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Intraductal papillary neoplasms of the bile duct: stepwise progression to carcinoma involves common molecular pathways.

  • Schlitter AM Institute of Pathology, Technische Universität München, München, Germany.
  • Born D Institute of Pathology, University of Bern, Bern, Switzerland.
  • Bettstetter M Molecular Pathology South Bavaria, Trogerstr. 18, München, Germany.
  • Specht K Institute of Pathology, Technische Universität München, München, Germany.
  • Kim-Fuchs C Department of Visceral Surgery and Medicine, Inselspital, Bern, Switzerland.
  • Riener MO Institute of Pathology, University Hospital Erlangen, Erlangen, Germany.
  • Jeliazkova P Department of Internal Medicine, Klinikum rechts der Isar, Technische Universität München, München, Germany.
  • Sipos B Institute of Pathology, University of Tübingen, Tübingen, Germany.
  • Siveke JT Department of Internal Medicine, Klinikum rechts der Isar, Technische Universität München, München, Germany.
  • Terris B Division of Pathological Anatomy, Hôpital Cochin, Université Paris Descartes, Paris, France.
  • Zen Y Institute of Liver Studies, King's College Hospital, London, UK.
  • Schuster T Department of Medical Statistics and Epidemiology, Technische Universität München, München, Germany.
  • Höfler H Institute of Pathology, Technische Universität München, München, Germany.
  • Perren A Institute of Pathology, University of Bern, Bern, Switzerland.
  • Klöppel G Institute of Pathology, Technische Universität München, München, Germany.
  • Esposito I Institute of Pathology, Technische Universität München, München, Germany.
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  • 2013-07-06
Published in:
  • Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc. - 2014
Adult
Aged
Aged, 80 and over
Bile Duct Neoplasms
Bile Ducts, Intrahepatic
Biomarkers, Tumor
Biopsy
Carcinoma in Situ
Carcinoma, Intraductal, Noninfiltrating
Cholangiocarcinoma
Cyclin-Dependent Kinase Inhibitor p16
DNA Mutational Analysis
Disease Progression
Europe
Female
Humans
Immunohistochemistry
Kaplan-Meier Estimate
Male
Middle Aged
Mutation
Neoplasm Grading
Neoplasm Invasiveness
Papilloma
Prognosis
Proportional Hazards Models
Proto-Oncogene Proteins
Proto-Oncogene Proteins p21(ras)
Signal Transduction
Time Factors
Tumor Suppressor Protein p53
ras Proteins
English Intraductal papillary neoplasms of the bile duct are still poorly characterized regarding (1) their molecular alterations during the development to invasive carcinomas, (2) their subtype stratification and (3) their biological behavior. We performed a multicenter study that analyzed these issues in a large European cohort. Intraductal papillary neoplasms of the bile duct from 45 patients were graded and subtyped using mucin markers and CDX2. In addition, tumors were analyzed for common oncogenic pathways, and the findings were correlated with subtype and grade. Data were compared with those from 22 extra- and intrahepatic cholangiocarcinomas. Intraductal papillary neoplasms showed a development from preinvasive low- to high-grade intraepithelial neoplasia to invasive carcinoma. Molecular and immunohistochemical analysis revealed mutated KRAS, overexpression of TP53 and loss of p16 in low-grade intraepithelial neoplasia, whereas loss of SMAD4 was found in late phases of tumor development. Alterations of HER2, EGFR, β-catenin and GNAS were rare events. Among the subtypes, pancreato-biliary (36%) and intestinal (29%) were the most common, followed by gastric (18%) and oncocytic (13%) subtypes. Patients with intraductal papillary neoplasm of the bile duct showed a slightly better overall survival than patients with cholangiocarcinoma (hazard ratio (cholangiocarcinoma versus intraductal papillary neoplasm of the bile duct): 1.40; 95% confidence interval: 0.46-4.30; P=0.552). The development of biliary intraductal papillary neoplasms of the bile duct follows an adenoma-carcinoma sequence that correlates with the stepwise activation of common oncogenic pathways. Further large trials are needed to investigate and verify the finding of a better prognosis of intraductal papillary neoplasms compared with conventional cholangiocarcinoma.
Language
  • English
Open access status
bronze
Identifiers
Persistent URL
https://sonar.ch/global/documents/172597
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