Mucosal immune environment in colonic carcinogenesis: CD80 up-regulation in colonic dysplasia in ulcerative colitis.
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.


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 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.


CONCLUSIONS
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.
Dept. of Oncological Surgery, Veneto Oncological Institute (IOV-IRCCS), via Gattamelata 64, Padua, Italy. marcoscarpa73@yahoo.it
Marco
M
Scarpa
Marina
M
Bortolami
Attilio
A
Cecchetto
Diego
D
Faggian
Andromachi
A
Kotsafti
Cesare
C
Ruffolo
Filippo
F
Navaglia
Anna
A
Pozza
Renata
R
D'Incà
Mario
M
Plebani
Giacomo C
GC
Sturniolo
Imerio
I
Angriman
D018122:B7-1 Antigen; D051940:B7-2 Antigen / Q000378:metabolism; D003093:Colitis, Ulcerative / Q000276:immunology*; D003110:Colonic Neoplasms / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006801:Humans; D007118:Immunoassay; D007413:Intestinal Mucosa / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D011230:Precancerous Conditions / Q000276:immunology*; D012333:RNA, Messenger / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology; D015854:Up-Regulation
D018122:B7-1 Antigen; D051940:B7-2 Antigen; D016207:Cytokines; D012333:RNA, Messenger