Claudin 18.2 Expression in Gastric Tumors and Other Tumor Types With Gastric Epithelium-like Differentiation

Claudin 18.2 is an emerging biomarker for claudin 18.2-targeted therapy. We investigated claudin 18.2 expression in diverse tumor types.

We retrospectively analyzed 67 gastric tumors (61 surgically resected and six biopsy specimens) and 73 other tumor types (69 resected and four biopsy specimens), including those from the pancreas, hepatobiliary system, lung, ovary, uterine cervix, and others. Claudin 18.2 expression and positivity (≥75% of tumor cells showing moderate to strong membranous staining) were assessed using claudin 18 immunostaining (clone 43-14A).

Claudin 18.2 positivity was found in 47.8% (32/67) of gastric tumor samples. Epstein-Barr virus-associated gastric cancer showed a higher frequency of positivity (6/7, 85.7%), although not statistically significantly (p=0.216). Among gastric tumors from patients with lymph node or distant metastasis (n=20), four (20.0%) exhibited discrepancies in claudin 18.2 positivity between the primary and its metastasis. In other tumor types, claudin 18.2 positivity was more frequent in those with gastric epithelium-like differentiation, including pancreatic tumors (2/9, 22.2%), hepatobiliary carcinoma (2/8, 25.0%), invasive mucinous lung adenocarcinoma (4/5, 80.0%), and mucinous ovarian tumor (5/5, 100.0%) than in those with other histology (p<0.001). Interestingly, pancreatic tumors, potential candidates for claudin 18.2-targeted therapy, often exhibited reduced or lack of claudin 18.2 expression in the invasive component.

Overall, claudin 18.2 positivity occurred primarily in a significant proportion of gastric tumors and other tumors with gastric epithelium-like differentiation. Evaluating claudin 18.2 expression in all such tumors can benefit patients by guiding targeted therapy. Additionally, claudin 18.2 immunostaining serves as a lineage marker for gastric origin or gastric-like differentiation.