Clinicopathological and molecular features of claudin-18 isoform 2 expression in patients with colorectal cancer: a single-center retrospective study

Background: Claudin-18 isoform 2 (CLDN18.2) is expressed in multiple cancers and is a promising target for antitumor therapy. However, there is limited knowledge regarding the prevalence and characteristics of CLDN18.2-positive colorectal cancer (CRC). Objectives: To determine the clinicopathological and molecular features of patients with CLDN18.2-positive CRC. Design: Single-center retrospective study. Methods: A total of 805 patients who underwent surgical resection for pathological stage I–III CRC at the National Cancer Center Hospital (Tokyo, Japan) between 1997 and 2019 were identified. Expression of CLDN18.2 was evaluated by immunohistochemistry. The association of CLDN18.2 expression with clinicopathological features and treatment outcomes was assessed. The cutoff for CLDN18.2 positivity was defined as ⩾1%. Results: Among these patients, 17 (2.1%) had CLDN18.2-positive CRC. Right-sided CRC was significantly more common in patients who were CLDN18.2 positive than in those who were CLDN18.2 negative (76.5% vs 28.3%, p < 0.0001), as was mucinous or poorly differentiated adenocarcinoma (17.6% vs 3.0%; 17.6% vs 2.2%, p < 0.0001), T3–4 disease (100% vs 84.3%, p = 0.075), lymphatic invasion (64.7% vs 24.2%, p < 0.0001), BRAF V600E mutation (29.4% vs 4.1%, p < 0.0001), and deficient mismatch repair (MMR) status (47.1% vs 10.0%, p < 0.0001). Multivariate analysis did not identify CLDN18.2 expression status to be an independent predictor of relapse-free survival (RFS) or overall survival (OS). Conclusion: Approximately 2% of all CRC cases in this study were CLDN18.2 positive and had unfavorable features (e.g., mucinous or poorly differentiated adenocarcinoma, T3–4 disease, lymphatic invasion, BRAF V600E mutation) and deficient MMR status. CLDN18.2 positivity did not have a significant impact on RFS or OS.