title: The frequency of KRAS and BRAF mutations in intrahepatic cholangiocarcinomas and their correlation with clinical outcome.
abstract: The incidence of intrahepatic cholangiocarcinoma is increasing worldwide. The prognosis of intrahepatic cholangiocarcinoma is poor, and a better understanding of intrahepatic cholangiocarcinoma tumor biology is needed to more accurately predict clinical outcome and to suggest potential targets for more effective therapies. v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) and BRAF are frequently mutated oncogenes that promote carcinogenesis in a variety of tumor types. In this study, we analyze a large set of intrahepatic cholangiocarcinoma tumors (n = 54) for mutations in these genes and compare the clinical outcomes of wild type versus KRAS and BRAF mutant cases. Of 54 cases, 7.4% were mutant for KRAS, 7.4% were mutant for BRAF, and these were mutually exclusive. These mutant cases were associated with a higher tumor stage at time of resection and a greater likelihood of lymph node involvement. These cases were also associated with a worse long-term overall survival. Therefore, testing for KRAS and BRAF mutations could be a valuable adjunct in improving both prognosis and outcome stratification among patients with intrahepatic cholangiocarcinoma.
authors.affiliation: Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
authors.forename: Scott
authors.initials: S
authors.lastname: Robertson
authors.forename: Omar
authors.initials: O
authors.lastname: Hyder
authors.forename: Rebecca
authors.initials: R
authors.lastname: Dodson
authors.forename: Suresh K
authors.initials: SK
authors.lastname: Nayar
authors.forename: Justin
authors.initials: J
authors.lastname: Poling
authors.forename: Katie
authors.initials: K
authors.lastname: Beierl
authors.forename: James R
authors.initials: JR
authors.lastname: Eshleman
authors.forename: Ming-Tseh
authors.initials: MT
authors.lastname: Lin
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Pawlik
authors.forename: Robert A
authors.initials: RA
authors.lastname: Anders
mesh_terms: D000368:Aged; D018281:Cholangiocarcinoma / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D015996:Survival Rate; D018631:ras Proteins / Q000235:genetics*
chemical_list: C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins
keywords: BRAF mutations; Intrahepatic cholangiocarcinoma; KRAS mutations