Distribution of estrogen receptor subtypes, expression of their variant forms, and clinicopathological characteristics of human colorectal cancer.

We examined the expression of estrogen receptor (ER) messenger RNAs (ER-alpha, ER-beta, and ER-beta isoforms) in colorectal tumor samples and corresponding normal mucosa, paying particular attention exons 3 and 5 of both ER mRNA subtypes that likely suffer deletions, and may encode proteins that have lost either DNA- or ligand-binding moieties. Then we correlated these findings with the clinicopathological properties of the tumors. Our results demonstrated that in all patients the two ER subtype mRNAs were coexpressed in wild-type form. In 10% of the patients the ER-alpha mRNA was also present as an exon-5-deleted form that encoded any aberrant protein. Immunohistochemical analysis revealed that the ER-beta protein was present in tumor stroma, but not in infiltrating lymphocytes. ER-beta1 and ER-beta2, isoforms of ER-beta, were up-regulated in malignant tissues, whereas the ER-beta5 isoform, was found to be equally expressed, at very low levels, in the two tissue compartments. No correlations between ER levels and clinicopathological parameters were found. This suggests that the ER-beta mRNA levels are independent of the tumor characteristics.