Identification of claudin-2, -6, -11 and -14 as prognostic markers in human breast carcinoma.

The development of cancer occurs with various genomic and epigenetic modifications that act as indicators for early diagnosis and treatment. Recent data have shown that the abnormal expression of the claudin (CLDN) tight junction (TJ) proteins is involved in the tumorigenesis of numerous human cancers. Real-time quantitative PCR and western blotting were used to explore the differences in the expression of the CLDN TJ proteins in breast carcinoma tissues and non-neoplastic tissues. The results showed that CLDN5, CLDN9, CLDN12 and CLDN13 were not expressed in breast carcinoma tissues or non-neoplastic tissues. CLDN1, CLDN3, CLDN8 and CLDN10 were expressed in breast carcinoma and non-neoplastic tissues, but there was no significant difference between the expression of these CLDN proteins among them. The expression of CLDN2, -6, -11 and -14 varied between the breast carcinoma and non-neoplastic tissues. Moreover, 86 samples of breast carcinoma and non-neoplastic tissues were examined for the expression of CLDN2, -6, -11 and -14 by streptavidin-peroxidase immunohistochemical staining. The data revealed that the CLDN2, CLDN6, and CLDN14 were expressed in the cell membrane and the expression levels of these proteins were downregulated in breast carcinoma. The CLDN11 was expressed in cell cytoplasm and the expression level of CLDN11 was upregulated compared with those in non-neoplastic tissues. Consistent with these findings, the expression of CLDN2, CLDN6 and CLDN14 were downregulated, while the expression of CLDN11 was upregulated in breast carcinoma compared with those in non-neoplastic tissues. Furthermore, the associations between these CLDNs and clinicopathologic indicators were analyzed, and these CLDN expressions were revealed to be associated with distant metastasis and to predict a poor prognosis. In conclusion, our data showed that the expression levels of CLDN2, -6, -11 and -14 differed between breast carcinoma tissues and histologically non-neoplastic tissues, and the expression levels of these CLDNs may be useful as molecular markers for the diagnosis of breast carcinoma as well as for the determination of metastasis and prognosis.