DISTRIBUTION OF GLUTATHIONE-S-TRANSFERASE ISOENZYMES IN PRIMARY EPITHELIAL TUMORS OF THE OVARY

The glutathione S-transferases play a central role in the detoxification of electrophilic xenobiotics, including cytotoxic drugs and carcinogens, by conjugation with reduced glutathione. There are four major classes of human GST:pi, alpha, mu and microsomal GST. GST pi has been implicated in the progression of carcinogenesis in both animal and human studies. This study examined constitutive GST isoenzyme expression in 60 primary epithelial tumors of the ovary, including benign, borderline and frankly malignant categories. GST pi was the predominant isoenzyme, being strongly expressed in all tumor types. The intensity of GST pi staining was independent of grade in all categories of carcinoma. Thus GST pi has no potential role as a marker of differentiation or tumor progression in epithelial ovarian tumors. GST alpha, which localizes to steroid-producing cells in normal ovary, was useful in demonstrating enzymatically active stromal cells in ovarian carcinomas with functioning stroma. GSTs, particularly the alpha and microsomal isoenzymes, have been implicated in both intrinsic and acquired resistance to cancer chemotherapy. Alpha, mu and microsomal GSTs displayed a heterogeneous staining pattern in all tumor types. This heterogeneity of expression may contribute to intrinsic drug resistance in ovarian carcinomas.