns and clinical implicationsArticle