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

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 ApcMin−/+ 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.