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.

Giuffrida, P., Arpa, G., Grillo, F., Klersy, C., Sampietro, G., Ardizzone, S., et al. (2020). Correction: PD-L1 in small bowel adenocarcinoma is associated with etiology and tumor-infiltrating lymphocytes, in addition to microsatellite instability. MODERN PATHOLOGY [10.1038/s41379-020-0512-5].

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

Biancone, Livia
Membro del Collaboration Group
;
Orlandi, Augusto
Membro del Collaboration Group
;
2020-03-04

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.
4-mar-2020
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore MED/12 - GASTROENTEROLOGIA
English
Giuffrida, P., Arpa, G., Grillo, F., Klersy, C., Sampietro, G., Ardizzone, S., et al. (2020). Correction: PD-L1 in small bowel adenocarcinoma is associated with etiology and tumor-infiltrating lymphocytes, in addition to microsatellite instability. MODERN PATHOLOGY [10.1038/s41379-020-0512-5].
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, Mc; Santini, D; Volta, U; De Giorgio, R; Caio, G; Calabrò, A; Ciacci, C; D'Armiento, M; Rizzo, A; Solina, G; Martino, M; Tonelli, F; Villanacci, V; Cannizzaro, R; Canzonieri, V; Florena, Am; Biancone, L; Monteleone, G; Caronna, R; Ciardi, A; Elli, L; Caprioli, F; Vecchi, M; D'Incà, R; Zingone, F; D'Odorico, A; Lenti, Mv; Oreggia, B; Bonetti, Lr; Astegiano, M; Biletta, E; Cantoro, L; Giannone, Ag; 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, Gr; Solcia, E; Vanoli, A; Di Sabatino, A
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/234694
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