Examining CLDN18.2 as a Biomarker for Gastric, GEJ Cancers

Claudin 18 isoform 2 is an emerging therapeutic target in gastric and gastroesophageal (G/GEJ) cancers. As the dominant isoform of CLDN18 that is expressed in gastric cancers, it can also serve as a promising biomarker.

A new study by Rebecca Waters, DO, and colleagues sought to gain a better understanding of CLDN18.2 positivity patterns, prognostic implications, and associations with various characteristics in G/GEJ adenocarcinoma.

A total of 304 patients with G/GEJ adenocarcinoma had their archived tumor tissue samples studied for CLDN18.2 positivity using immunohistochemistry. Positivity was defined as ≥50% or ≥75% of tumor cells with CLDN18 staining intensity ≥2+.

CLDN18.2 positivity patterns were analyzed for association with prognosis and clinicopathologic/demographic characteristics. Where possible, positivity was analyzed for matched tissue samples to determine consistency between primary and metastatic tumors and concordance before and after chemotherapy.

CLDN18.2-positive tumors with ≥75% cutoff were found in 135 (44.4%) patients. The tumors had a prevalence of 51.4% (n=91 of 177) in gastric and 34.6% (n=44 of 127) in GEJ adenocarcinoma. With a ≥50% cutoff, the prevalence of CLDN18.2-positive tumors was 64.4% (n=114 of 177) in gastric adenocarcinoma and 44.9% (n=57 of 127) in GEJ adenocarcinoma.

No association was noted between overall survival and CLDN18.2 positivity using either threshold. Significant associations were seen between CLDN18.2 positivity and sex, histologic type of G/GEJ adenocarcinoma, adenocarcinoma subtype (≥75% cutoff), and metastasis site and tumor grade (≥50% cutoff).

The overall concordance of CLDN18.2 positivity with ≥75% cutoff was 73% (27 of 37) for matched primary against metastatic tumor samples and 74% (29 of 39) for matched samples before and after chemotherapy.

CLDN18.2 positivity was not found to be related to survival in G/GEJ adenocarcinoma, but appears to demonstrate >70% concordance as a biomarker. Further studies are warranted to determine the observed correlations between certain patient/tumor characteristics.