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

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)426-431
Number of pages6
JournalJournal of Hepato-Biliary-Pancreatic Surgery
Volume7
Issue number4
DOIs
StatePublished - Jan 1 2000

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Keywords

  • Cholangiocarcinoma
  • Gallbladder cancer
  • K-ras mutation
  • Primary sclerosing cholangitis
  • p53 mutation
  • p53 overexpression

ASJC Scopus subject areas

  • Surgery
  • Hepatology

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