Observations on the presence of E domain variants of estrogen receptor-alpha in the breast tumors.

摘要

BACKGROUND AND OBJECTIVES: Estrogen receptor-alpha (ER-alpha) that exists as multiple splice variants, has been widely used as a prognostic marker in the management of breast cancer. Here we have analyzed the hormone binding E domain splice variants of ER-alpha in the breast tumors with reference to the immunoreactive receptor. METHODS: Thirty breast cancer patients undergoing surgery at the All India Institute of Medical Sciences, New Delhi, were analyzed for the splice variants of E domain by RT-PCR. The ER level was determined by ELISA and the samples were considered positive if the receptor levels were >or= 15 fmol/mg protein. RESULTS: Our results show that exon 4 and 5 deletions were prevalent in both ER-positive and ER-negative categories. While most ER-positive cases expressed wild-type (wt) exon 6 + 7, nearly 40% of ER-negative cases showed deletion of exon 6 + 7. Therefore, deletion of exon 6 + 7 or masking of epitopes could lead to underestimation of ER by ELISA. All the metastasis and recurrence cases had undetectable levels of ER. A significant number of node-positive cases expressed immunoreactive ER and wt exon 6 + 7 (r = 0.509, P < 0.37). CONCLUSIONS: Estimation of ER levels combined with composite analysis of ER variants may be a better prognostic marker for breast cancer.