title: IGF2BP3 (IMP3) expression is a marker of unfavorable prognosis in ovarian carcinoma of clear cell subtype.
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.
authors.affiliation: Department of Pathology, Genetic Pathology Evaluation Centre of the Prostate Research Centre, Vancouver General Hospital and British Columbia Cancer Agency, Vancouver, BC, Canada.
authors.forename: Martin
authors.initials: M
authors.lastname: Köbel
authors.forename: Haodong
authors.initials: H
authors.lastname: Xu
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Bourne
authors.forename: Betsy O
authors.initials: BO
authors.lastname: Spaulding
authors.forename: Ie-Ming
authors.initials: IeM
authors.lastname: Shih
authors.forename: Tsui-Lien
authors.initials: TL
authors.lastname: Mao
authors.forename: Robert A
authors.initials: RA
authors.lastname: Soslow
authors.forename: Carol A
authors.initials: CA
authors.lastname: Ewanowich
authors.forename: Steve E
authors.initials: SE
authors.lastname: Kalloger
authors.forename: Erika
authors.initials: E
authors.lastname: Mehl
authors.forename: Cheng-Han
authors.initials: CH
authors.lastname: Lee
authors.forename: David
authors.initials: D
authors.lastname: Huntsman
authors.forename: C Blake
authors.initials: CB
authors.lastname: Gilks
mesh_terms: D018262:Adenocarcinoma, Clear Cell / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D014408:Biomarkers, Tumor / Q000032:analysis*; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D011379:Prognosis; D012333:RNA, Messenger / Q000032:analysis; D016601:RNA-Binding Proteins / Q000096:biosynthesis*; D046888:Tissue Array Analysis
chemical_list: D014408:Biomarkers, Tumor; C498780:IGF2BP3 protein, human; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins