P053 Histological and immunohistochemical indicators of progression towards malignancy in ulcerative colitis
C. Popp*1, G. Micu1, M. Cioplea1, L. Sticlaru1, G. Pop1, B. Mateescu2, F. Staniceanu1, S. Zurac1, L. Nichita1
1Colentina University Hospital, Pathology, Bucuresti, Romania, 2Colentina University Hospital, Gastroenterology, Bucuresti, Romania
Ulcerative colitis (UC) is an inflammatory chronic bowel disease that increases the risk for carcinoma in patients with long evolution. Oxidative stress, because of inflammation, induces DNA damage in epithelial cells, leading to progressive dysplasia and, eventually carcinoma. This study characterises predysplasia histological and immunohistochemical markers, to identify patients prone to develop a malignancy.
We performed an observational prospective cohort study including 45 patients with UC. They were evaluated in the beginning of the study and after 12 months. All patients received adequate treatment according international and internal protocols. From each patient, multiple biopsies of normal and inflamed mucosa were taken for histopathological and immmunohistochemical diagnosis. Normal mucosa samples from 12 patients without UC (usually resection margins from sporadic bowel carcinomas) were used as control. For each sample, 3 independent pathologists evaluated parameters connected with evolution towards neoplasia: architectural distortion of the mucosa, and expression in epithelial cells of anti-apoptotic protein bcl-2, p53, and p21. Dysplasia was identified only on 1 biopsy from the second presentation.
Architectural distortion was identified in 42 patients at the first presentation and in all patients at the second presentation. In all cases, it worsened during the 12 months of the study, regardless of the clinical and endoscopical evolution. Evolution of architectural distortion was correlated with the presence of neutrophil granulocytes within colonic mucosa. bcl-2 was overexpressed in the majority of the samples with a significant decrease during the study. Overexpression of bcl-2 was concordant in epithelial cells and in lymphocytes, proving that both types of cells are affected by local oxidative stress. p53 and p21 had increased expression in the majority of samples, without significant increase during the study. Both correlated well with architectural distortion (t-test two-tailed p = 0.0251 for p53 and p = 0.0035 for p21).
Architectural distortion is an important indicator of evolution towards epithelial malignancy in UC, being a good surrogate for p53 and p21 mutations. In addition, bcl-2 expression is a good indicator of the effect on epithelial cells of oxidative stress. For patients with UC without dysplasia, architectural distortion can be used as indicator of evolution towards dysplasia, but evaluation of p53, p21, and bcl-2 is indicated, especially in patients with severe and persistent architectural distortion, to identify their risk of malignancy and establish a personalised surveillance schedule.