K-ras mutation is strongly associated with perineural invasion and represents an independent prognostic factor of intrahepatic cholangiocarcinoma after hepatectomy.
BACKGROUND
Unsatisfying long-term survival of intrahepatic cholangiocarcinoma (ICC) triggers the clinicians searching for molecular markers, such as K-ras mutation, to tailor management strategy. Additionally, emergence of tyrosine kinase inhibitors (TKIs) brings new hope to palliate advanced ICC; whether the efficacy of TKIs is influenced by k-ras mutation is largely unknown. This study was designed to determine the prevalence of k-ras mutation and its clinical significance in ICC, as well as to pave the reference for future application of TKIs.


METHODS
A total of 86 patients with ICC who underwent hepatectomy were retrospectively recruited. K-ras mutation was determined by using laser capture microdissection and direct sequencing method. Association among clinicopathological variables and K-ras mutation was analyzed. Prognostic factors of ICC after hepatectomy also were determined.


RESULTS
Nineteen (22%) patients exhibited K-ras mutations. Seventeen had their K-ras mutations occurring at codon 12, and the remaining two occurring at codon 13 and codon 61 in one each. Perineural invasion was exclusively the variable associated with K-ras mutation (odds ratio, 6.9) using logistic regression analysis. Multivariate analysis demonstrated that resection margin, T-status, nodal metastasis, and K-ras mutation were independent prognostic factors. The median survival of ICC patients with K-ras mutation was 5.7 months compared with 19.0 months in those without K-ras mutation (P = 0.002).


CONCLUSIONS
The prevalence of K-ras mutations in a considerably large cohort of ICC was 22%. K-ras mutation is strongly associated with perineural invasion phenotypically. K-ras mutation is an independent prognostic factor of ICC after hepatectomy.
Department of Pathology, Chang Gung Memorial Hospital, Chang Gung University, Taoyuan, Taiwan.
Tse-Ching
TC
Chen
Yi-Yin
YY
Jan
Ta-Sen
TS
Yeh
D000368:Aged; D001650:Bile Duct Neoplasms / Q000235:genetics* / Q000473:pathology* / Q000601:surgery; D001653:Bile Ducts, Intrahepatic; D018281:Cholangiocarcinoma / Q000235:genetics* / Q000473:pathology* / Q000601:surgery; D003062:Codon; D005260:Female; D011905:Genes, ras / Q000235:genetics*; D006498:Hepatectomy; D006801:Humans; D053208:Kaplan-Meier Estimate; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation; D009361:Neoplasm Invasiveness; D016017:Odds Ratio; D010525:Peripheral Nerves / Q000473:pathology*; D011379:Prognosis; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D015996:Survival Rate
D003062:Codon