Altered expression of gamma-glutamyl transpeptidase in human tumors

Elevated levels of gamma-glutamyl transpeptidase (GGT) activity and intrace llular glutathione in tumor cells have been correlated with resistance to s everal classes of chemotherapeutic drugs. In this study, the first comprehe nsive analysis of GGT expression in human malignant neoplasms, 451 tumors w ere immunostained with an antibody directed against a c-terminus peptide of the human GGT protein. Analysis of the immunostaining revealed that GGT wa s expressed in 22 of 44 lung carcinomas and 16 of 22 ovarian surface epithe lial carcinomas, although normal pulmonary and ovarian epithelium are GGT-n egative. 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 l ymphomas, melanomas, basal cell carcinomas, and most soft tissue sarcomas, all of which are derived from GGT-negative cells. Carcinomas arising from s ome GGT-positive epithelium retained their GGT-positive phenotype. These in cluded renal cell carcinomas, hepatocellular and cholangiocarcinomas, and c arcinomas of the prostate and thyroid whereas both pancreatic adenocarcinom as and infiltrating carcinomas of the breast showed a wide range of GGT exp ression. Further studies are underway to determine whether expression of GG T plays a role in the inherent resistance of some tumors to alkylating agen ts and other classes of chemotherapeutic drugs. HUM PATHOL 30:300-305. Copy right (C) 1999 by W.B. Saunders Company.