Еxpression of claudin-1, 3, and 4 in colorectal cancer and polyps

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Claudins are a family of transmembrane tight junctions proteins. It is proven that claudins undergo structural and functional alteration in malignant cells. However, very few researches are pursued on this topic, the data provided by different researchers are controversial. The aim of this study was to evaluate expression of tight junction proteins in cancer and benign polyps of the colon and rectum. Specimens of 32 colorectal adenocarcinomas and biopsy specimens of 86 polypoid lesions of the colon and rectum were selected from diagnostic material. Polyps were divided into 6 groups following the 2010 WHO classification of premalignant lesions of the colon and rectum. Immunohistochemical labeling with claudin-1, claudin-3 and claudin-4 antibodies was performed in all cases. We used G. Sheehan et al. (2007) method to evaluate the expression of claudins in neoplasm as well as in adjacent normal mucosa in each slide. Immunohistochemical staining with claudins antibodies had membranous pattern; claudins expression in adjacent normal mucosa was uniformly close to maximum. Serrated lesions showed the lowest level of expression of claudin-1 among other groups (p<0,05). In the group of adenocarcinomas we found moderate negative correlation between claudin-1 expression level and grade of adenocarcinoma. Claudin-3 expression level was significantly higher in adenocarcinomas compared to serrated lesions (p=0,025) and in conventional adenomas compared to serrated lesions (p=0,034). Expression of claudin-4 was strong in most cases, except for tubular adenomas that showed moderate expression in most cases. We found no statistically significant difference between levels of expression of claudin-1, claudin-3 and claudin-4 expression levels among adenocarcinomas, hyperplastic polyps, sessile serrated adenomas, traditional serrated adenomas, tubular and tubular-villous adenomas. But we detected significant difference after enlargement of the groups. This fact may argue for general development pathway of hyperplastic polyps and sessile serrated adenomas, and of tubular and tubular-villous adenomas. Expression of claudin-1 and claudin-3 revealed difference of serrated lesions from conventional adenomas and adenocarcinomas, that confirms conception of independent «serrated» pathway of cancerogenesis.