Relationship of Estrogen and Progesterone Receptor Protein Levels in Carcinomatous and Adjacent Non-Neoplastic Epithelium of the Breast: A Histopathologic and Image Cytometric Study

Abstract

Background. Results of a previous study demonstrating a correlation between steroid hormone receptor concentrations in benign and tumor tissue in patients with breast carcinoma suggest that receptor levels in breast epithelium undergoing malignant transformation may play a role in determining the receptor levels in the resulting carcinoma. Data used in that study were derived from ligand binding assays and may reflect shortcomings inherent in this methodology, particularly the dilution of receptor proteins from benign and malignant epithelial cells by stromal components.

Methods. We performed a correlation study of steroid hormone receptor expression in benign and malignant breast epithelial cells using computerized image cytometry and histologic sections stained for estrogen (ER) and progesterone receptor (PR), avoiding the problems of contribution of stromal cells to the measurements and uncertainty about the histologic composition of the sample. Sections which contained both tumor and non-neoplastic breast elements were obtained from surgical specimens from 50 patients with breast carcinoma.

Results. Positive area (PA) scores for ER in benign and malignant epithelium showed direct correlation that was significant (r=0.46, p<0.001), whereas those for PR, although trended in the same direction, did not (r=0.17, p>0.2). PA levels for both receptor proteins were higher in benign breast epithelium with proliferative features, compared to non-proliferative benign epithelium, and in tumors when the associated benign tissue had proliferative changes, but neither of these differences were statistically significant, suggesting that the correlation of ER levels in benign and malignant epithelium was not simply a function of proliferative change.

Conclusion. Our results provide support for the concept that ER expression in breast carcinoma depends partially on epithelial cell receptor levels in the breast in which it arises, but not for the analogous hypothesis for PR. When costs and benefits of tamoxifen chemoprevention are weighed for a patient at risk for breast carcinoma, and when cyto- or histopathologic breast tissue specimens are available, it may be reasonable to include breast epithelial ER levels among the factors considered in making the treatment decision.