Association of gamma-glutamyltransferase with severity of disease at diagnosis and prognosis of ovarian cancer.
BACKGROUND
Gamma-glutamyltransferase (GGT) - a membrane-bound enzyme crucially involved in the cell's detoxification pathway and apoptotic balance - is involved in tumour development, progression and chemotherapy resistance. Elevated GGT serum levels are associated with increased cancer risk in women and worse prognosis in gynaecologic cancers. The present study investigated the prognostic role of GGT in ovarian cancer patients.


METHODS
In this multicenter study, pre-therapeutic GGT levels were ascertained in 634 consecutive patients with epithelial ovarian cancer (EOC, n=567) and borderline tumour of the ovary (BTO, n=67). Gamma-glutamyltransferase serum levels were associated with clinicopathological 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(-1)) than in patients with BTO (20.01 (12.78) U l(-1), 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 tumour tissue and observed an association between these two parameters (P=0.03).


CONCLUSIONS
High pre-therapeutic GGT serum levels are associated with advanced tumour stage and serve as an independent prognostic marker for worse overall survival in patients with EOC. Gamma-glutamyltransferase expression in ovarian cancer tissue is reflected in GGT serum levels.
Department of General Gynecology and Gynecologic Oncology, Medical University of Vienna, Vienna, Austria. christoph.grimm@meduniwien.ac.at
C
C
Grimm
G
G
Hofstetter
S
S
Aust
I
I
Mutz-Dehbalaie
M
M
Bruch
G
G
Heinze
J
J
Rahhal-Schupp
A
A
Reinthaller
N
N
Concin
S
S
Polterauer
D000077216:Carcinoma, Ovarian Epithelial; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D009367:Neoplasm Staging; D009375:Neoplasms, Glandular and Epithelial / Q000201:enzymology* / Q000473:pathology; D010051:Ovarian Neoplasms / Q000201:enzymology* / Q000473:pathology; D011379:Prognosis; D012720:Severity of Illness Index; D005723:gamma-Glutamyltransferase / Q000097:blood*
D005723:gamma-Glutamyltransferase