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Methylation of the insulin-like growth factor binding protein-3 gene and prognosis of epithelial ovarian cancer
  1. A. Wiley*,
  2. D. Katsaros,
  3. S. Fracchioli and
  4. H. Yu*
  1. *Department of Epidemiology and Public Health, Yale Cancer Center, Yale University School of Medicine, New Haven, Connecticut
  2. Department of Obstetrics and Gynecology, Gynecologic Oncology and Breast Cancer Unit, University of Turin, Turin, Italy
  1. Address correspondence and reprint requests to: Herbert Yu, MD, PhD, Department of Epidemiology and Public Health, Yale Cancer Center, Yale University School of Medicine, P.O. Box 208034, New Haven, CT 06520-8034, USA. Email: herbert.yu{at}


Insulin-like growth factor binding protein-3 (IGFBP-3) is a member of the IGFBP family, which regulates the mitogenic and antiapoptotic effects of insulin-like growth factors. Hypermethylation of the IGFBP-3 promoter has been found to suppress its expression. To evaluate the role of IGFBP-3 in ovarian cancer progression, we examined the survival of 235 consecutively selected epithelial ovarian cancer patients in association with IGFBP-3 promoter methylation and IGFBP-3 expression in tumor tissue. IGFBP-3 promoter methylation was analyzed using methylation-specific polymerase chain reaction. Cytosol protein was extracted and measured using a bicinchoninic acid assay; IGFBP-3 was measured by enzyme linked immunosorbent assay. Promoter methylation of the IGFBP-3 gene was detected in 44% (104/235) of patients. IGFBP-3 promoter methylation was associated with disease progression and death after adjusting for clinical and pathologic variables. The association was more evident in patients with early-stage disease: RR = 2.87 (95% CI: 0.78–10.63) for disease progression and RR = 3.94 (95% CI: 0.91–15.78) for death. Tissue levels of IGFBP-3 did not differ by methylation status but were inversely associated with disease stage and residual tumor size. These results suggest that IGFBP-3 promoter methylation may be a useful prognostic marker for disease progression and death in early-stage ovarian cancer.

  • DNA methylation
  • IGFBP-3
  • ovarian cancer
  • prognosis

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