HUMAN OVARIAN-TUMORS EXPRESS GAMMA-GLUTAMYL-TRANSPEPTIDASE

Gamma-glutamyl transpeptidase (GGT) is a cell surface enzyme that init iates the cleavage of extracellular glutathione, thereby providing the cell with the amino acids necessary for increased synthesis of glutat hione. GGT is induced in ovarian tumor cell lines selected in vitro fo r resistance to cisplatin. No study has examined GGT expression in pri mary human ovarian tumors. We analyzed frozen sections of 80 normal hu man ovaries and 56 ovarian tumors for expression of GGT. Histochemical staining showed that GGT was not expressed in the cells of the follic le or surface germinal epithelium of the normal ovary. GGT was express ed in some epithelial inclusion glands and occasionally in a small sub set of stromal cells. Granulosa-stromal cell tumors were largely GGT-n egative. In contrast, GGT-positive neoplastic cells were observed in 3 3 of 45 common epithelial ovarian tumors. None of the patients had bee n treated with chemotherapy. Some of the tumors had only rare GGT-posi tive cells, while others consisted almost entirely of GGT-positive cel ls. Among the low malignant potential and invasive tumors, at least on e-half of the cells were GGT-positive in 6 of 9 serous borderline tumo rs (2 with mucinous foci), 0 of 1 borderline mucinous tumor, 3 of 12 s erous papillary carcinomas, 2 of 3 mucinous carcinomas, 1 of 2 endomet rioid carcinomas, 2 of 2 clear cell carcinomas, 0 of 2 transitional ce ll carcinomas, and 4 of 5 undifferentiated carcinomas. There was no co rrelation between the stage of the tumor and GGT expression, indicatin g that a GGT-negative tumor does not become GGT-positive as it progres ses to a more widely disseminated lesion. In addition, there was no co rrelation between serum levels of CA 125 and GGT expression. These dat a show that GGT is expressed in many common ovarian epithelial neoplas ms. We are currently following the response of these patients to chemo therapy to determine if expression of GGT serves as a marker for ident ifying neoplasms with enhanced resistance to platinum-based therapy.