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

Authors :
Claudio Luchini
Alessia Nottegar
Antonio Pea
Jérôme Cros
Claudia Parolini
Lodewijk A.A. Brosens
Mattia Barbareschi
Vincenzo Corbo
Rita T. Lawlor
Camilla Pilati
Paola Piccoli
Laura D. Wood
Matteo Fassan
Paola Capelli
Aldo Scarpa
Peter Chianchiano
Giulio Riva
Nicola Sperandio
G. Johan A. Offerhaus
Giuseppe Malleo
Nicola Veronese
Andrea Mafficini
Michaël Noë
Liang Cheng
Borislav Rusev
Luchini, C.
Cros, J.
Pea, A.
Pilati, C.
Veronese, N.
Rusev, B.
Capelli, P.
Mafficini, A.
Nottegar, A.
Brosens, L.A.A.
Noë, M.
Offerhaus, G.J.A.
Chianchiano, P.
Riva, G.
Piccoli, P.
Parolini, C.
Malleo, G.
Lawlor, R.T.
Corbo, V.
Sperandio, N.
Barbareschi, M.
Fassan, M.
Cheng, L.
Wood, L.D.
Scarpa, A.
Source :
Human Pathology, 81, pp. 157-165, Human Pathology, 81, 157-165, Human Pathology, 81, 157. W.B. Saunders Ltd
Publication Year :
2018

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. © 2018 Elsevier Inc.

Details

ISSN :
00468177
Database :
OpenAIRE
Journal :
Human Pathology, 81, pp. 157-165, Human Pathology, 81, 157-165, Human Pathology, 81, 157. W.B. Saunders Ltd
Accession number :
edsair.doi.dedup.....9ae7c9526a2455e0983b64601e591720