Multiple drug resistance parameter expression in ovarian cancer.
OBJECTIVE
Drug resistance represents a complex problem for the treatment of ovarian cancer. This study was undertaken to assess several putative resistance parameters (DRP) in parallel in cancer tissue from newly diagnosed patients with ovarian cancer in order to establish possible correlations to known clinical factors and prognosis.


METHODS
Tumor and adjacent tumor free ovarian tissue samples from 39 consecutive, untreated female patients with ovarian cancer were obtained and as potential DRPs, the level of glutathione (GSH), the activities of glutathione S-transferase (GST), glutathione-peroxidase (GPx), O6-alkylguanine-DNA alkyltransferase (Atase), and topoisomerase II (TOPO) were assessed biochemically, and P-glycoprotein (Pgp) was assessed by Western blotting.


RESULTS
Interindividual variations were high and each patient exhibited an individual profile of resistance factor expression. Levels of GSH were increased with stage (linear trend: P < 0.002), and GST, GPx, and Atase showed a similar tendency. With few exceptions no correlation was found between the DRPs and other prognostic characteristics. All tested DRPs except Pgp showed significantly higher levels/activities in tumor tissues than in the surrounding tumor free tissues (P < 0.05). The tested DRPs were found not to influence response to treatment.


CONCLUSIONS
It is concluded that elevated DRPs reflect an intrinsic pattern of components of the detoxifying system in the tumor tissue. This pattern differs between patients and may partly explain the difficulty to assess the clinical importance of individual DRPs in order to translate them into recommendations for specific therapies.
Joncourt
F
F
Institute for Clinical and Experimental Cancer Research, Tiefenaustrasse 120, Bern, Switerland.
Buser
K
K
Altermatt
H
H
Bacchi
M
M
Oberli
A
A
Cerny
T
T
D000328:Adult; D000368:Aged; D004250:DNA Topoisomerases, Type II / Q000032:analysis; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D005260:Female; D005978:Glutathione / Q000032:analysis; D005979:Glutathione Peroxidase / Q000032:analysis; D005982:Glutathione Transferase / Q000032:analysis; D006801:Humans; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis*; D019853:O(6)-Methylguanine-DNA Methyltransferase / Q000032:analysis; D010051:Ovarian Neoplasms / Q000737:chemistry* / Q000188:drug therapy
D009363:Neoplasm Proteins; D005979:Glutathione Peroxidase; D019853:O(6)-Methylguanine-DNA Methyltransferase; D005982:Glutathione Transferase; D004250:DNA Topoisomerases, Type II; D005978:Glutathione