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IMP3 expression in lesions of the biliary tract: a marker for high-grade dysplasia and an independent prognostic factor in bile duct carcinomas


Riener, M O; Fritzsche, F R; Clavien, P A; Pestalozzi, B C; Probst-Hensch, N; Jochum, W; Kristiansen, G (2009). IMP3 expression in lesions of the biliary tract: a marker for high-grade dysplasia and an independent prognostic factor in bile duct carcinomas. Human Pathology, 40(10):1377-1383.

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.

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.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Epidemiology, Biostatistics and Prevention Institute (EBPI)
04 Faculty of Medicine > University Hospital Zurich > Institute of Surgical Pathology
04 Faculty of Medicine > University Hospital Zurich > Clinic for Visceral and Transplantation Surgery
04 Faculty of Medicine > University Hospital Zurich > Division of Surgical Research
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:2009
Deposited On:28 Jan 2010 12:44
Last Modified:05 Apr 2016 13:48
Publisher:Elsevier
ISSN:0046-8177
Publisher DOI:10.1016/j.humpath.2009.01.024
PubMed ID:19467694
Permanent URL: http://doi.org/10.5167/uzh-28502

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