P013. The fall of estrogen receptors expression in long-lasting ulcerative-associated carcinoma
M. Principi1, M.P. Scavo1, D. Piscitelli1, V. Villanacci2, A. Contaldo1, V. Neve1, K. Lofano1, G. Piacentino1, N. De Tullio1, E. Ierardi3, A. Di Leo1, 2University of Bari, Bari, 2Spedali Civili, Brescia, 3University of Foggia, Italy
Colo-rectal carcinoma (CRC) is the most important cause of death in Inflammatory Bowel Diseases (IBD). Long lasting disease is one of the negative prognostic factors for CRC in IBD. The relationship between cancer progression and ERs expression has been diffusely investigated: ERs exhibit tissue specific expression in some tumors. We have, already, observed, in intestinal adenomatous polyps samples likewise, in Familial Adenomatous Polyposis (FAP), a significant reduction in ER-beta expression compared to normal colonic mucosa. In long-lasting pancolitis with low-grade dysplasia ER-beta level was only slightly reduced without changes in ER-alpha expression.
Our primary endpoint was to identify ER-beta/alpha expression in long lasting pancolitis in each stage as far carcinoma; secondary endpoint was to investigate simultaneously apoptosis and cell proliferation.
Twenty patients, affected by long lasting pancolitis in clinical remission were retrospectively enrolled. Disease history was >10 years in all. Four normal colon samples were taken as controls. Samples were divided into three groups: eight UC without (UC) and four with low-grade dysplasia (UC-dysplasia) and eight with carcinoma (UC-carcinoma). ER-beta and ER-alpha expression, Ki-67 and Tunel were evaluated by immunohystochemical methods.
ER-beta, ER-alpha expression and their ratio, assessed in normal mucosa, in UC and in UC-dysplasia, did not show significant changes while in UC-carcinoma revealed a dramatic fall of ER-beta expression (p < 0.01) and still more ER-beta/ER-alpha (p < 0.005). Apoptosis and Tunel/Ki-67 ratio demonstrated a statistically significant progressive increase from UC to UC-carcinoma through UC-dysplasia.
Our experience assessed modifications of ERs expression, apoptosis and cell proliferation in dysplasia-carcinoma sequence in the course of UC. We observed a dramatic fall of ER-beta, ER-beta/ER-alpha and a progressive increase of apoptosis in progressive steps from long-lasting UC to UC-carcinoma. As observed in adenoma model, the ER-beta drop could be a biomarker of dysplasia progression and a relevant point in the study of carcinogenesis in the course of UC. Further studies are warranted.