Carcinogenesis in Ulcerative Colitis: Immunosurveillance Mechanisms

Background The inconsistency between dysplasia rate and incidence of cancer in ulcerative colitis (UC)suggests the presence of an immunosurveillance mechanism. The aim of our study was to analyse the expression of costimulatory molecules CD80 and CD86, the lamina propria mononuclear cells populations and the cytokines network at the different stages of carcinogenesis in UC compared to the non inflammatory omologues. Patients and methods Five groups of patients affected by UC (19 pts), UC with colonic dysplasia (10 pts), UC and cancer (7 pts), colonic adenoma (11 pts), sporadic colonic cancer (15 pts) and a group of healthy control (11 pts) were enrolled. Mucosal CD80 and CD86 mRNA levels were quantified with Real Time PCR. Mucosal expression of CD80, CD86, CD3, CD20, CD68 and p53 was analysed by immunohistochemistry. Mucosal levels of IL-1β, IL-2 and TNF- α were measured with immunometric assays. Kruskal-Wallis ANOVA, Mann-Whitney U test and Kendall's tau correlation test were used. Results In UC, CD80 expression was higher in patients with dysplasia (p=0.017). This difference was not evident in the non inflammatory carcinogenesis (fig 1). CD80 expression directly correlated with IL-2 expression and with lamina propria T and B lymphocytes and monocytes populations. In UC, CD86 expression resulted significantly higher than in non inflammatory carcinogenesis without any differences between the steps of the carcinogenesis. CD86 expression correlated with inflammation severity and with IFNgamma expression. Conclusion In UC, CD80 is significantly more expressed in the dysplastic colonic tissue and it seems to be down regulated in cancer. CD80 mucosal levels correlate with T cell population and with IL-2 expression suggesting its involvement in the immunosurveillance mechanism in UC that prevent that all the dysplasia progress to cancer.