Elsevier

Obstetrics & Gynecology

Volume 100, Issue 2, August 2002, Pages 281-287
Obstetrics & Gynecology

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

https://doi.org/10.1016/S0029-7844(02)02040-9Get rights and content

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.

Section snippets

Materials and methods

Between 1988 and 1997, 662 Japanese women with epithelial ovarian cancer underwent primary treatment at the Tottori University Hospital, the Kurume University Hospital, the National Defense Medical College Hospital, and the Jichi Medical School Hospital. Approval for this study was obtained from the Institutional Review Board of Tottori University, School of Medicine. Of 662 patients, 101 patients with dominant or pure clear cell carcinoma and 235 with pure serous adenocarcinoma were observed.

Results

Characteristics of the patients are shown in Table 1. The mean age of patients with clear cell carcinoma was significantly younger than that of those with serous adenocarcinoma (P < .05). Distribution of FIGO stages did not differ between clear cell carcinoma and serous adenocarcinoma (Table 1). The estimated 5-year survival rate for patients with clear cell carcinoma was significantly poorer than that for those with serous adenocarcinoma (20.0% versus 31.9%, P < .001) (Figure 1). The median

Discussion

In the present study, the survival rate for patients with clear cell carcinoma was significantly lower than for patients with serous adenocarcinoma, although age of patients with clear cell carcinoma was younger. Furthermore, patients with clear cell carcinoma had a very low response to chemotherapy and a high incidence of progressive disease. In contrast, patients with serous adenocarcinoma had a high response rate. Goff et al5 also reported a higher incidence of progressive disease with

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