title: IMP3 expression in lesions of the biliary tract: a marker for high-grade dysplasia and an independent prognostic factor in bile duct carcinomas.
abstract: The oncofetal protein IMP3 (insulin-like growth factor II mRNA binding protein 3) is expressed during embryogenesis and carcinogenesis. Various tumor types have been analyzed for IMP3 expression, which was exclusively found in tumor cells and correlated with increased tumor aggressiveness and reduced overall survival. To our knowledge, IMP3 expression has not been investigated in bile duct carcinomas. Using large tissue sections from resection specimens of the extrahepatic biliary tract, we analyzed IMP3 in normal bile ducts (n = 36), bile ducts with acute inflammation and reactive epithelial changes (n = 26), low-grade dysplasia (n = 9), and high-grade dysplasia (n = 11). Furthermore, IMP3 expression was assessed in bile duct carcinoma (n = 115) using clinically well-characterized tissue microarrays. The findings were correlated with clinical-pathologic parameters including survival. High-grade dysplasia was strongly positive for IMP3 in all cases studied compared with no or weak expression in normal, inflamed, and low-grade dysplastic bile ducts. Of the bile duct carcinomas 58.3% (67/115) were strongly positive for IMP3, which was associated with a higher proliferation rate (P = .004) and p53 positivity (P = .022). Patients with strong IMP3 expression had significantly reduced overall survival (P = .037) similarly to the subgroup of pT3 carcinomas (P = .007). In multivariate analysis, IMP3 expression was an independent prognostic factor for overall survival (P = .040, RR = 1.809). This comprehensive study shows that IMP3 is an independent prognostic biomarker in bile duct carcinoma. In addition, it may be a marker for high-grade dysplasia in the extrahepatic biliary tract.
authors.affiliation: Department of Pathology, University Hosptial Zurich, Zurich, Switzerland.
authors.forename: Marc-Oliver
authors.initials: MO
authors.lastname: Riener
authors.forename: Florian R
authors.initials: FR
authors.lastname: Fritzsche
authors.forename: Pierre-Alain
authors.initials: PA
authors.lastname: Clavien
authors.forename: Bernhard C
authors.initials: BC
authors.lastname: Pestalozzi
authors.forename: Nicole
authors.initials: N
authors.lastname: Probst-Hensch
authors.forename: Wolfram
authors.initials: W
authors.lastname: Jochum
authors.forename: Glen
authors.initials: G
authors.lastname: Kristiansen
mesh_terms: D001650:Bile Duct Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D014408:Biomarkers, Tumor / Q000032:analysis*; D002277:Carcinoma / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D009367:Neoplasm Staging; D011379:Prognosis; D016601:RNA-Binding Proteins / Q000096:biosynthesis*; D046888:Tissue Array Analysis
chemical_list: D014408:Biomarkers, Tumor; C498780:IGF2BP3 protein, human; D009363:Neoplasm Proteins; D016601:RNA-Binding Proteins