Low proliferation activity may be associated with chemoresistance in clear cell carcinoma of the ovary

Abstract

Objective: To estimate whether and how the biologic behavior of clear cell carcinoma contributes to the chemoresistance mechanism.

Methods: Forty-one patients with clear cell carcinoma and 90 patients with serous adenocarcinoma, who had measurable disease after initial surgery, were examined. All patients underwent cytoreductive surgery followed by platinum-based chemotherapy. P-glycoprotein, multidrug resistance-associated protein, and Ki-67 expression were determined by immunohistochemical staining.

Results: The 5-year survival rate for patients with clear cell carcinoma was significantly poorer, compared with serous adenocarcinoma (20.0% versus 31.9%). Response rate to chemotherapy was 14.6% for clear cell carcinoma and 72.2% for serous adenocarcinoma. The expression of P-glycoprotein and multidrug resistance-associated protein did not differ between responders and nonresponders in both tumor types. The Ki-67 labeling index (LI) in clear cell carcinoma was significantly lower than serous adenocarcinoma (18.4% versus 38.8%). The LI for responders was significantly higher than that for nonresponders in both tumor types. In clear cell carcinoma, the mean value of LI was 15.3% for nonresponders, but that for responders was 30.2%, which was similar to that for serous adenocarcinoma. When the cutoff value of LI was set at 18.4% (mean value), the 5-year survival rate for high LI (over 18.4%) patients was significantly greater than that for low LI patients (46.3% versus 9.2%). Multivariable analysis revealed that LI and residual tumor size were the independent prognostic factors.

Conclusion: Lower proliferation of tumor may be a behavior of clear cell carcinoma of the ovary that contributes to its resistance to chemotherapy.