RELATION OF GLUTATHIONE-S-TRANSFERASE ALPHA-ISOFORM AND MU-ISOFORM TORESPONSE TO THERAPY IN HUMAN BREAST-CANCER

Glutathione S-transferase (GST) represents a multifunctional enzyme fa mily consisting of four known cytosolic isoforms (alpha, mu, pi, and P hi) that detoxify a variety of xenobiotic chemicals and may confer res istance to both chemotherapeutic drugs and carcinogens in various expe rimental models, GST-pi has already been extensively studied in clinic al specimens, including breast cancer, We studied the immunohistochemi cal distribution and relative immunopositivity of GST-alpha and GST-pi , based on a grading system for immunointensity, in samples of 51 neop lastic and 46 normal breast samples and 12 lymph node metastases from patients treated with intensive chemotherapy and bone marrow transplan t, In normal breast tissue, GST-alpha localized predominantly to the c ytoplasm of scattered cells lining the luminal aspects of the ducts. O ccasional cells showed both cytoplasmic and nuclear GST-alpha immunore activity, GST-mu was stained in myoepithelial cells preferentially as well as in occasional ductal cells (including apocrine epithelium), va scular smooth muscle, and plasma cells, GST-alpha and GST-mu were dete cted in 22 of 51 (43%) and 24 of 48 (50%) invasive cancers, respective ly, In paired samples of normal and malignant tissue from the same pat ient, GST-alpha immunostaining in cancers was significantly less inten se compared to that of normal breast tissue in 13 of 41 (32%) cases, N o such trend was found for GST-mu in paired samples, Neither GST-alpha nor GST-mu immunopositivity in tumor or nonneoplastic breast was foun d to correlate with relapse-free or overall survival in this clinical context; however, the apparent decreased expression of GST-alpha in ma lignant versus normal breast epithelial cells could have important imp lications in breast carcinogenesis.