P043 Immunohistochemical expression of angio and lymphangiogenic factors in colonic mucosa of patients with inflammatory bowel disease.
P.M. Linares1, M. Chaparro1, A. Algaba2, I. Guerra2, F. Bermejo2, J.P. Gisbert*1
1Hospital Universitario de La Princesa, IIS-IP and CIBERehd, Gastroenterology Unit, Madrid, Spain, 2Hospital Universitario de Fuenlabrada, Gastroenterology Unit, Madrid, Spain
To evaluate the possible differences between inflammatory bowel disease (IBD) and non-IBD, and between ulcerative colitis (UC) and Crohn's disease (CD), in the expression of VEGFA, -C, -D, VEGFR1, -R2, -R3, PlGF, Ang1, Ang2 and Tie2 in colonic mucosa
Biopsies from patients with and without IBD that underwent to a colonoscopy by medical criteria were prospectively included and their mucosal samples studied by immunohistochemistry. VEGFA, -C, -D, -R1, -R2, -R3 and PlGF expression Results were graded as follows: (++) over 50% of the tissue cells were stained, (+) below 50%, and (-) completely negative. Ang1, Ang2 and Tie2 were assessed as the average density of five hot spots at a magnification of x40. Endoscopic activity was assessed by endoscopic Mayo Subscore (UC) and SES-CD (CD) indexes. Patients were classified in accordance with the Montreal classification. In cases with active disease, biopsies were taken from both endoscopically affected and non-affected mucosa
101 biopsies from 58 patients with IBD (36 UC and 22 CD) and 19 controls were included; 56% patients were male and 20% smokers. 64% of the patients did not have endoscopic activity, 16% had moderate, 14% mild and 6% severe activity. Expression and mean count of Ang1, Ang2, VEGFR2 (p<0.01), and VEGFC, -R1 and Tie2 were higher in samples from patients with UC compared to CD (p<0.05). In patients with CD, Ang1 mean count, and expression of VEGFC, -D, -R2, PlGF, and VEGFR3, were higher (p<0.05), and the rest of factors were lower, than in controls. Expression of Ang2 (p<0.05) and of all the studied factors were higher in active samples than in non-active CD; on the opposite, VEGFD and -R3 were lower. Expression of VEGFR1 and Tie2 were higher in patients under anti-TNF treatment than in those who were not (p<0.05). VEGFR1 and -R2 expressions were higher in patients with extraintestinal manifestations (p<0.05). In UC, expression of all factors were higher in patients with UC than in controls (p<0.05). Mean count and expression of Ang1, Ang2 were higher, and VEGFD was lower (p<0,05) in samples with active disease. Patients with smoking habit had a lower expression of VEGFR2 (p<0.05). Patients under 5-ASA treatment had a lower expression of VEGFD (p<0.05), and those under thiopurine treatment had a higher expression of VEGFA and PLGF (p<0.05) compared to untreated ones. VEGFR2 expression was higher in patients with left-sided colitis (p<0.05)
Angiogenic factors are differentially expressed at mucosal level in patients with CD and UC. Our findings might support a role of angiogenic factors in disease activity and behaviour of IBD. Expression of these factors in colonic mucosa of IBD patients may be modulated by immunosuppressive and anti-TNF treatment