Journal of Hepato-Biliary-Pancreatic Surgery

, Volume 7, Issue 4, pp 426–431

p53 overexpression and K-ras gene mutations in primary sclerosing cholangitis-associated biliary tract cancer

  • Steven A. Ahrendt
  • Asif Rashid
  • John T. Chow
  • Claus F. Eisenberger
  • Henry A. Pitt
  • David Sidransky

DOI: 10.1007/s005340070039

Cite this article as:
Ahrendt, S., Rashid, A., Chow, J. et al. J Hep Bil Pancr Surg (2000) 7: 426. doi:10.1007/s005340070039

Abstract

Cholangiocarcinoma occurs frequently in patients with primary sclerosing cholangitis (PSC). We evaluated the incidence and prognostic significance of p53 protein overexpression and K-ras gene mutations in patients with biliary tract cancer and PSC. p53 protein expression was determined in specimens from 12 patients with biliary tract cancer, using the antibody, D07. K-ras mutations were detected using DNA sequencing and a mutation ligation assay. Accumulation of p53 protein was detected in 6 of 12 tumors (50%). K-ras mutations were detected in 4 of 12 tumors (33%). Overall survival in patients with p53-negative tumors was significantly longer (P < 0.05) than that in patients with p53-positive (mutant) tumors. Similarly, overall survival was significantly longer (P < 0.05) in the absence of a K-ras mutation than in patients with a tumor containing a K-ras mutation. Mean interval from the time of diagnosis of PSC until the diagnosis of biliary tract cancer was significantly shorter (P < 0.05) in patients with p53 overexpression than in those patients without p53 overexpression (2 versus 47 months). p53 overexpression and K-ras mutations occur commonly in patients with PSC and biliary tract cancer and are associated with a shortened survival. Patients with longstanding PSC are less likely to have these genetic alterations and may have a better prognosis.

Key words Primary sclerosing cholangitisCholangiocarcinomap53 mutationp53 overexpressionK-ras mutationGallbladder cancer

Copyright information

© Springer-Verlag Tokyo 2000

Authors and Affiliations

  • Steven A. Ahrendt
    • 1
  • Asif Rashid
    • 2
  • John T. Chow
    • 3
  • Claus F. Eisenberger
    • 3
  • Henry A. Pitt
    • 1
  • David Sidransky
    • 3
  1. 1.Department of Surgery, Medical College of Wisconsin, 9200 West Wisconsin Avenue, Milwaukee, WI 53226, USAUS
  2. 2.Department of Pathology, The Johns Hopkins School of Medicine, Baltimore, MD, USAUS
  3. 3.Department of Otolaryngology-Head and Neck Surgery, The Johns Hopkins School of Medicine, Baltimore, MD, USAUS
  4. 4.Oncology Center, The Johns Hopkins School of Medicine, Baltimore, MD, USAUS