Identification of a Cell-Surface Antigen (LEA.135) Associated with Favorable Prognosis in Human Breast Cancer

Abstract

The present study was undertaken with a rationale that loss of certain “normal tissue” antigens might have prognostic significance, reflecting inactivation of the corresponding genes during neoplastic progression. An attempt was made to identify such antigens by means of generating monocional 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 mammary carcinoma cells, recognized a cell-surface glycoprotein, luminal epithelial antigen, with an apparent molecular weight of 135,000 (LEA.135). The pattern of expression on LEA.135 was determined by immunohistochemical-staining techniques on frozen and formalin-fixed and paraffin-embedded tissue sections. LEA.135 was demonstrable on the apical plasma membrane of normal and nonneoplastic epithelial cells in breast and other tissues. Studies have shown that LEA.135 is distinct from receptors for epidermal growth factor and from known antigens associated with epithelial cells, including the family of keratins. In a retrospective study, with a follow-up ranging from 5 to 15 years, patients whose breast tumor cells expressed LEA.135 had a superior overall survival rate (78 0.139% at >5 years; P = 0.025). Furthermore, in patients with histologically poorly differentiated tumors, LEA.135-positive cases had 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 negative. The results suggest that the expression of LEA.135 provides a useful indication of clinical outcome in patients with breast carcinomas.