Chemesensitivity of clear cell carcinoma of the ovary

The insensitivity of clear cell carcinoma (CCC) of the ovary to platinum-based chemotherapy is associated with its poor prognosis. However, the mechanism underlying CCC's resistance to platinum has not been understood. We discussed the mechanism of cisplatin (CDDP)-resistance in CCC cells. First, clinicopathological features of CCC were reviewed. Patients with CCC were significantly more likely to have staged I disease than were patients with serous adenocarcinoma (SAC). The survival rate for stage III CCC patients were significantly lower compared with SAC patients. The response rate to platinum-based chemotherapy in patients with CCC was significantly lower than in patients with SAC. Those findings indicates that CCC are an intriguing histologic type of epithelial ovarian cancers that demonstrate a distinctly different clinical behavior than that of SAC. In vitro study showed that the IC 50 to anticancer agents ranged widely. The assay AUC indicated that CCC were resistant to mitomycin-C (MMC) and etoposide (VP-16). PTX and CPT-11 might be effective agents to CCC. Next, we estimate whether and how the biological behavior of CCC contributes the chemoresistance mechanism. In vitro study revealed a significant reverse correlation between the S-phase fraction and the response to CDDP, suggesting that low cell proliferation may cause the insensitivity of CCC to CDDP. Therefore, 41 patients with CCC and 90 patients with SAC, who had measurable disease after initial surgery, were examined. The expression of P-gp and MRP 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 SAC. The LI for responders was significantly higher than that for nonresponders in both tumor types. When cut-off 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% vs. 9.2%). Multivariable analysis revealed that LI and residual tumor size were the independent prognostic factors. It is concluded that lower proliferation of tumor may be a behavior of clear cell carcinoma of the ovary that contributes to its resistance to chemotherapy.