Distribution of the Mr 52,000 estrogen-regulated protein in benign breast diseases and other tissues by immunohistochemistry.

ABSTRACT

A secreted glycoprotein with a molecular weight of 52,000 is induced by estrogen in breast cancer cells and has been purified to prepare monoclonal antibodies. The protein has been detected in some breast cancers but not in normal breast and uterus. In order to study its potential value as a marker, we have tested by immunohistochemistry frozen sections of several normal and malignant tissues and of benign mastopathies. Among different tissues tested, the Mr 52,000 protein was detected only in liver, sweat glands, and some sebaceous glands, and in malignant melanomas and some breast tumors. Other estrogen-responsive tissues (ovary, placenta, endometrium, etc.) gave negative results. Immunoradiometric assay of the Mr 52,000 protein in biological fluid revealed an elevated concentration in cyst fluid (0.5 to 7.4 micrograms/ml), pleural effusions of certain metastatic breast cancer, and sweat. By immunohistochemistry, the Mr 52,000 antigen was also detected in 42% of 129 benign mastopathies. Gynecomastia, fibrous disease, fibroadenoma, and adenosis were mainly negative, whereas ductal hyperplasia and cysts were positive. The Mr 52,000 protein was found mostly in proliferative ducts and in cysts but not in lobular hyperplasia and nonproliferative lesions without cyst. More Mr 52,000 protein was found in postmenopausal patients than in premenopausal patients. We conclude that the Mr 52,000 protein is a marker associated with mammary cysts and proliferative ducts. On the basis of the increased risk of breast cancer in proliferative mastopathies, we suggest that the Mr 52,000 protein is useful for predicting high-risk mastopathies acting as a marker associated with the proliferation of ductal tissue.