Available online at www.sciencedirect.com Digestive and Liver Disease 40 (2008) 260–266 Alimentary Tract ER- expression in large bowel adenomas: Implications in colon carcinogenesis A. Di Leo a,∗,1 , M. Barone a,1 , E. Maiorano b , S. Tanzi a , D. Piscitelli b , S. Marangi a , K. Lofano a , E. Ierardi c , M. Principi a , A. Francavilla a a Section of Gastroenterology, Department of Emergency and Organ Transplantation (D.E.T.O.), Bari, Italy b Department of Pathologic Anatomy, University of Bari, Bari, Italy c Section of Gastroenterology, Department of Medical Science, University of Foggia, Italy Received 17 July 2007; accepted 29 October 2007 Available online 18 December 2007 Abstract Background. A pivotal role of oestrogen receptor-beta has been suggested in colon carcinogenesis in humans. However, few data are available on oestrogen receptor-beta in colorectal pre-cancerous lesions. Aim. In the present study, we evaluated oestrogen receptor-beta expression and its possible correlation with proliferative activity and apoptosis in colorectal adenomas and normal colon tissue. Patients/methods. Adenomatous tissue from 25 patients with colonic polyps, and normal tissue from 25 controls were used. Oestrogen receptor-beta expression, colonocyte proliferation (expressed as PCNA positivity) and apoptosis were evaluated. Results. In adenomatous tissue, a significant reduction of oestrogen receptor-beta was observed compared to normal mucosa (10.1 ± 5.5% vs. 44.2 ± 13.7; p < 0.03), while the expression of oestrogen receptor-alpha remained unvaried. Cell proliferative activity significantly increased in adenomatous tissue compared to normal mucosa (59.3 ± 7.1 vs. 18.5 ± 8.8; p < 0.0001), doubling the PCNA/apoptosis ratio. An inverse correlation was found between oestrogen receptor-beta and PCNA expression in adenomas (r = -0.81), a datum confirmed by confocal microscopy evaluation. Conclusions. Our data demonstrate, for the first time, a significant reduction of oestrogen receptor-beta expression already in the pre- cancerous phase of colon carcinogenesis. This suggests a role of selective oestrogen receptor-beta agonists in the prevention of colorectal cancer. © 2007 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved. Keywords: Colorectal cancer; Oestrogens receptors; Polyps intestinal 1. Introduction There is evidence of the ability of oestrogens to modulate proliferative activity not only in the classic oestrogen- responsive tissues [1] but also in organs and/or cells of other apparatuses [2–5]. They exert their biological activity by binding with two type of receptors: oestrogen receptor-alpha ∗ Corresponding author at: Sezione di Gastroenterologia, D.E.T.O., Uni- versit` a degli Studi di Bari, Policlinico, piazza Giulio Cesare, 11, 70124 Bari, Italy. Tel.: +39 080 5478611; fax: +39 080 5592494. E-mail address: a.dileo@gastro.uniba.it (A. Di Leo). 1 Both authors equally contributed to the realization of this paper. (ER-), the prevalent form in the breast, bone, cardiovascu- lar tissue, urogenital tract and central nervous system, and oestrogen receptor-beta (ER-), the prevalent form in the gut [6,7]. In 1987, using radiolabelled oestradiol, we demonstrated, the presence of ERs in colorectal cancer showing that well differentiated forms express higher levels of ERs as compared to undifferentiated colorectal cancers [8]. Subsequently, we demonstrated by immunoenzymatic assay that ER levels are lower in neoplastic mucosa than in normal surrounding tis- sues and that polyamine (polycationic compounds normally implicated in cell proliferation) reach higher levels in ER- negative colorectal carcinomas as compared to ER-positive 1590-8658/$30 © 2007 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.dld.2007.10.018