Claudin 18.2 Immunohistochemistry Expression in Gastric Cancer: A Systematic Review

克洛丹 免疫组织化学 癌症 医学 病理 表达式(计算机科学) 癌症研究 肿瘤科 内科学 紧密连接 生物 计算机科学 程序设计语言 细胞生物学
作者
Joan Lop,Pablo Santiago Díaz,Mónica Larrubia Loring,M Patriarca,Belén Lloveras,Mar Iglesias
出处
期刊:Applied Immunohistochemistry & Molecular Morphology [Lippincott Williams & Wilkins]
卷期号:33 (2): 61-69
标识
DOI:10.1097/pai.0000000000001248
摘要

Claudin 18.2 is a transmembrane protein, part of the tight-junction complex, selectively expressed in gastric epithelium. It is showing promising results as a target in advanced gastric cancer in phase 3 clinical trials using a monoclonal antibody against claudin 18.2. A systematic review on expression of claudin 18.2 in gastric cancer was performed using the PubMed database. The following search expression was used: ("Stomach Neoplasms" [Mesh]) AND (("claudin-18[TIAB]") OR ("CLDN18[TIAB]")). A total of n=99 articles were retrieved. Of those, 17 preclinical studies about claudin 18.2 expression by immunohistochemistry were selected. The results of those studies showed great variability in the criteria used for defining the thresholds for positivity of the stain. The proportion of claudin 18.2 positive cases varied between 24% and 83%. In works using a positivity threshold set at >40% or >70% of cells with membranous/cytoplasmic staining at 2+/3+ intensity, the average rate of positive cases was 50% or 30%, respectively (similar with clones 43-14A and EPR19202). Positivity of claudin 18.2 was associated with advanced stage, diffuse phenotype and PD-L1 and EBV positivity in some of the studies. Variability in criteria used to define claudin 18.2 positivity, as well as methodological differences, could explain the variation in the proportion of positive cases described, as well as the inconsistency of the association with clinical, molecular, and survival variables. The upcoming anticlaudin 18.2 therapy in advanced gastric cancer should prompt pathology laboratories to adjust their staining protocols and evaluation criteria in their series of patients, to further establish the association of claudin expression with clinical and molecular variables.
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