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Expressions of Cell Junction Regulatory Proteins and Their Association With Clinicopathologic Parameters in Benign and Malignant Gallbladder Lesions

Cell junction regulatory proteins such as claudin-1, occludin, E-cadherin and snail play an important role in modulation of human cancer development. This study assessed the association of the expression of these proteins in lesions of gallbladder with clinicopathologic data. Tissue sections from adenocarcinoma, peritumoral tissues, adenomatous polyp and chronic cholecystitis were immunohistochemically analyzed for expression of claudin-1, occludin, E-cadherin and snail proteins. Expression of claudin-1, occludin and E-cadherin was significantly lower in adenocarcinoma than in peritumoral tissues, adenomatous polyp or chronic cholecystitis. Expression of snail was significantly higher in adenocarcinoma than in peritumoral tissues, adenomatous polyp or chronic cholecystitis. Furthermore, expression of claudin-1, occludin and E-cadherin was significantly higher in well-differentiated adenocarcinoma, defined by a maximal tumor size <2 cm with neither lymph node metastasis nor invasion to the regional tissues, than those in poorly differentiated adenocarcinoma with a maximal tumor size ≥2 cm, lymph node metastasis and such invasion. Expression of snail was in reverse association. Patients with expression of claudin-1, occludin-1 and E-cadherin survived longer than the patients without these proteins, but patients with snail expression died earlier than those who did not. Cox multivariate regression analysis showed the characteristics of poorly differentiated adenocarcinoma (tumor size ≥2 cm, lymph node metastasis and tumor invasion to the regional tissues) were poor-prognostic factors negatively correlated with postoperative survival. Expression of claudin-1, occludin-1 and E-cadherin were favorable-prognostic factors. Snail expression, which was a poor-prognostic factor, was negatively correlated with postoperative survival.