The frequency of KRAS and BRAF mutations in intrahepatic cholangiocarcinomas and their correlation with clinical outcome

Hum Pathol. 2013 Dec;44(12):2768-73. doi: 10.1016/j.humpath.2013.07.026. Epub 2013 Oct 15.

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.

Keywords: BRAF mutations; Intrahepatic cholangiocarcinoma; KRAS mutations.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Cholangiocarcinoma / genetics*
  • Cholangiocarcinoma / mortality
  • Cholangiocarcinoma / pathology
  • Female
  • Humans
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / mortality
  • Liver Neoplasms / pathology
  • Male
  • Middle Aged
  • Mutation*
  • Neoplasm Staging
  • Prognosis
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins B-raf / genetics*
  • Proto-Oncogene Proteins p21(ras)
  • Survival Rate
  • ras Proteins / genetics*

Substances

  • KRAS protein, human
  • Proto-Oncogene Proteins
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf
  • Proto-Oncogene Proteins p21(ras)
  • ras Proteins