Immunohistochemical Analysis of Estrogen Receptors in Breast Carcinomas Using Monoclonal Antibodies That Recognize Different Domains of the Receptor Molecule

Abstract

Estrogen receptor (ER) analysis was performed in 46 primary breast carcinomas using four monoclonal antibodies (MABs) to ER (AER311, ER1D5, LH1, and LH2), each of which recognizes a distinct domain of the receptor protein. ER was expressed as the percentage of positively stained tumor cells. Statistical analysis was performed using the SPSS/PC+ program to set the cut off of positivity and the prognostic value of each MAB. A positivity >30% for each MAB possessed the best sensitivity/specificity ratio and was used as the cut-off value. Multivariate discriminant analysis showed that MABs AER311, ER1D5, and LH2 had significant prognostic value. Fourteen tumors showed positivity for these three MABs; 17 were positive for one or two of the three MABs, and 15 were negative for all three MABs. Survival analysis showed that patients with tumors negative for all three of these MABs had progression of the disease within 8 years from the diagnosis of the tumor, whereas all patients with tumors positive for all three MABs were alive 13 years after surgery. A significant correlation (P = 0.0006) between tumor grading and ER status was found; 71% of the tumors that were positive for all three MABs were grade 1, whereas tumors negative for all three MABs were mostly grades 2 and 3. No significant relationship was observed between ER status and tumor size. A significant correlation (P = 0.008) between lymph node status and ER was found; breast tumors positive for all three MABs were in the majority (92.9%) of cases pNO, whereas 67% of tumors negative for all three MABs were pN1. Results from the present study suggest that the use of a panel of MABs that target distinct epitopes within domains of the ER protein could offer a better approach for assessing the ER status in breast cancer patients, because it enables the recognition of breast tumors with intact or structurally defective ER proteins.