Differential Expression of Claudin-1, Claudin-3, and Claudin-4 in Bladder Lesions

Abstract

Aims: Claudins are major transmembrane proteins of tight junctions. As the disruption of their function have important impact on tumorogenesis, invasion and metastasis. Claudins became a focus of interest for targeting therapies. Although their expression profiles have been studied in many organs, researches on Claudin expression in bladder are in limited number. The aim of this study is to present the differential expression of Claudin-1, Claudin-3 and Claudin-4 in invasive and noninvasive urothelial lesions. Study of Design: Several groups of noninvasive and invasive urothelial lesions were stained immunohistochemically by Claudin-1, Claudin-3 and Claudin-4 and their expressions were evaluated.  Place and Duration of Study: Department of Pathology of Diskapi Research and Training Hospital, Ankara, between 2011-2013. Methodology: 83 cases (31 invasive urothelial carcinomas (IUCC) –further divided into: 15 muscle invasive UCCs, 16 UCCs with lamina propria invasion-, 17 noninvasive papillary urothelial carcinomas (NPUC), 13 papillary urothelial neoplasms of low malignant potential (PUNLMP), 7 carcinoma in situ (CIS) and 15 normal independent samples (CG). Sections from formalin-fixed paraffin embedded tissues were immunohistochemically stained with Claudin 1, Claudin 3 and Claudin 4. Results: Claudin-1 expression is significantly lower in low grade noninvasive urotelial carcinomas compared to invasive carcinomas. Claudin-3 is highly expressed in normal urothelium and invasive lesions; but its expression is decreased significantly in all non-invasive lesions. Claudin-4 expression appeared to decrease in muscle invasive UCC and CIS vs. others. Conclusion: Although higher expression of Claudin-4 in low-grade and non-invasive lesions may be used as a diagnostic tool, decreased expression of Claudin-4 can indicate more invasive capacity of the tumour. In terms of Claudin-1 and -3, their decreased expression in non-invasive lesions when compared to control group and their trend to show more increased expression in IUCC needs to be studied further in larger studies.