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
StatePublished - 2000

Fingerprint

Biliary Tract Neoplasms
Sclerosing Cholangitis
ras Genes
Mutation
Neoplasms
Survival
Cholangiocarcinoma
DNA Sequence Analysis
Ligation
Proteins

Keywords

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

ASJC Scopus subject areas

  • Surgery

Cite this

p53 overexpression and K-ras gene mutations in primary sclerosing cholangitis-associated biliary tract cancer. / Ahrendt, Steven A.; Rashid, Asif; Chow, John T.; Eisenberger, Claus F.; Pitt, Henry A.; Sidransky, David.

In: Journal of Hepato-Biliary-Pancreatic Surgery, Vol. 7, No. 4, 2000, p. 426-431.

Research output: Contribution to journalArticle

Ahrendt, Steven A. ; Rashid, Asif ; Chow, John T. ; Eisenberger, Claus F. ; Pitt, Henry A. ; Sidransky, David. / p53 overexpression and K-ras gene mutations in primary sclerosing cholangitis-associated biliary tract cancer. In: Journal of Hepato-Biliary-Pancreatic Surgery. 2000 ; Vol. 7, No. 4. pp. 426-431.
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