Decreased Expression of Claudin 1, 3, 4, 5 and 7: A New Prognostic Marker in Colon Carcinoma

Background and objective: Claudins are members of a large family of tissue specific adherent proteins which have been suggested as tumor markers. In this study we analyzed the protein expression of claudin 1, 3, 4, 5 and 7, their clinical significance and association with tumor growth pattern in colon carcinoma. Methods: Immunohistochemical staining (IHC) was used to detect the expression of claudin 1, 3, 4, 5 and 7 in samples diagnosed with colon carcinoma as well as the adjacent normal mucosa. Complexity index (CI) was calculated using images of cytokeratin-8 stained slides of the tumours using Photoshop CS, Fovea Pro, and Image J computer programs. The results from the IHC and CI were correlated to clinicopathological parameters as well as 5-years survival of the patients diagnosed with colon carcinoma. Results: Significantly high staining intensity was observed in normal mucosa as compared to colon cancer tissue for claudin 4 (p=0.031) and 7 (p=0.011) and number of stained cells for claudin 4 (p=0.001). A significant association was also observed between weaker expression at the invasive front of the tumor tissue and heterogenous expression of claudin 1 (p=0.000), claudin 3(p=0.003), claudin 5(p=0.001) and claudin 7(p=0.000). There was no significant correlation between the expression of claudins, CI and clinicopathological parameters. Similarly, no significant association was found between claudin expression and 5-year survival of the patients diagnosed with colon carcinoma. Conclusion: Altered expression of claudin 1, 3, 4, 5 and 7 in colon carcinoma cells may play a promoting role in colon carcinoma development and is inversely proportional to higher expression at the invasive front of the tumor. Claudin protein expression can be used as a tumor marker since the expression generally is weaker in tumor tissue compared to the normal mucosa. Page 2 of 6 Citation: Ahmad A, Befekadu R, Askari S, Strömberg VH (2016) Decreased Expression of Claudin 1, 3, 4, 5 and 7: A New Prognostic Marker in Colon Carcinoma. J Gastrointest Cancer Stromal Tumor 1: 105. doi:10.4172/jgcst.1000105 Volume 1 • Issue 1 • 1000105 J Gastrointest Cancer Stromal Tumor ISSN: JGCST, an open access journal while tumors with 5 CI score have highly irregular invasive front with separated tumor cells and clusters [17]. This classification was based upon the fractal dimensions, and number of tumor cells. The proteins, which are involved in the intercellular adhesions are important in maintaining the morphology of the tumor and affect the invasion and metastasis [18,19]. Being a part of tight junction complex, claudins have a significant role in cell adhesion [20]. So we hypothesize that there is a correlation between tumor progression, tumor growth pattern and adhesive protein expression. The aim of our study was to compare the expression patterns of 5 different claudin proteins (claudin 1,3,4,5 and 7) in normal and paired human colon carcinoma tissue samples and to correlate these results with 5-year survival data of the patients, growth pattern of tumor and clinicopathological parameters of the patients diagnosed with colon carcinoma. Material and Methods