GSTP1-1 in ovarian cyst fluid and disease outcome of patients with ovarian cancer.
Detoxification enzymes, especially glutathione S-transferase P1-1 (GSTP1-1), have been implicated in resistance to platinum-based chemotherapy. We studied GSTP1-1 levels in ovarian cyst fluid (oCF), obtained during surgery before chemotherapy, of patients with epithelial ovarian cancer and clinical outcomes were correlated. GSTP1-1 was determined by ELISA in oCF of 56 patients with epithelial ovarian cancer and 109 noncancer controls (21 borderline and 88 benign ovarian tumors). Differences in median GSTP1-1 between clinicopathologic subgroups were studied using Mann-Whitney U and Kruskal Wallis tests. Differences in disease-free (DFS) and overall survival (OS) between groups were analyzed by applying Kaplan-Meyer estimates and log-rank tests. Univariate and multivariate analysis were done using Cox proportional hazard model. Significantly higher levels of GSTP1-1 were found in the oCF of malignant (median, 383; range, 10-32,695 ng/mL) compared with benign (median, 20; range, 0-1,128 ng/mL) ovarian tumors (P < 0.01). Significantly higher GSTP1-1 levels were found in patients with advanced International Federation of Gynaecologists and Obstetricians stage (P = 0.01), high-grade tumors (P = 0.44), and/or high levels of preoperative CA 125 (P = 0.01). Of patients who received chemotherapy (stage, >or=Ic; n = 30), high GSTP1-1 levels were significantly associated with a poor DFS and OS (log-rank P = 0.047 and P = 0.033, respectively). International Federation of Gynaecologists and Obstetricians stage was the only independent predictor for DFS. GSTP1-1 was the only independent predictor for OS.
Kolwijck
Eva
E
Department of Obstetrics and Gynecology, Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands. E.Kolwijck@obgyn.umcn.nl
Zusterzeel
Petra L M
PL
Roelofs
Hennie M J
HM
Hendriks
Jan C
JC
Peters
Wilbert H M
WH
Massuger
Leon F A G
LF
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000032:analysis*; D020420:Cyst Fluid / Q000737:chemistry / Q000201:enzymology; D018572:Disease-Free Survival; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D051549:Glutathione S-Transferase pi / Q000032:analysis / Q000378:metabolism*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D009367:Neoplasm Staging; D009375:Neoplasms, Glandular and Epithelial / Q000201:enzymology* / Q000401:mortality / Q000473:pathology; D010048:Ovarian Cysts / Q000737:chemistry / Q000201:enzymology* / Q000473:pathology; D010051:Ovarian Neoplasms / Q000201:enzymology* / Q000401:mortality / Q000473:pathology; D011379:Prognosis; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D051549:Glutathione S-Transferase pi