TY - JOUR
T1 - Mucosal immune environment in colonic carcinogenesis
T2 - CD80 up-regulation in colonic dysplasia in ulcerative colitis
AU - Scarpa, Marco
AU - Bortolami, Marina
AU - Cecchetto, Attilio
AU - Faggian, Diego
AU - Kotsafti, Andromachi
AU - Ruffolo, Cesare
AU - Navaglia, Filippo
AU - Pozza, Anna
AU - D'Inc, Renata
AU - Plebani, Mario
AU - Sturniolo, Giacomo C.
AU - Angriman, Imerio
PY - 2011/3
Y1 - 2011/3
N2 - Background: In patients with ulcerative colitis (UC) the inconsistency between the rate of dysplasia and actual cancer incidence suggests the presence of an immunosurveillance mechanism. The aim of our study was to analyse the expression of CD80 and CD86 during the different stages of UC-associated and in non-inflammatory carcinogenesis. Patients and methods: Sixty-two patients affected with UC, UC with colonic dysplasia, UC and cancer, colonic adenoma, or colonic cancer and 11 healthy subjects were enroled in our study. Tissue samples were taken from surgical specimens during colonic resection or during colonoscopy. Mucosal mRNA expression of CD80 and CD86 was quantified with real time polymerase chain reaction (RT-PCR). CD80, CD86 and p53 expressions and lamina propria mononuclear cell populations (CD3, CD20 and CD68) were analysed by immunohistochemistry. Mucosal levels of IL-1β, IL-2 and IFN-γ were measured with immunometric assays. Results: Among UC patients, CD80 protein expression was higher in those with dysplasia (p = 0.017). In non-inflammatory carcinogenesis pathway CD80 protein and mRNA expressions were lower compared to the corresponding steps in the UC pathway. CD80 expression was directly correlated with the lamina propria mononuclear cell populations (T and B lymphocytes and monocytes). CD80 protein, but not CD80 mRNA, expression was significantly and directly correlated with IL-2 expression. Conclusion: CD80 resulted to be up-regulated in UC with dysplasia, while it was down-regulated in cancer. CD80 mucosal levels correlate with lamina propria T-cell and with IL-2 expression suggesting that it may elicit an active role in the immunosurveillance mechanism.
AB - Background: In patients with ulcerative colitis (UC) the inconsistency between the rate of dysplasia and actual cancer incidence suggests the presence of an immunosurveillance mechanism. The aim of our study was to analyse the expression of CD80 and CD86 during the different stages of UC-associated and in non-inflammatory carcinogenesis. Patients and methods: Sixty-two patients affected with UC, UC with colonic dysplasia, UC and cancer, colonic adenoma, or colonic cancer and 11 healthy subjects were enroled in our study. Tissue samples were taken from surgical specimens during colonic resection or during colonoscopy. Mucosal mRNA expression of CD80 and CD86 was quantified with real time polymerase chain reaction (RT-PCR). CD80, CD86 and p53 expressions and lamina propria mononuclear cell populations (CD3, CD20 and CD68) were analysed by immunohistochemistry. Mucosal levels of IL-1β, IL-2 and IFN-γ were measured with immunometric assays. Results: Among UC patients, CD80 protein expression was higher in those with dysplasia (p = 0.017). In non-inflammatory carcinogenesis pathway CD80 protein and mRNA expressions were lower compared to the corresponding steps in the UC pathway. CD80 expression was directly correlated with the lamina propria mononuclear cell populations (T and B lymphocytes and monocytes). CD80 protein, but not CD80 mRNA, expression was significantly and directly correlated with IL-2 expression. Conclusion: CD80 resulted to be up-regulated in UC with dysplasia, while it was down-regulated in cancer. CD80 mucosal levels correlate with lamina propria T-cell and with IL-2 expression suggesting that it may elicit an active role in the immunosurveillance mechanism.
KW - Colonic carcinogenesis
KW - Costimulatory molecules
KW - Immunosurveillance
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U2 - 10.1016/j.ejca.2010.10.010
DO - 10.1016/j.ejca.2010.10.010
M3 - Article
C2 - 21067914
AN - SCOPUS:79851513658
VL - 47
SP - 611
EP - 619
JO - European Journal of Cancer
JF - European Journal of Cancer
SN - 0959-8049
IS - 4
ER -