ERβ expression in normal, adenomatous and carcinomatous tissues of patients with familial adenomatous polyposis

Abstract

Objectives. The APC gene mutation triggers familial adenomatous polyposis (FAP) and approximately 80% of sporadic colorectal cancers. FAP summarizes the natural history of colorectal cancer because low- and high-grade dysplastic lesions and adenocarcinoma are simultaneously present in the same patients free from individual and environmental variability factors. Estrogen receptor beta (ERβ) has recently been suggested as the most likely mediator of estrogen-related anti-carcinogenic effects in Apc^Min−/+ mice and humans. In this study we assessed the ERβ expression in the intestinal mucosa of FAP patients to verify its possible involvement in tumor progression in colorectal cancer. Material and methods. ERβ and ERα expression, cell proliferation (Ki-67) and apoptosis (TUNEL), were evaluated on archival biopsy material from six patients with FAP who underwent colectomy. Results. A progressive significant decrease of ERβ expression was observed in the different stages of the disease as compared to normal mucosa (p < 0.001). Interestingly, a decreased ERβ expression was directly correlated with apoptosis (r = 0.76, p < 0.001), and inversely correlated with cell proliferation (r = 0.54, p < 0.05). Conclusions. ERβ expression is related to the severity of the disease, supporting the role of ERβ as a relevant biomarker of tumor progression and possible chemopreventive target in patients at risk of colonic neoplasia.

Key Words::

• Colon cancer
• estrogen receptor
• familial adenomatous polyposis

Acknowledgements

This study was supported by Department (D.E.T.O.) funds and University of Bari funds. Author's contributions: B.M.: researched data for the article and wrote the paper; S.M.P.: researched data for the article, performed immunohistochemical studies and evaluated histological aspects; P.S.: researched data for the article, performed immunohistochemical studies and evaluated histological aspects; P.D.: contributed to the discussion of contents, histopathology evaluation and funds sources; G.R.: contributed to the discussion of contents and histopathology evaluation; D.L.M.: contributed to the discussion of contents, performed immunohistochemical studies and evaluated histological aspects; C.M.C.: contributed to the discussion of contents and the review of the manuscript before submission; D.L.A.: contributed to the discussion of contents, the review of the manuscript before submission and funds sources.

Declaration of interests: All authors have disclosed any financial and personal relationships with other people or organizations that could inappropriately influence (bias) their work, and declare that they have no conflicts of interest.