PD-L1 in small bowel adenocarcinoma is associated with etiology and tumor-infiltrating lymphocytes, in addition to microsatellite instability

Paolo Giuffrida, Giovanni Arpa, Federica Grillo, Catherine Klersy, Gianluca Sampietro, Sandro Ardizzone, Paolo Fociani, Roberto Fiocca, Giovanni Latella, Fausto Sessa, Antonietta D’Errico, Deborah Malvi, Claudia Mescoli, Massimo Rugge, Gabriella Nesi, Stefano Ferrero, Daniela Furlan, Gilberto Poggioli, Fernando Rizzello, Maria C. MacciomeiDonatella Santini, Umberto Volta, Roberto De Giorgio, Giacomo Caio, Antonio Calabrò, Carolina Ciacci, Maria D’Armiento, Aroldo Rizzo, Gaspare Solina, Michele Martino, Renato Cannizzaro, Vincenzo Canzonieri, Luca Elli, Flavio Caprioli, Maurizio Vecchi, Marco Vincenzo Lenti, Barbara Oreggia, Vittorio Perfetti, Erica Quaquarini, Marco Silano, Rachele Ciccocioppo, Ombretta Luinetti, Paolo Pedrazzoli, Andrea Pietrabissa, Alessandra Viglio, Marco Paulli, Gino R. Corazza, Enrico Solcia, Alessandro Vanoli, Antonio Di Sabatino

Research output: Contribution to journalArticle

Abstract

Small bowel adenocarcinomas (SBAs) are often associated with poor prognosis and have limited therapeutic options. Programmed cell death protein-1 (PD-1)/programmed cell death ligand 1 (PD-L1) pathway blockade is an effective treatment in many microsatellite instability-high (MSI-H) solid tumors. We aimed at investigating PD-L1 and PD-1 expression in non-hereditary, non-ampullary SBAs, associated with celiac disease (CeD), Crohn’s disease (CrD), or sporadic, recruited through the Small Bowel Cancer Italian Consortium. We assessed PD-L1 and PD-1 by immunohistochemistry in a series of 121 surgically resected SBAs, including 34 CeD-SBAs, 49 CrD-SBAs, and 38 sporadic SBAs. PD-L1 and PD-1 expression was correlated with several clinico-pathological features, such as the etiology, microsatellite instability status, and tumor-infiltrating lymphocyte (TIL) density. The prevalence of PD-L1 positivity according to combined positive score (CPS) was 26% in the whole cohort of SBAs, with significantly (p = 0.001) higher percentage (35%) in both CeD-SBAs and CrD-SBAs in comparison with sporadic SBAs (5%). CPS ≥ 1 SBAs were significantly (p = 0.013) more frequent in MSI-H cases (41%) than in non-MSI-H ones (18%); however, 15 CPS ≥ 1 microsatellite stable SBAs were also identified. CPS ≥ 1 SBAs showed higher TIL and PD-1+ immune cell density, more frequently medullary histotype, as well as a better outcome in comparison with CPS < 1 cases. This study demonstrates an increased proportion of PD-L1+ cases in both CeD-SBAs and CrD-SBAs in comparison with sporadic SBAs. In addition, the identification of a subset of PD-L1+ microsatellite stable SBAs supports the need to ascertain additional biomarkers of response to immune checkpoint inhibitors along with MSI-H.

Original languageEnglish
JournalModern Pathology
DOIs
Publication statusAccepted/In press - Jan 1 2020

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ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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Giuffrida, P., Arpa, G., Grillo, F., Klersy, C., Sampietro, G., Ardizzone, S., Fociani, P., Fiocca, R., Latella, G., Sessa, F., D’Errico, A., Malvi, D., Mescoli, C., Rugge, M., Nesi, G., Ferrero, S., Furlan, D., Poggioli, G., Rizzello, F., ... Di Sabatino, A. (Accepted/In press). PD-L1 in small bowel adenocarcinoma is associated with etiology and tumor-infiltrating lymphocytes, in addition to microsatellite instability. Modern Pathology. https://doi.org/10.1038/s41379-020-0497-0