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The Relationship of Insulin-Like Growth Factor-II, Insulin-Like Growth Factor Binding Protein-3, and Estrogen Receptor- Expression to Disease Progression in Epithelial Ovarian Cancer

Authors' Affiliations: ¹ Department of Epidemiology and Public Health, Yale Cancer Center, Yale University School of Medicine, New Haven, Connecticut and ² Department of Obstetrics and Gynecology, Gynecologic Oncology and Breast Cancer Unit, University of Turin, Turin, Italy

Requests for reprints: Herbert Yu, Department of Epidemiology and Public Health, Yale Cancer Center, Yale University School of Medicine, 60 College Street, New Haven, CT 06520-8034. Phone: 203-785-5688; Fax: 203-785-2850; E-mail: herbert.yu{at}yale.edu.

Purpose: The insulin-like growth factor (IGF) system plays important roles in cancer; blocking IGF signaling has been shown to have therapeutic effects on tumor growth. Many studies have focused on the effect of IGF-I, but few have addressed IGF-II. To assess the role of IGF-II in cancer, we analyzed IGF-II expression in ovarian cancer and examined its association with disease characteristics and prognosis.

Experimental Design: Included in the study were 215 patients with primary epithelial ovarian cancer. Fresh tumor specimens were collected during surgery, and the patients were followed for a median of 31 months. Total RNA was extracted from the tumor and analyzed for IGF-II, IGF binding protein 3 (IGFBP-3), and estrogen receptor- expressions using quantitative reverse transcription PCR. Survival analysis was done to examine the associations of IGF-II with disease progression.

Results: IGF-II expression was found to be higher in tumors with poor prognosis; this included tumors with advanced stage, poor differentiation, serous histology, and large residual lesions. Patients with high IGF-II had elevated risk for disease progression and death, although the significance became less evident when the analysis was adjusted for clinical and pathologic variables. IGFBP-3 expression was higher in less aggressive tumors, but was not associated with disease progression. The expression of estrogen receptor- had no effect on survival.

Conclusion: This study found evidence that IGF-II expression is associated with disease progression, suggesting that IGF-II and IGF signaling are potential targets for ovarian cancer treatment. The study also indicates that IGF-II and IGFBP-3 have limited value in prognosis because of their strong associations with disease stage and tumor grade.

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