Human germ cell tumours: expression of gamma-glutamyl transpeptidase and sensitivity to cisplatin

Previous studies have shown that the enzyme gamma-glutamyl transpeptidase ( GGT) is essential for the nephrotoxicity of cisplatin, This study was desig ned to determine whether GGT activity is necessary for the therapeutic effe ct of the drug. The relationship between GGT expression and clinical respon se to platinum-based chemotherapy was examined in 41 human germ cell tumour s, Sections of formalin-fixed, paraffin-embedded tumours were immunohistoch emically stained with an antibody directed against human GGT. There was no expression of GGT in any of the 17 seminomas or four dysgerminomas; whereas , 12/12 ovarian yolk sac tumours and 4/4 embryonal carcinomas of the testis were GGT-positive, In stage I tumours fewer tumour cells expressed GGT tha n in later stage tumours. In four germ cell tumours of mixed histology, the seminomatous and dysgerminoma areas were GGT-negative while the areas of t he tumour with yolk sac or embryonal histology contained GGT-positive tumou r cells. The patients with seminomas or dysgerminomas who were treated with cisplatin-based chemotherapy, all had a complete response despite the abse nce of GGT expression in these tumours. Fifteen of the 16 patients with yol k sac or embryonal carcinomas received cisplatin-based chemotherapy followi ng surgery. Twelve had a complete response, while three failed to respond t o platinum-based therapy, There was no correlation between the level of GGT -expression and response to therapy in this group, Three of the four patien ts with tumours of mixed histology were treated with cisplatin-based therap y, and had a complete response, Therefore, expression of GGT is not necessa ry for the therapeutic effect of cisplatin in germ cell tumours, The result s from this study suggest that systemic inhibition of GGT would inhibit the nephrotoxic side-effect of cisplatin without interfering with its activity towards germ cell tumours.