IGF2BP3 (IMP3) expression is a marker of unfavorable prognosis in ovarian carcinoma of clear cell subtype.
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.
Köbel
Martin
M
Department of Pathology, Genetic Pathology Evaluation Centre of the Prostate Research Centre, Vancouver General Hospital and British Columbia Cancer Agency, Vancouver, BC, Canada.
Xu
Haodong
H
Bourne
Patricia A
PA
Spaulding
Betsy O
BO
Shih
Ie-Ming
IeM
Mao
Tsui-Lien
TL
Soslow
Robert A
RA
Ewanowich
Carol A
CA
Kalloger
Steve E
SE
Mehl
Erika
E
Lee
Cheng-Han
CH
Huntsman
David
D
Gilks
C Blake
CB
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
D014408:Biomarkers, Tumor; C498780:IGF2BP3 protein, human; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins