Co-expression of ER and c-erb B2 in breast cancer

Determination of the estrogen receptor (ER) status is done in the management of breast cancer as ER positive tumors have a favorable prognosis and are likely to respond to anti-estrogenic agents such as Tamoxifen (Tarn). However, ER positive tumors when treated with Tam may show innate or acquired resistance. In cell culture experiments, transfection of MCF-7 cells, an ER positive estrogen dependent breast cancer cell line, with c-erb-B2 expression vector results in Tam-resistance. Additionally, experimental data exists that shows that c-erb-b2 gene is transcriptionally repressed by estrogen stimulation, an effect reversed by tamoxifen. A strong relationship exists between c-erb-B2 positivity and ER negativity i.e. tumors that have escaped their dependence on estrogen for growth. A recent study based on microarray analysis has suggested the breast cancer can be sub-classified into mutually distinct groups based on ER and c-erbB2 expression. These in vitro data and clinical studies in human breast cancer have led to suggestions that c-erb B2 expression in ER positive tumors may be a marker of tamoxifen resistance. Methods: We retrospectively analyzed a series of 474 patients of breast cancer for expression of ER and c-erb B2. 77 cases had been reported as expressing both these biomarkers. These cases were reanalyzed and a representative set re-stained for both these markers using Dako's Dual staining kit. Results: Reexamination of these cases on serial sections IHC and by dual staining IHC showed co-expression of ER and c-erb b2 molecules in all the cases. In an individual case varying percentage of four distinct cell populations (ER+ c-erb b2-; ER- c-erb b2+; ER+ c-erb 2+; and both negative) and were identified. Conclusions: Human breast cancer is composed of mixed population of tumor cells that may or may not show expression of ER and c-erb b2. Co-expression of these molecules is seen in a percentage of cases (16.2%).