1. ¹Department of Pathology, Genetic Pathology Evaluation Centre of the Prostate Research Centre, Vancouver General Hospital and British Columbia Cancer Agency, Vancouver, BC, Canada
2. ²Institute of Pathology, Charité Hospital, Berlin, Germany
3. ³Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY, USA
4. ⁴Dako North America, Carpinteria, CA, USA
5. ⁵Department of Pathology, Johns Hopkins University, Baltimore, MD, USA
6. ⁶Department of Pathology, National Taiwan University Hospital, Tapei, Taiwan
7. ⁷Surgical Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA
8. ⁸Department of Laboratory Medicine and Pathology, University of Alberta and Royal Alexandra Hospital, Edmonton, AB, Canada

Correspondence: Professor CB Gilks, MD, Department of Pathology, Vancouver General Hospital, Room 1207 1st floor JPPN, 855 West 12th Ave, Vancouver, BC, Canada V5Z 1M9. E-mail: Blake.Gilks@vch.ca

Received 18 July 2008; Revised 3 November 2008; Accepted 4 November 2008; Published online 9 January 2009.

Abstract

Clear cell carcinoma is an uncommon subtype of ovarian carcinoma, accounting for 10% of cases. Clear cell carcinoma typically presents with stage I or II disease, and in this setting prognostic markers could aid in management decisions, in particular the decision to treat with adjuvant chemotherapy. We tested whether expression of insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3, also known as IMP3) can serve as a new biomarker to predict outcome for patients with clear cell carcinoma and other subtypes of ovarian carcinoma. The expression of IGF2BP3 was evaluated by immunohistochemistry in 475 ovarian carcinomas of different subtypes and correlated with disease-specific survival. IGF2BP3 antibody specificity was validated by correlation of IGF2BP3 protein with mRNA expression level in a series of 35 ovarian carcinomas (r=0.849, P<0.0001). IGF2BP3 protein expression was an independent marker of reduced disease-specific survival (risk ratio 2.9, 95% confidence interval 1.4–5.8) in the clear cell subtype (N=128), but not in high-grade serous (N=198) or endometrioid (N=121) carcinomas. The prognostic significance of IGF2BP3 expression for reduced disease-specific survival (risk ratio 2.6, 95% confidence interval 1.3–5.0) was confirmed in an independent series of cases (N=150) from three different centers in North America. We conclude that IGF2BP3 is the first biomarker of prognostic significance in ovarian clear cell carcinoma that has been validated in an independent case series.