Claudin 18.2 expression profile in primary tumors and their ovarian metastases: implications for targeted therapy

Abstract

Background: Claudin 18.2 (CLDN18.2), a tight junction protein predominantly expressed in the normal gastric epithelium, has recently emerged as a potential therapeutic target in various solid tumors. Despite growing interest, comprehensive data on CLDN18.2 expression across primary tumors from different organs and their corresponding metastatic lesions remain limited.

Methods: This study analyzed CLDN18.2 expression in 102 patients with primary adenocarcinomas from various organs and their corresponding ovarian metastatic carcinomas and in 81 cases of primary ovarian mucinous tumors using immunohistochemistry. We evaluated the association of CLDN18.2 expression with clinicopathologic features and survival outcomes.

Results: The highest CLDN18.2 positivity rate was observed in gastric adenocarcinomas (40%, 12/30), followed by cervical adenocarcinomas (20%, 1/5) and colorectal adenocarcinomas (4%, 2/50). Notably, primary ovarian mucinous tumors showed remarkably high expression rates, reaching 77% overall and 100% in mucinous borderline tumors. In contrast, adenocarcinomas of the appendix and breast lacked CLDN18 expression. While CLDN18.2 expression was generally maintained during metastasis, some variations in expression patterns were observed, particularly in gastric cancers (13%, 4/30). Our analysis found no significant correlation between CLDN18.2 expression and overall survival in the patient cohort.

Conclusion: The preserved expression of CLDN18.2 in metastatic tumors underscores its potential utility as a target for therapeutic approaches. Our findings emphasize the importance of evaluating CLDN18.2 status in both primary and metastatic tumors to refine therapeutic strategies.

Keywords: Adenocarcinoma; Human CLDN18 protein; Neoplasm metastasis; Ovarian neoplasms; Survival analysis; Therapeutics.

Fig. 1

Representative matched pairs illustrating conversion of CLDN18.2 expression. A through F Negative-to-positive conversion from stomach to ovarian metastasis; Case 35 with gastric primary of (2 + , 30%, A) and ovarian metastasis of (2 + , 80%, B), Case 36 with gastric primary of (1 + , 30%, C) and ovarian metastasis of (2 + , 80%, D), and Case 43 with gastric primary of (2 + , 40%, E) and ovarian metastasis of (3 + , 80%, F). (G and H) Positive-to-negative conversion from stomach to ovarian metastasis; Case 64 with gastric primary of (3 + , 80%, G) and ovarian metastasis of (2 + , 30%, H) (magnification × 200)

Fig. 2

Representative matched pairs illustrating conversion of CLDN18.2 expression. A through F Negative-to-positive conversion from primary tumor to ovarian metastasis; Case 40 with appendiceal primary of (0, 0%, A) and ovarian metastasis of (3 + , 90%, B), Case 154 with appendiceal primary of (2 + , 20%, C) and ovarian metastasis of (3 + , 80%, D), and Case 50 with uterine cervix primary of (2 + , 40%, E) and ovarian metastasis of (2 + , 80%, F). (G through J) Positive-to-negative conversion from primary tumor to ovarian metastasis; Case 38 with colorectal primary of (3 + , 80%, G) and ovarian metastasis of (1 + , 80%, H), and Case 145 with colorectal primary of (2 + , 80%, I) and ovarian metastasis of (2 + , 5%, J) (magnification × 200)

Fig. 3

Kaplan–Meier estimates of overall survival according to CLDN18 expression (A), lymph node metastasis (B), and lymphovascular invasion (C) in primary cancers with ovarian metastasis; and CLDN18 expression (D), pT stage (E), and lymphovascular invasion (F) in primary ovarian mucinous neoplasms