TY - JOUR
T1 - PD-1, PD-L1, and CD163 in pancreatic undifferentiated carcinoma with osteoclast-like giant cells
T2 - expression patterns and clinical implications
AU - Luchini, Claudio
AU - Cros, Jerome
AU - Pea, Antonio
AU - Pilati, Camilla
AU - Veronese, Nicola
AU - Rusev, Borislav
AU - Capelli, Paola
AU - Mafficini, Andrea
AU - Nottegar, Alessia
AU - Brosens, Lodewijk A.A.
AU - Noë, Michaël
AU - Offerhaus, G. Johan A.
AU - Chianchiano, Peter
AU - Riva, Giulio
AU - Piccoli, Paola
AU - Parolini, Claudia
AU - Malleo, Giuseppe
AU - Lawlor, Rita T.
AU - Corbo, Vincenzo
AU - Sperandio, Nicola
AU - Barbareschi, Mattia
AU - Fassan, Matteo
AU - Cheng, Liang
AU - Wood, Laura D.
AU - Scarpa, Aldo
N1 - Funding Information:
Funding/Support: The authors acknowledge the following sources of funding: Cassini Project 2017, Associazione Italiana Ricerca Cancro ( 12182 ), FP7 European Community Grant Cam-Pac ( 602783 ), Italian Ministry of Health ( FIMP-CUP_J33G13000210001 ), NIH/NCI P50 CA62924 , NIH/NIDDK K08 DK107781 , Sol Goldman Pancreatic Cancer Research Center, Buffone Family Gastrointestinal Cancer Research Fund, Kaya Tuncer Career Development Award in Gastrointestinal Cancer Prevention, AGA-Bernard Lee Schwartz Foundation Research Scholar Award in Pancreatic Cancer, Sidney Kimmel Foundation for Cancer Research Kimmel Scholar Award, AACR-Incyte Corporation Career Development Award for Pancreatic Cancer Research, Rolfe Pancreatic Cancer Foundation, Joseph C Monastra Foundation, The Gerald O Mann Charitable Foundation (Harriet and Allan Wulfstat, Trustees), Sigma Beta Sorority, Progetto Trebionet, and Fondazione Caritro.
Publisher Copyright:
© 2018 Elsevier Inc.
PY - 2018/11
Y1 - 2018/11
N2 - 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.
AB - 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.
KW - Osteoclast
KW - PDAC
KW - Pancreatic cancer
KW - Tumor-associated macrophages
KW - UCOGC
UR - http://www.scopus.com/inward/record.url?scp=85053819159&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85053819159&partnerID=8YFLogxK
U2 - 10.1016/j.humpath.2018.07.006
DO - 10.1016/j.humpath.2018.07.006
M3 - Article
C2 - 30031096
AN - SCOPUS:85053819159
SN - 0046-8177
VL - 81
SP - 157
EP - 165
JO - Human pathology
JF - Human pathology
ER -