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Hum Pathol. 2018 Nov;81:157-165. doi: 10.1016/j.humpath.2018.07.006. Epub 2018 Jul 18.

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

Author information

1
Department of Diagnostics and Public Health, Section of Pathology, University of Verona, 37134 Verona, Italy.
2
Department of Pathology, Beaujon Hospital, 92110 Clichy, France; Paris-Diderot School of Medicine, Inflammation Research Center, 75013 Paris, France.
3
Department of Surgery, University and Hospital Trust of Verona, 37134 Verona, Italy.
4
Personalized Medicine, Pharmacogenomics, Therapeutic Optimization, Paris-Descartes University, 75006 Paris, France.
5
National Institute of Gastroenterology-Research Hospital, IRCCS "S. de Bellis," 70013, Castellana Grotte, Bari, Italy.
6
ARC-Net Research Center, University of Verona, 37134 Verona, Italy.
7
Department of Surgery, Section of Pathology, San Bortolo Hospital, 36100 Vicenza, Italy.
8
Department of Pathology, University Medical Center Utrecht, 3508 Utrecht, The Netherlands; Department of Pathology, Radboud University Medical Center, 6500, HB, Nijmegen, The Netherlands.
9
Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD 21211, USA.
10
Department of Pathology, University Medical Center Utrecht, 3508 Utrecht, The Netherlands.
11
Surgical Pathology Unit, Santa Chiara Hospital, 38122 Trento, Italy.
12
Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
13
Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD 21211, USA; Department of Oncology, Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD 21211, USA. Electronic address: ldwood@jhmi.edu.
14
Department of Diagnostics and Public Health, Section of Pathology, University of Verona, 37134 Verona, Italy; ARC-Net Research Center, University of Verona, 37134 Verona, Italy. Electronic address: aldo.scarpa@univr.it.

Abstract

Undifferentiated carcinoma with osteoclast-like giant cells (UCOGC), a variant of pancreatic ductal adenocarcinoma (PDAC), has a 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 extrapancreatic tumors with osteoclast-like giant cells and 10 pancreatic anaplastic carcinomas were immunostained using antibodies against PD-1, PD-L1, and CD163. In pancreatic UCOGCs, PD-L1 was expressed in neoplastic cells of 17 (63%) of 27 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 did patients with PD-L1-negative UCOGCs (hazard ratio, 3.397; 95% confidence interval, 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. Extrapancreatic tumors with osteoclast-like giant cells showed very similar staining patterns for the same proteins. Anaplastic carcinomas 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.

KEYWORDS:

Osteoclast; PDAC; Pancreatic cancer; Tumor-associated macrophages; UCOGC

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