Science et thérapie du cancer

Kras, Braf, PIK3CA and EGFR Gene Mutations are Associated with Lymph Node Metastasis and Right Sided Colon Carcinoma

Abstract

Abrar Ahmad, Abdul Mannan and Victoria Hahn-Strömberg

Mitogen activated proteinase kinase (MAPK) is a key regulator of cellular growth and survival. Mutations in the MAPK pathway genes such as EGFR, KRAS, BRAF and PIK3CA lead to cellular disequilibrium that result into overgrowth and different type of carcinoma including colorectal carcinoma (CRC). Different techniques have been used to determine mutations in the above mentioned genes, and frequency of mutations can vary in different population. The aim of our study was to evaluate the frequency of mutations in the hotspot regions of EGFR, KRAS, BRAF and PIK3CA genes in Swedish colon carcinoma patients by pyrosequencing, and to correlate with different clinicopathological parameters and patient survival. We screened 124 colon cancer patients by using pyrosequencing. We detected Kras, Braf and PIK3CA mutations in 24%, 18.5% and 5.6% of the patients respectively while no mutation was observed for EGFR in our cohort. Kras mutations significantly correlated with lymph node metastasis and advanced UICC stages and poor patient survival (HR; 2.26, 95% CI; 1.273-4.13, log rank P, 0.006). Non-significant correlations were observed between Braf and all parameters including patient survival except with right sided colon cancer. PIK3CA mutations were associated with lymph node metastasis, distant metastasis and higher UICC stages. Combined mutations in Kras, Braf and PIK3CA were significantly associated with lymph node metastasis and colon cancer located on the right flexure. PIK3CA and Kras co-mutations were observed in 4 patients and were significantly associated with lymph node metastasis, distant metastasis and advanced UICC stages.