Tight junction disruption via claudin-6 overexpression promotes invasion and recurrence in high-grade endometrial tumors

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BACKGROUND Claudin-6 (CLDN6), a tight junction protein typically restricted to embryonic tissues, is re-expressed in various cancers. However, its prognostic significance in high-grade endometrial carcinoma (HGEC) remains unclear. AIM To investigate the expression pattern of CLDN6 in HGEC and assess its correlation with clinicopathological parameters and patient survival. METHODS Immunohistochemical analysis of CLDN6 expression was performed on formalin-fixed, paraffin-embedded tissues from 80 patients diagnosed with HGEC. Associations between CLDN6 expression and histological subtype, the International Federation of Gynecology and Obstetrics (FIGO) stage, depth of myometrial invasion, lymphovascular space invasion, recurrence, and survival outcomes were statistically analysed. Univariate and multivariate Cox regression models were used to identify independent prognostic factors. RESULTS High CLDN6 expression was detected in a subset of HGEC patients and was significantly associated with nonendometrioid histology (P = 0.026), advanced FIGO stage (P = 0.015), deep myometrial invasion (P = 0.038), and recurrence (P = 0.002). While Kaplan-Meier analysis did not reveal a statistically significant difference in disease-free survival or overall survival between the high CLDN6 expression group and the low CLDN6 expression group, multivariate Cox regression revealed that CLDN6 overexpression was an independent predictor of shorter disease-free survival [hazard ratio (HR) = 68.98, P = 0.022] and overall survival (HR = 24.023, P = 0.038). CONCLUSION CLDN6 overexpression is associated with aggressive tumor features and poor clinical outcomes in HGEC, suggesting its utility as a prognostic biomarker and potential therapeutic target.