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.

PD-L1 in small bowel adenocarcinoma is associated with etiology and tumor-infiltrating lymphocytes, in addition to microsatellite instability / 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.; Macciomei, M. C.; Santini, D.; Volta, U.; De Giorgio, R.; Caio, G.; Calabro, A.; Ciacci, C.; D'Armiento, M.; Rizzo, A.; Solina, G.; Martino, M.; Tonelli, F.; Villanacci, V.; Cannizzaro, R.; Canzonieri, V.; Florena, A. M.; Biancone, L.; Monteleone, G.; Caronna, R.; Ciardi, A.; Elli, L.; Caprioli, F.; Vecchi, M.; D'Inca, R.; Zingone, F.; D'Odorico, A.; Lenti, M. V.; Oreggia, B.; Reggiani Bonetti, L.; Astegiano, M.; Biletta, E.; Cantoro, L.; Giannone, A. G.; Orlandi, A.; Papi, C.; Perfetti, V.; Quaquarini, E.; Sandri, G.; Silano, M.; Usai, P.; Barresi, V.; Ciccocioppo, R.; Luinetti, O.; Pedrazzoli, P.; Pietrabissa, A.; Viglio, A.; Paulli, M.; Corazza, G. R.; Solcia, E.; Vanoli, A.; Di Sabatino, A.. - In: MODERN PATHOLOGY. - ISSN 0893-3952. - 33:7(2020), pp. 1398-1409. [10.1038/s41379-020-0497-0]

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

D'Armiento M.;Caronna R.
Investigation
;
Ciardi A.;
2020

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.
2020
small bowel adenocarcinoma, tumor-infiltrating lymphocytes, microsatelliteinstability
01 Pubblicazione su rivista::01a Articolo in rivista
PD-L1 in small bowel adenocarcinoma is associated with etiology and tumor-infiltrating lymphocytes, in addition to microsatellite instability / 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.; Macciomei, M. C.; Santini, D.; Volta, U.; De Giorgio, R.; Caio, G.; Calabro, A.; Ciacci, C.; D'Armiento, M.; Rizzo, A.; Solina, G.; Martino, M.; Tonelli, F.; Villanacci, V.; Cannizzaro, R.; Canzonieri, V.; Florena, A. M.; Biancone, L.; Monteleone, G.; Caronna, R.; Ciardi, A.; Elli, L.; Caprioli, F.; Vecchi, M.; D'Inca, R.; Zingone, F.; D'Odorico, A.; Lenti, M. V.; Oreggia, B.; Reggiani Bonetti, L.; Astegiano, M.; Biletta, E.; Cantoro, L.; Giannone, A. G.; Orlandi, A.; Papi, C.; Perfetti, V.; Quaquarini, E.; Sandri, G.; Silano, M.; Usai, P.; Barresi, V.; Ciccocioppo, R.; Luinetti, O.; Pedrazzoli, P.; Pietrabissa, A.; Viglio, A.; Paulli, M.; Corazza, G. R.; Solcia, E.; Vanoli, A.; Di Sabatino, A.. - In: MODERN PATHOLOGY. - ISSN 0893-3952. - 33:7(2020), pp. 1398-1409. [10.1038/s41379-020-0497-0]
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