TY - JOUR
T1 - PD-L1 in small bowel adenocarcinoma is associated with etiology and tumor-infiltrating lymphocytes, in addition to microsatellite instability
AU - Giuffrida, P.
AU - Arpa, G.
AU - Grillo, F.
AU - Klersy, C.
AU - Sampietro, G.
AU - Ardizzone, S.
AU - Fociani, P.
AU - Fiocca, R.
AU - Latella, G.
AU - Sessa, F.
AU - D’Errico, A.
AU - Malvi, D.
AU - Mescoli, C.
AU - Rugge, M.
AU - Nesi, G.
AU - Ferrero, S.
AU - Furlan, D.
AU - Poggioli, G.
AU - Rizzello, F.
AU - Macciomei, M.C.
AU - Santini, D.
AU - Volta, U.
AU - De Giorgio, R.
AU - Caio, G.
AU - Calabrò, A.
AU - Ciacci, C.
AU - D’Armiento, M.
AU - Rizzo, A.
AU - Solina, G.
AU - Martino, M.
AU - Tonelli, F.
AU - Villanacci, V.
AU - Cannizzaro, R.
AU - Canzonieri, V.
AU - Florena, A.M.
AU - Biancone, L.
AU - Monteleone, G.
AU - Caronna, R.
AU - Ciardi, A.
AU - Elli, L.
AU - Caprioli, F.
AU - Vecchi, M.
AU - D’Incà, R.
AU - Zingone, F.
AU - D’Odorico, A.
AU - Lenti, M.V.
AU - Oreggia, B.
AU - Reggiani Bonetti, L.
AU - Astegiano, M.
AU - Biletta, E.
AU - Cantoro, L.
AU - Giannone, A.G.
AU - Orlandi, A.
AU - Papi, C.
AU - Perfetti, V.
AU - Quaquarini, E.
AU - Sandri, G.
AU - Silano, M.
AU - Usai, P.
AU - Barresi, V.
AU - Ciccocioppo, R.
AU - Luinetti, O.
AU - Pedrazzoli, P.
AU - Pietrabissa, A.
AU - Viglio, A.
AU - Paulli, M.
AU - Corazza, G.R.
AU - Solcia, E.
AU - Vanoli, A.
AU - Di Sabatino, A.
N1 - Cited By :6
Export Date: 30 January 2021
PY - 2020
Y1 - 2020
N2 - 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.
AB - 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.
U2 - 10.1038/s41379-020-0497-0
DO - 10.1038/s41379-020-0497-0
M3 - Article
VL - 33
SP - 1398
EP - 1409
JO - Modern Pathology
JF - Modern Pathology
SN - 0893-3952
IS - 7
ER -