The role of gamma-glutamyltransferase in malignant transformation and prognosis of ovarian cancer.

Abstract

e16524 Background: Gamma-glutamyltransferase (GGT) – a membrane bound enzyme crucially involved in the cell’s detoxification pathway and apoptotic balance – is involved in tumor development, progression and chemotherapy resistance. Elevated GGT serum levels are associated with increased cancer risk in women and worse prognosis in gynecologic cancers. The present study investigated the prognostic role of GGT in ovarian cancer patients. Methods: In this multi-center study, pre-therapeutic GGT levels were ascertained in 634 consecutive patients with epithelial ovarian cancer (EOC, n = 567) and borderline tumor of the ovary (BTO, n = 67). GGT serum levels were associated with clinico-pathological parameters and uni- and multivariate survival analyses were performed.Immunohistochemistry of GGT was performed in ovarian cancer tissue and correlated with GGT serum levels. Results: Pre-therapeutic GGT serum levels were higher in patients with EOC (28.56 [38.24] U/L) than in patients with BTO (20.01 [12.78] U/L, p = 0.01). High GGT serum levels were associated with advanced FIGO stage (p<0.001) and with worse overall survival in univariate (p < 0.001) and multivariable analysis (p=0.02, HR 1.2 [1.1-1.5]). We further investigated the association between systemic GGT serum levels and local GGT expression in EOC tumor tissue and observed an association between these two parameters (p = 0.03). Conclusions: High pre-therapeutic GGT serum levels are associated with advanced tumor stage and serve as an independent prognostic marker for worse overall survival in patients with EOC. GGT expression in ovarian cancer tissue is reflected in GGT serum levels.