Claudio Luchini1, Jerome Cros2,3, Antonio Pea4, Camilla Pilati5, Nicola Veronese6, Borislav Rusev7, Paola Capelli1, Andrea Mafficini7, Alessia Nottegar8, Lodewijk A. A. Brosens9,10, Michaël Noë11, G. Johan A. Offerhaus9, Peter Chianchiano11, Giulio Riva1, Paola Piccoli1, Claudia Parolini1, Giuseppe Malleo4, Rita T Lawlor7, Vincenzo Corbo7, Nicola Sperandio1, Mattia Barbareschi12, Matteo Fassan7, Liang Cheng13, Laura D. Wood11,14, Aldo Scarpa1,7
1Department of Diagnostics and Public Health, Section of Pathology, University of Verona, Verona, Italy;2Department of Pathology, Beaujon Hospital, Clichy, France;3Paris-Diderot School of Medicine, Inflammation Research Center, Paris, France;4Department of Surgery, University and Hospital Trust of Verona, Verona, Italy;5Personalized Medicine, Pharmacogenomics, Therapeutic Optimization, Paris-Descartes University, Paris, France;6National Institute of Gastroenterology-Research Hospital, IRCCS “S. de Bellis”, Castellana Grotte, Bari, Italy;7ARC-Net Research Center, University of Verona, Verona, Italy; 8Department of Surgery, San Bortolo Hospital, Vicenza, Italy;9Department of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands;10Department of Pathology, Radboud University Medical Center, PO Box 9101, 6500 HB, Nijmegen, The Netherlands;11Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA;12Surgical Pathology Unit, Santa Chiara Hospital, Trento, Italy;13Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, USA;14Department of Oncology, Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
Abstract: One of the variants of pancreatic ductal adenocarcinoma (PDAC), the undifferentiated carcinoma with osteoclast-like giant cells (UCOGCs), has been recently studied with whole-exome sequencing. Despite striking similarities of somatic mutations with PDAC, the clinical course of UCOGC is very different from PDAC. Considering the relevance of immunotherapy markers in solid tumors, we investigated the expression of PD-1, PD-L1 and CD163 in a series of UCOGC. To this aim, 23 pancreatic UCOGC (10 pure and 13 PDAC-associated) and 5 extra-pancreatic tumors with osteoclast-like giant cells were immunostained using antibodies against PD-1, PD-L1 and CD163. In pancreatic UCOGC, PD-L1 was expressed in neoplastic cells of 15/23 (65%) cases, more often in cases with an associated PDAC (11/13) (P=0.039). This marker showed a poor prognostic value, confirmed at multivariable analysis: patients with PD-L1 positive UCOGC had a risk of all-cause mortality of more than 3 times fold than those with PD-L1 negative tumors (HR: 3.340; 95% CI: 1.062–17.999; P=0.036). PD-1 was expressed on rare lymphocytes in 10 UCOGC (43.5%), mainly located at the tumor periphery. CD163 was expressed on histiocytes, with a diffuse and strong staining pattern in all UCOGCs. Extra-pancreatic cases showed very similar staining patterns for the same biomarkers. Concluding, we report the expression of PD-L1, PD-1 and CD163 in a significant number of UCOGC, and show that PD-L1 has prognostic significance. Our results may have important implications for the immunotherapeutic strategies in this tumor type, and possibly for tumors with osteoclast-like giant cells of other organs.
doi: 10.21037/apc.2018.AB021
