Programmed death‐ligand 1 expression in gastric cancer: correlation with mismatch repair deficiency and HER 2‐negative status

Gastric cancer ( GC ) is one of the most common malignancies. Immunotherapy is a promising targeted treatment. The immune regulatory programmed death‐1 ( PD ‐1)/programmed death‐ligand 1 ( PD ‐L1) axis has been used as a checkpoint target for immunotherapy. Currently, considerable discrepancies exist concerning the expression status of PD ‐L1 and its prognostic value in GC . We aimed to evaluate the expression rates of PD ‐L1 in GC , and further assess its relationship with mismatch repair ( MMR ), and human epidermal growth factor receptor 2 ( HER 2) status. We retrospectively collected 550 consecutive cases of GC in Fudan University Shanghai Cancer Center from 2010 to 2012. PD ‐L1, MMR protein, and HER 2 status were detected by immunohistochemistry ( IHC ). Fluorescence in situ hybridization was further used in HER 2 IHC 2+ cases. Cases with at least 1% membranous and/or cytoplasmic PD ‐L1 staining in either tumor cells ( TC s) or tumor‐infiltrating immune cells ( TIIC s) were considered as PD ‐L1 positive. The correlation between clinicopathological parameters, HER 2, MMR , and PD ‐L1 expression status was determined using chi‐squared tests. About 37.3% cases (205/550) showed PD ‐L1 expression in TC s and/or TIIC s. 17.3% cases (95/550) showed PD ‐L1 expression in TC s, 34.5% (190/550) cases showed PD ‐L1 expression in TIIC s. There were 45 deficient MMR ( dMMR ) cases (8.2%), which showed higher rates of PD ‐L1 expression compared with MMR ‐proficient carcinomas (60.0% vs. 35.2%, P = 0.001). HER 2 was positive in 66 (12.0%) cases. The expression of PD ‐L1 occurred more frequently in HER 2‐negative group than HER 2‐positive cohorts (39.0% vs. 24.2%, P = 0.020). The survival analysis revealed that PD ‐L1 was not associated with prognosis. This study evaluated the association between the PD ‐L1 expression and a specific subgroup ( dMMR and HER 2‐negative) in a large Asian cohort of GC . GC patients with dMMR and HER 2‐negative status exhibited higher PD ‐L1 expression rates. Our finding indicated that MMR and HER ‐2 status might be potential biomarkers for anti‐ PD ‐L1 therapy.