p53 overexpression and K-ras gene mutations in primary sclerosing cholangitis-associated biliary tract cancer.
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.
Ahrendt
S A
SA
Department of Surgery, Medical College of Wisconsin, 9200 West Wisconsin Avenue, Milwaukee, WI 53226, USA.
Rashid
A
A
Chow
J T
JT
Eisenberger
C F
CF
Pitt
H A
HA
Sidransky
D
D
D000328:Adult; D001650:Bile Duct Neoplasms / Q000150:complications / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000601:surgery; D001653:Bile Ducts, Intrahepatic; D018288:Carcinoma, Small Cell / Q000235:genetics / Q000378:metabolism; D018281:Cholangiocarcinoma / Q000150:complications / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000601:surgery; D015209:Cholangitis, Sclerosing / Q000150:complications / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005706:Gallbladder Neoplasms / Q000235:genetics / Q000378:metabolism; D011905:Genes, ras / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D015996:Survival Rate; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D016159:Tumor Suppressor Protein p53