Estrogen receptor alpha/beta, AIB1, and TIF2 in colorectal carcinogenesis: do coregulators have prognostic significance?

ABSTRACT

PURPOSE: Estrogen receptor beta (ER beta) is abundantly expressed in colorectal tissue, but its role in colorectal carcinogenesis remains elusive. Estrogen receptor coregulators, amplified in breast cancer 1 (AIB1) and transcription intermediary factor 2 (TIF2), have been well-characterized, but their expression in colorectal carcinomas has not been investigated. MATERIALS AND METHODS: Estrogen receptor alpha (ER alpha), ER beta, AIB1, and TIF2 protein expression were evaluated by immunohistochemistry in colorectal normal mucosa, adenomas, and adenocarcinomas from 110 patients with colorectal cancer. RESULTS: ER alpha expression was rare in colorectal tissue and its expression does not appear to be associated with colorectal carcinogenesis. ER beta, AIB1, and TIF2 were detected in the nucleus of epithelial, endothelial, inflammatory, smooth muscle cells, and myofibroblasts. The expression of the three proteins was significantly increased in epithelial cells of carcinomas compared to normal mucosa. In carcinomas, a significant correlation between the levels of expression of AIB1 and TIF2 was noted. Although AIB1 overexpression was associated with local tumor invasion, it was also found to correlate independently with prolonged overall survival. CONCLUSIONS: ER beta, AIB1, and TIF2 appear to be involved in colorectal tumorigenesis and might have prognostic significance.