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The Expression of Claudin-1, Claudin-2, Claudin-3, and Claudin-4 in Gastric Cancer Tissue

Hun Jung, M.D., Kyong Hwa Jun, M.D., Ph.D.Corresponding Author Informationemail address, Ji Han Jung, M.D., Ph.D., Hyung Min Chin, M.D., Ph.D., Woo Bae Park, M.D., Ph.D.

Received 31 December 2009 published online 08 March 2010.
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Background

The claudins (CLDNs) are a family of functional tight junction proteins, and are involved with the epithelial-to-mesenchymal transition (EMT). The claudin proteins have a significant influence on the biological behavior of tumor progression in several types of cancers. In this study, we aimed to evaluate the expression pattern of claudin-1, claudin-2, claudin-3, and claudin-4 in gastric cancer tissue.

Materials and methods

Tissue was obtained from surgically resected specimens of 72 patients who were diagnosed with gastric adenocarcinoma at a single institution. The expressions of claudin-1, claudin-2, claudin-3, and claudin-4 were determined by immunohistochemical staining with the ABC method.

Results

Claudin-2 demonstrated the highest expression rate (73.6%) and claudin-4 demonstrated the lowest expression rate (44.4%). The expression of claudin-1 was significantly lower in cases of intestinal type adenocarcinoma based on the Lauren classification. The expressions of claudin-3 and claudin-4 were significantly lower in cases with positive lymphatic invasion. The expression of claudin-3 was significantly lower in cases with an advanced T-stage (T3 and T4). The expression of claudin-3 showed significantly positive correlations with the expression of the other claudin proteins. In survival analysis, the expression of claudin-4 was related to good overall survival rate with significance (P = 0.046).

Conclusion

We suggest that claudin-3 and claudin-4 represent useful molecular markers for gastric cancer. Claudin-3 and claudin-4 would be the most important proteins related to the lymphatic invasion process, and claudin-4 would be useful with prognostic marker based on our results. Further investigations with a greater number of subjects are required to identify the action mechanism of claudin in gastric cancer.

 Department of Surgery, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea

 Department of Surgery, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea, Suwon, Korea

 Department of Pathology, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea, Suwon, Korea

Corresponding Author InformationTo whom correspondence and reprint requests should be addressed at Department of Surgery, St. Vincent's Hospital, The Catholic University of Korea, Ji-dong, Paldal-gu, Suwon, Gyeonggi-do, 442-723 Republic of Korea.

PII: S0022-4804(10)00106-X

doi:10.1016/j.jss.2010.02.010