gms | German Medical Science

The estrogen-related receptors (ERRa, ERRb, ERRg) display a high homology to classical estrogen receptors (ER) but do not bind natural estrogens. However, ERs and ERRs are functionally closely related and seem to control overlapping regulatory pathways such as proliferation of breast cancer cells. Further it was suggested that ERRa can serve as a prognostic marker which predicts a poor clinical outcome in breast carcinoma. To evaluate the role of ERRs in breast cancer we examined and correlated the expression of different receptors (ERRa, ERRg, ERa, PgR, c-erbB2) as well as transcriptional cofactors (AIB1, PGC1 and NCOR1) and ERR target genes (pS2, aromatase) using real-time quantitative PCR in unselected primary breast tumors (n=48). The mRNA profiles of the ERRs were compared to clinical and pathological parameters. In addition we determined ERR protein expression using immunohistochemistry on breast tumor tissue micro-arrays. About 50% of the samples showed higher ERRa and 27% ERRg mRNA expression levels compared to their overall mean expression. Elevated ERRa mRNA levels (median) could be seen in c-erbB2 positive tumors, in ki67 positive tumors, in older patients and patients with a breast cancer history in their family. The mRNA levels for ERRg were elevated in pT1, in pN0, in ki67-negative and in G1-2 tumors. Moderately elevated ERRg mRNA levels were found in ER-positive and in c-erbB2 negative tumors. The data indicate a possible predictive role for both receptors in breast carcinomas. Further univariate and multivariate analysis will be presented and the data will be discussed with respect to other published studies.