Objective: This study was conducted to assess the predictive value of P-glycoprotein (P-gp) and glutathione S-transferase-pi(GST-pi) as indicators of resistance to chemotherapy in ovarian cancers.
Methods: Expressions of P-gp and GST-pi were immunohistochemically studied in paraffin sections from 30 normal ovaries and 74 resected specimens of primary epithelial ovarian cancer from patients who had not received any chemotherapy before surgery.
Results: There were no detectable P-gp or GST-pi expression in the 30 patients with normal ovaries. In 74 cases of ovarian cancer tissue, P-gp was positive in 14 (18.9%) and GST-pi positive in 55 (74.3%) showing a highly significant correlation (P < 0.01). However, expression of P-gp and GST-pi was not associated with any of the clinicopathological parameters, such as clinical stage, histologic or tumor grade (P > 0.05). The evaluation of chemotherapy for postoperative residual ovarian cancer patients showed that all the six lesions showing P-gp positive were drug-resistant whereas only nine of the twenty-one tumors showing negative results were drug-resistant. Of 27 clinically measurable resected lesions, this difference in the response rates of the two groups was significant (P < 0.05). The predictive value of positive P-gp stain for drug resistance was 100% (6/6), and that of negative stain for objective responders was 57.1%(12/21). The response rate to chemotherapy of the GST-pi positive group (13.3%-2/15) was significantly lower than that of the SGT-pi negative group (83.3%-10/12, P < 0.01). The predictive value of positive GST-pi stain for drug resistance was 86.7%(13/15) and that of negative stain for objective responders was 83.3%(10/12). The survival rates of P-gp negative and GST-pi negative tumor patients were significantly higher than those of P-gp positive and GST-pi positive tumor patients (P < 0.01, P < 0.05, respectively).
Conclusion: These data suggest that P-gp and GST-pi expression in tumor cells are related to drug resistance in epithelial ovarian cancer. They are useful indicators of resistance to chemotherapy.