Expression of DNA Mismatch Repair Proteins, PD1 and PDL1 in Barrett's Neoplasia

Cancers with a microsatellite instability-high (MSI-H) or deficient mismatch repair (dMMR) status respond to immune checkpoint inhibition (ICI). Regardless of the tumor type, MSI-H/dMMR status is a reliable biomarker for ICI responsiveness. This study aimed at determining the MSI-H status in precursor lesions to esophageal adenocarcinoma (EAC) such as Barrett's esophagus (BE) and BE with either low-grade dysplasia (LGD) or high-grade dysplasia (HGD).

We performed immunohistochemical staining (IHC) for PMS2, MSH6, PD1, and PD-L1.

All cases of BE (50), LGD (48), and HGD (50) had intact PMS2 and MSH6 nuclear expression; were negative for PD1; and had a PD-L1 combined positive score (CPS) score <1. One EAC case (2%) was negative for PMS2 nuclear expression. One HGD case (2%) and two EAC cases (4%) were PD1 positive (CPS score <1 applied to PD1). One EAC case (2%) had a CPS score >1, and one EAC case (2%) was MSI-H. MSI-H tumors usually show PD-L1 expression, although the MSI-H EAC in this study had a PD-L1 CPS score of <1.

Further studies investigating EAC and its precursor lesions for PD1, PD-L1, and dMMR status may be informative regarding the immunogenicity of the evolution of EAC.