You are here

Article Text

Article menu
Download PDFPDF
Biliary disease
Frequency of p16INK4A alterations and k-ras mutations in intrahepatic cholangiocarcinoma of the liver
  1. A Tannapfela,
  2. M Benickea,
  3. A Katalinicb,
  4. D Uhlmannc,
  5. F Köckerlingd,
  6. J Haussc,
  7. C Wittekinda
  1. aInstitute of Pathology, University of Leipzig, Liebigstr 26, 04103 Leipzig, Germany, bInstitute of Cancer Epidemiology, University of Lübeck, St Jürgen-Ring 66, 23564 Lübeck, Germany, cDepartment of Surgery II, University of Leipzig, Liebigstr 20a, 04103 Leipzig, Germany, dDepartment of Surgery, Surgical Clinic Hannover, Roesebeckstr 15, 30449 Hannover, Germany
  1. Dr A Tannapfel. tana{at}medizin.uni-leipzig.de

Abstract

BACKGROUND Inactivation of the tumour suppressor gene p16 (CDKN2/MTS-1/INK4A) and K-ras mutations are among the most frequent genetic alterations in human malignancies.

AIMS To investigate the tumour suppressor gene p16 and its possible association with K-ras mutations in intrahepatic cholangiocarcinomas of the liver.

METHODS The status of p16 was evaluated in 41 cholangiocarcinomas by methylation specific polymerase chain reaction, microsatellite analysis, DNA sequencing, and immunohistochemical staining. K-rasmutations were determined by direct DNA sequencing analyses after microdissection. The results obtained were correlated with histopathological variables and patient survival.

RESULTS Hypermethylation of the 5′ CpG island of the p16 gene was found in 34 of 41 (83%) carcinomas. Homozygous deletion at the p16 region was present in two (5%), and loss of heterozygosity (LOH) in eight cases (20%). We failed to detect p16 gene missense mutations. K-rasmutations were found in 22 of 41 (54%) cholangiocarcinomas and in two cases of tumour surrounding non-neoplastic liver tissue. All 22 cancers with K-ras mutations also exhibited methylated p16. We failed to observe a correlation between K-ras or p16 status and histopathological factors or prognosis of patients.

CONCLUSION These data suggest that inactivation of the p16 gene is a frequent event in cholangiocarcinoma. The most common somatic alteration is promotor methylation of the p16 gene which is closely associated with K-ras mutations. We failed to establish p16 or K-ras status as independent prognostic factors in these tumours.

  • cholangiocarcinoma
  • p16
  • K-ras
  • histopathology
  • prognosis
  • methylation

  • Abbreviations used in this paper

    CCC
    cholangiocarcinoma
    HCC
    hepatocellular carcinoma
    PCR
    polymerase chain reaction
    MSP
    methylation specific PCR
    LOH
    loss of heterozygosity
    SSCP
    single strand conformation polymorphism

    • https://doi.org/10.1136/gut.47.5.721

    Statistics from Altmetric.com

      Request Permissions

      If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

    • Abbreviations used in this paper

      CCC
      cholangiocarcinoma
      HCC
      hepatocellular carcinoma
      PCR
      polymerase chain reaction
      MSP
      methylation specific PCR
      LOH
      loss of heterozygosity
      SSCP
      single strand conformation polymorphism
      • View Full Text