Department of Pathology, Moffitt Cancer Center, Tampa, FL, U.S.A.
Pathology Laboratory, Florida Digestive Health Specialists, Bradenton, FL, U.S.A.
Cancer Genomics Proteomics. 2022 Mar-Apr;19(2):145-150. doi: 10.21873/cgp.20310.
BACKGROUND/AIM: 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.
背景/目的：具有微卫星不稳定高（MSI-H）或错配修复缺陷（dMMR）状态的癌症对免疫检查点抑制（ICI）有反应。无论肿瘤类型如何，MSI-H/dMMR 状态都是ICI 反应性的可靠生物标志物。本研究旨在确定食管腺癌（EAC）前体病变（如 Barrett 食管（BE）和伴有低级别异型增生（LGD）或高级别异型增生（HGD）的 BE）中的 MSI-H 状态。
我们进行了 PMS2、MSH6、PD1 和 PD-L1 的免疫组织化学染色（IHC）。
所有 BE（50 例）、LGD（48 例）和 HGD（50 例）病例均具有完整的 PMS2 和 MSH6 核表达；PD1 阴性；PD-L1 联合阳性评分（CPS）<1。1 例 EAC 病例（2%）PMS2 核表达阴性。1 例 HGD 病例（2%）和 2 例 EAC 病例（4%）PD1 阳性（PD1 的 CPS 评分<1 适用）。1 例 EAC 病例（2%）CPS 评分>1，1 例 EAC 病例（2%）MSI-H。MSI-H 肿瘤通常表现出 PD-L1 表达，尽管本研究中的 MSI-H EAC 的 PD-L1 CPS 评分<1。
进一步研究 EAC 及其前体病变的 PD1、PD-L1 和 dMMR 状态可能有助于了解 EAC 进化的免疫原性。
