Claudins as biomarkers of differential diagnosis and prognosis of tumors.

Abstract

Claudins are a superfamily of transmembrane proteins, the optimal expression and localization of which are important for the normal physiological function of the epithelium and any imbalance may have pathological consequences. Not only insufficient but also excessive production of claudins in cancer cells, as well as their aberrant localization, equally manifest the formation of a malignant phenotype. Many works are distinguished by contradictory data, which demonstrate the action of the same claudins both in the role of tumor-growth suppressors and promoters in the same cancers. The most important possible causes of significant discrepancies in the results of the works are a considerable variability of sampling and the absence of a consistent approach both to the assessment of the immune reactivity of claudins and to the differential analysis of their subcellular localization. Combined, these drawbacks hinder the histological assessment of the link between claudins and tumor progression. In particular, ambiguous expression of claudins in breast cancer subtypes, revealed by various authors in immunohistochemical analysis, not only fails to facilitate the identification of the claudin-low molecular subtype but rather complicates these efforts. Research into the role of claudins in carcinogenesis has undoubtedly confirmed the potential value of this class of proteins as significant biomarkers in some cancer types; however, the immunohistochemical approach to the assessment of claudins still has limitations, needs standardization, and, to date, has not reached a diagnostic or a prognostic value.