Significance of multi-drug-resistant proteins in predicting chemotherapy response and prognosis in epithelial ovarian cancer.
OBJECTIVE
To clarify the expression of multi-drug-resistant (MDR) markers, GST-pi, c-Jun, P-glycoprotein (Pgp), and MDR-associated protein (MRP) in epithelial ovarian cancer, and to determine whether their expression is predictive of chemotherapy response and patient prognosis.


METHODS
Specimens of 58 epithelial ovarian cancer cases obtained at initial surgery were studied immunohistochemically using antibodies.


RESULTS
Overall positive rates in the 58 specimens were 58.6% for GST-pi, 44.8% for c-Jun, 27.6% for Pgp, and 22.4% for MRP. The 5-year disease-free survival rate was 26.0% for patients with MRP-positive tumors and 75.2% for those with MRP-negative tumors. The prognosis for those with MRP-positive tumors was significantly poorer (p < 0.05). Patients with GST-pi-positive tumors had a significantly worse prognosis than those with GST-pi-negative tumors (51.9% vs 79.2%, p < 0.05). Multivariate analysis showed that residual tumors 2 cm or larger and MRP expression were independent prognostic factors for chemotherapy resistance. The relative risk of chemotherapy resistance in a patient with a residual tumor 2 cm or larger, positive MRP, and positive GST-pi was 10.6 times greater than the risk in a patient without these factors.


CONCLUSIONS
MRP and GST-pi expression might be potential predictors of the response to standard chemotherapy in epithelial ovarian cancer. Their expression also might contribute to individualizing clinical trials of postoperative chemotherapy.
Yokoyama
Y
Y
Department of Obstetrics and Gynecology, Hirosaki University School of Medicine, Japan.
Sato
S
S
Fukushi
Y
Y
Sakamoto
T
T
Futagami
M
M
Saito
Y
Y
D000970:Antineoplastic Agents / Q000627:therapeutic use; D015415:Biomarkers; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D019450:Genes, MDR / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D007564:Japan / Q000453:epidemiology; D009363:Neoplasm Proteins / Q000032:analysis*; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000401:mortality*; D011237:Predictive Value of Tests; D012189:Retrospective Studies
D000970:Antineoplastic Agents; D015415:Biomarkers; D009363:Neoplasm Proteins