IDENTIFICATION OF A CELL-SURFACE ANTIGEN (LEA.135) ASSOCIATED WITH FAVORABLE PROGNOSIS IN HUMAN BREAST-CANCER

The present study was undertaken with a rationale that loss of certain ''normal tissue'' antigens might have prognostic significance, reflec ting inactivation of the corresponding genes during neoplastic progres sion. An attempt was made to identify such antigens by means of genera ting monoclonal antibodies using a tolerization/immunization procedure . A monoclonal antibody generated by immunization of BALB/c mice with normal breast tissue extract, following prior tolerization with mammar y carcinoma cells, recognized a cell-surface glycoprotein, luminal epi thelial antigen, with an apparent molecular weight of 135,000 (LEA.135 ). The pattern of expression on LEA.135 was determined by immunohistoc hemical-staining techniques on frozen and formalin-fixed and paraffin- embedded tissue sections. LEA.135 was demonstrable on the apical plasm a membrane of normal and nonneoplastic epithelial cells in breast and other tissues. Studies have shown that LEA.135 is distinct from recept ors for epidermal growth factor and from known antigens associated wit h epithelial cells, including the family of keratins. In a retrospecti ve study, with a follow-up ranging from 5 to 15 years, patients whose breast tumor cells expressed LEA.135 had a superior overall survival r ate (78 0.139% at >5 years; P = 0.025). Furthermore, in patients with histologically poorly differentiated tumors, LEA.135-positive cases ha d a better prognosis (80 0.179% at >5 years; P = 0.013) compared with LEA.135-negative cases. In addition, in patients with aneuploid tumors , LEA.135-positive cases again showed an improved survival (90 0.001 % at >5 years; P = 0.039) compared with those that were with LEA.135 ne gative. The results suggest that the expression of LEA.135 provides a useful indication of clinical outcome in patients with breast carcinom as.