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P065. Mucosal immune environment in colonic carcinogenesis: CD80 over‑expression in ulcerative colitis and dysplasia is associated to oxidative DNA damage and TLR4 expression

M. Scarpa1, R. Cardin2, M. Bortolami3, A. Kotsafti3, M. Scarpa3, A. Pozza3, G. Maran2, M. Picciocchi2, C. Ruffolo4, R. D'Incà3, I. Castagliuolo3, G.C. Sturniolo5, C. Castoro6, I. Angriman7

1University of Padua, Dip Scienze Chirurgiche e Gastroenterologiche Clinica Chirurgica I, Padua, Italy; 2University of Padua, Italy; 3University of Padua, Padua, Italy; 4Ospedale “Cà Foncello”, II Department of Surgery (IV Chirurgia), Treviso, Italy; 5University of Padua, Dip. Di Scienze Chirurgiche e Gastroenterologiche, Padua, Italy; 6Venetian Oncology Institute, Padua, Italy; 7University of Padua, Gastrointestinal and Surgical Sciences, Padua, Italy

Background: CD80 is up-regulated in UC with dysplasia suggesting that it may elicit an active role in the immunosurveillance mechanism. The aim of our study was to analyse the interplay between early events in colonic ulcerative colitis (UC)-related and non-inflammatory carcinogenesis and CD80 expression to clarify the stimuli of its up-regulation in UC and dysplasia.

Methods: Sixty-two patients affected with UC, UC with colonic dysplasia, UC and cancer, colonic adenoma, or colonic cancer and 11 healthy subjects were enrolled in our study. Tissue samples were taken from surgical specimens during colonic resection or during colonoscopy. Mucosal mRNA expression of TLR4 and NFkB was quantified with Real Time RT-PCR. TLR4, β-catenin and p53 expressions were analysed by immunohistochemistry. Mucosal levels of activated NFkB were measured with immunometric assays. Mucosal 8‑OHdG levels were measured by HPLC-ED. Non parametric tests were used for statistical analysis.

Results: In the UC carcinogenesis pathway, 8‑OHdG mucosal levels were higher in patients with UC and dysplasia compared to those in patients with UC (p = 0.03). CD80 mRNA mucosal levels directly correlated with 8‑OHdG mucosal levels (τ = 0.26, p = 0.04), TLR4 protein expression (τ = 0.45, p < 0.01) and with NFkB mRNA expression (τ = 0.24, p = 0.02). CD80 protein expression was directly correlated with 8‑OHdG mucosal levels (τ = 0.19, p = 0.05), and inversely correlated with TLR4 mRNA expression (τ = −0.25, p = 0.03).

Conclusions: Oxidative DNA damage peaked in UC-related dysplasia and it is directly correlated to CD80 expressiono. Moreover, the direct correlation of TLR4 protein expression and CD80 mRNA and the indirect correlation between CD80 protein expression and TLR4 mRNA expression that were observed may also be part of the immunosurveillance mechanisms. No significant correlations were observed with p53 and β‑catenin accumulation along the carcinogenesis.