771P - Claudin-6 expression in primary and recurrent epithelial ovarian cancer: A potential therapeutic target for high-grade serous ovarian cancer

Background

Claudin (CLDN) comprises 27 family members, with the majority involved in tight junctions and cell-to-cell adhesion, playing a significant role in cancer initiation and progression. Targeting CLDNs has recently garnered attention as a potential avenue for new cancer therapies, demonstrating antitumor activity. However, limited data are available regarding the frequency of CLDN6 expression and its relationship to clinical factors in epithelial ovarian cancer (EOC).

Methods

We performed immunohistochemical (IHC) staining for CLDN6 expression on a total of 232 EOC surgical samples (including 181 primary and 52 recurrent tumors) and 49 ascites cell blocks. CLDN6 IHC was conducted using the Leica BONDIII staining platform with the anti-CLDN6 antibody. The CLDN6 IHC scoring followed the HER2 detection guidelines for gastric cancer (0, 1+, 2+, 3+), with a score of ≥1+ intensity in ≥10% of tumor cells considered positive.

Results

We investigated 181 patients with primary EOC for CLDN6 expression through IHC. Among them, 63 (34.8%) patients tested positive. CLDN6 expression was more frequent in high-grade serous carcinomas (54.4%, p < 0.0001), stage III/IV tumors (52.8%, p < 0.0001). CLDN6-positive patients showed shorter PFS and OS (p < 0.0001 and p = 0.020) compared to CLDN6-negative patients. We also assessed CLDN6 expression in 52 tumors at the time of recurrence. 15 of 52 (28.8%) recurrent tumors tested positive for CLDN6 expression. CLDN6 expression in recurrent tumors was observed in 10/24 (41.6%) high-grade serous, 2/19 (10.5%) clear cell, and 1/4 (25.0%) endometrioid cases. Furthermore, we examined CLDN6 expression in ascites cells and found that 16/27 (59.3%) from primary and 7/22 (31.8%) from recurrent EOC tested positive for CLDN6 expression.

Conclusions

CLDN6 expression is observed in both primary and recurrent EOC tumors of all histotypes, with a higher prevalence in high-grade serous carcinoma. The frequency of CLDN6 expression remains consistent between primary and recurrent tumors. These findings highlight CLDN6 as a promising therapeutic target for high-grade serous ovarian cancer.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.