Clinicopathologic Relevance of Claudin 18.2 Expression in Gastric Cancer: A Meta-Analysis

Abstract

An increasing number of tumor markers have been discovered to have potential efficacy as diagnostic and prognostic tools in gastric cancer. We aimed to assess putative correlations between claudin 18.2 expression and pathological or prognosis features in patients with gastric cancer. MEDLINE, Web of Science, EBSCO, and ClinicalTrials.gov were used to search for relevant studies from their inception to 30 October 2020. Finally, a total of six articles were included in this meta-analysis. Review Manager 5 software was applied to examine the heterogeneity among the studies and to calculate the odds ratio with 95% CI by selecting corresponding models, in evaluating the strength of the relationship. Publication bias test was also conducted. No bias and no significant correlations were found between CLDN 18.2 and TNM stages, Lauren classification, HER2, grading, or overall survival. This meta-analysis expounded that the relationship with CLDN 18.2 and pathological features depends on the percentage of staining of tumor cells for which CLDN 18.2 is considered positive. Our pooled outcomes suggest that targeted therapy for CLDN 18.2 could be effective if certain criteria were established.

Claudin-18 Immunohistochemical Staining Facilitates the Identification of Metastatic Carcinoma of Gastric or Pancreatic Origin in Effusion Specimens

“…15,17,18 However, a meta-analysis did not find any correlation between claudin-18.2 staining and clinicopathologic features. 4 Our data suggested that claudin-18 staining alone may lead to few gastric adenocarcinomas being undetected. A combination of this technique with a review of clinical history as well as staining for other IHC markers may reduce the possibility of misdiagnosis.…”

“…A wide range of expression rates of claudin-18 in gastric cancer, from 12.5% to 77%, were reported in other studies. 4,[16][17][18][19] Similarly, the reported positive rates in esophageal adenocarcinoma varied from 18.4% to 78%. 18,20 The wide ranges may reflect different sensitivity of antibody clones and scoring systems.…”

“…3 By immunohistochemistry, claudin-18 was frequently expressed in gastric cancer, but the reported frequency ranged from 12.5% to 86.6% in different studies. 4 Frequent ectopic expression of claudin-18 has also been reported in pancreatic adenocarcinoma and intraductal papillary mucinous neoplasm of the pancreas. 5,6 Because of the lack of expression in normal pancreatic tissue and frequent expression (89%) in pancreatic ductal adenocarcinoma, claudin-18 can be used as an immunocytochemical marker in biliary brushing cytology to increase the accuracy of diagnosing pancreatobiliary malignancies.…”

Gastric Cancer: Mechanisms, Biomarkers, and Therapeutic Approaches

“…CLDN18.2 expression was significantly associated with a diffuse histologic type, non-antral location, and EBV-positivity [41][42][43]. A majority of the studies reported that high expression of CLDN 18.2 was not associated with patient survival [42,[121][122][123][124].…”

“…In previous studies, CLDN18.2 expression in tumor cells was only determined by IHC [124]. Membranous staining of moderate to strong (2+/3+) intensity was regarded as high expression in tumor cells, and the proportion of CLDN18.2+ cells was calculated.…”