Diagnostic and prognostic value of incidence of K-ras codon 12 mutations in resected distal bile duct carcinoma.
OBJECTIVE
The K-ras gene is one of the most extensively investigated oncogenes in a wide variety of human tumors, but has rarely been studied in distal bile duct carcinoma (DBDC). We sought to investigate the diagnostic and prognostic value of K-ras codon 12 mutations in this type of tumor.


METHODS
Forty-seven patients who had undergone resection for DBDC were analyzed to reveal the incidence of K-ras codon 12 mutations, the locus most frequently involved. A rapid and simple two-step, semi-nested polymerase chain reaction (PCR) technique was used to detect mutations in paraffin-embedded tumor samples.


RESULTS
The PCR mismatch amplification technique demonstrated that 35 (75%) of the 47 tumors harbored a point mutation in codon 12 of the K-ras oncogene. Patients with mutated tumors had no statistically different survival time compared to those patients without a mutation in the tumor. In contrast, negative microscopic margins proved to be a significant prognosticator.


CONCLUSIONS
K-ras codon 12 mutations are common in DBDC and may be useful in the diagnosis and early detection of these tumors. However, no prognostic value of these mutations could be identified in this analysis. The results of this study also suggest that negative surgical margins remain the mainstay of prognostication in resectable DBDC. However, due to the small number of patients included in this study, the results obtained should be interpreted with care.
Department of Surgery, Academic Medical Center, University of Amsterdam, The Netherlands.
A M
AM
Rijken
T M
TM
van Gulik
M M
MM
Polak
P D
PD
Sturm
D J
DJ
Gouma
G J
GJ
Offerhaus
D000230:Adenocarcinoma / Q000175:diagnosis* / Q000235:genetics* / Q000401:mortality / Q000601:surgery; D000328:Adult; D000368:Aged; D001650:Bile Duct Neoplasms / Q000175:diagnosis* / Q000235:genetics* / Q000401:mortality / Q000601:surgery; D017734:Bile Ducts, Extrahepatic; D003062:Codon / Q000235:genetics*; D005260:Female; D011905:Genes, ras / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D011379:Prognosis; D015996:Survival Rate
D003062:Codon