Ki-ras mutations as a prognostic factor in extrahepatic bile system cancer. PANK-ras I Project Investigators.
OBJECTIVE
To assess the prevalence and prognostic significance of Ki-ras codon 12 mutations in extrahepatic biliary system cancer (EBSC).


METHODS
Patients diagnosed with EBSC between 1980 and 1990 (N = 111) were selected from two hospitals. DNA was amplified from paraffin-embedded tissues and mutations in codon 12 of Ki-ras were detected using the artificial restriction fragment-length polymorphism (RFLP) technique.


RESULTS
Tissue was available from 68.5% of patients. The prevalence of mutations was 41%. There was no association between mutations and clinical and pathologic characteristics; however, mutations in Ki-ras were associated with survival, with a median survival duration of 7.7 months for patients with wild-type Ki-ras and 1.7 months for patients with mutated tumors (hazards ratio [HR] = 1.67; P = .075). Among patients with stage I to II tumors, the chance of dying of patients with the mutation was 7.8 times higher than that of patients without the mutation (P = .087); the corresponding HR for patients with stage III to IV disease was 2.9 (P = .003). After adjusting for age, tumor site, histology, differentiation, and stage, the HR for Ki-ras mutations was 2.12 (P = .026).


CONCLUSIONS
Ki-ras codon 12 mutations are an independent prognostic indicator in patients with EBSC. Mutation detection may be of help in the management of these patients.
Malats
N
N
Departmetn of Epidemiology, Institut Municipal d'Investigació Mèdica, Barcelona, Spain.
Porta
M
M
Piñol
J L
JL
Corominas
J M
JM
Rifà
J
J
Real
F X
FX
D000230:Adenocarcinoma / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D000368:Aged; D014670:Ampulla of Vater; D001650:Bile Duct Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D017734:Bile Ducts, Extrahepatic; D003062:Codon / Q000235:genetics*; D003138:Common Bile Duct Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D005260:Female; D005706:Gallbladder Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D011905:Genes, ras / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D017354:Point Mutation / Q000235:genetics*; D015995:Prevalence; D011379:Prognosis
D003062:Codon