Clinicopathological and prognostic significances of EGFR, KRAS, BRAF and PI3KA mutations in biliary tract cancer

BACKGROUND AND AIM:
Biliary tract carcinomas (BTCs) are more common in Korea in western countries. It is more difficult to treat. Epidermal growth factor receptor (EGFR) is a therapeutic target for the cancer. Mutations of the EGFR gene and the activation of its downstream pathways, including KRAS and BRAF, is important for targeted therapy. This study aims to analyze the EGFR, KRAS, BRAF and PI3KCA mutations in BTCs and their association with clinical outcomes.
METHODS:
Paraffin-embedded specimens containing 113 resected BTCs at the Ajou University Hospital between 2009 and 2013 were analyzed. The exons 18-21 of EGFR gene, the codon 12, 13 and 61 of KRAS gene, BRAF V600E, and PI3KCA mutation were analyzed by cobas 4800. We tested the correlation between these mutations and the overall survival, tumor location, stage, and lymphocyte numbers at diagnosis in BTCs.
RESULTS:
There is no mutation of EGFR and BRAF mutation in BTC patients. 23(20.3%) BTC patients had the codon 12, 13 of KRAS mutation, 12(10.6%) patients had the codon 61 of KRAS mutations while 7 (6.1%) patients had PI3KCA mutations. Factors influencing survival on univariate analysis were tumor positive margin, lymphocyte, perineural invasion and bilirubin level. On multivariate analysis, tumor positive margin and perineural invasion were independent prognostic factors. A correlation between KRAS mutations and survival tend to be observed(p=0.051). PI3KCA mutation was not correlated with survival(p=0.956).
CONCLUSIONS:
EGFR and BRAF mutations are not shown in BTCs. KRAS mutation showed 34 patients (31%) and 7 (6.1%) patients had PI3KCA mutations. Tumor positive margin and perineural invasion were independent prognostic markers in BTCs.