Altered expression of gamma-glutamyl transpeptidase in human tumors

Abstract

Elevated levels of gamma-glutamyl transpeptidase (GGT) activity and intracellular glutathione in tumor cells have been correlated with resistance to several classes of chemotherapeutic drugs. In this study, the first comprehensive analysis of GGT expression in human malignant neoplasms, 451 tumors were immunostained with an antibody directed against a c-terminus peptide of the human GGT protein. Analysis of the immunostaining revealed that GGT was expressed in 22 of 44 lung carcinomas and 16 of 22 ovarian surface epithelial carcinomas, although normal pulmonary and ovarian epithelium are GGT-negative. The tumor samples were obtained from patients before the start of therapy; therefore, GGT was not induced by radiation or chemotherapy. There was no GGT expression in mesotheliomas, Hodgkin's disease, non-Hodgkin's lymphomas, melanomas, basal cell carcinomas, and most soft tissue sarcomas, all of which are derived from GGT-negative cells. Carcinomas arising from some GGT-positive epithelium retained their GGT-positive phenotype. These included renal cell carcinomas, hepatocellular and cholangiocarcinomas, and carcinomas of the prostate and thyroid whereas both pancreatic adenocarcinomas and infiltrating carcinomas of the breast showed a wide range of GGT expression. Further studies are underway to determine whether expression of GGT plays a role in the inherent resistance of some tumors to alkylating agents and other classes of chemotherapeutic drugs.