The prognostic significance of steroid receptor co-regulators in breast cancer: co-repressor NCOR2/SMRT is an independent indicator of poor outcome
The assessment of the estrogen receptor (ER) alpha and the progesterone receptor (PgR) in breast cancer tissues is important for discriminating between hormone-dependent and hormone-independent tumors. ERbeta, a more recently discovered ER, may influence estrogen action through the ERalpha pathway. To evaluate the clinical significance of these receptors in the response to endocrine therapy, we investigated their expression in primary breast cancer tissues. ERalpha and PgR were evaluated using immunohistochemistry (IHC) and enzyme immunoassay (EIA) and ERbeta expression was determined using IHC and reverse transcription-polymerase chain reaction. When the cut-off level of EIA was set at 13 fmol/mg protein for ERalpha and that for IHC was set as an IHC score between 2 and 3, a significant correlation between ERalpha EIA and IHC was seen (concordance rate 88.4%). This indicates that this cut-off level of ERalpha IHC can be adopted to quantify breast cancer prognoses. Furthermore, the tumors with positive expression of ERalpha IHC or PgR IHC using this criterion were significantly related to the response to endocrine therapy. Additionally, tumors with positive expression of ERbeta wild-type tended to have a better response to endocrine therapy than negative ones, and tamoxifen responders tended to exhibit a lower ratio of ERbetacx (one of the ERbeta variants) to ERbeta wild-type than nonresponders. The results concerning ERbeta are not yet fully understood; further investigations and evaluations should analyze the role of ERbeta wild-type and variant type in breast cancer treatment.