Prognostic role of KRAS, NRAS, BRAF and PIK3CA mutations in advanced colorectal cancer

Aim: To explore the prognostic value of extended mutational profiling for metastatic colorectal cancer (mCRC). Materials & methods: We retrospectively reviewed survival results of 194 mCRC patients that were assigned to four molecular subgroups: BRAF mutated; KRAS mutated codons 12-13 only; any of KRAS codons 61-146, PIK3CA or NRAS mutations and all wild-type. Point mutations were investigated by pyrosequencing. Results:BRAF (5.2%) and KRAS 12-13 (31.9%) mutations were associated with poorer survival (HR 2.8 and 1.76, respectively). Presenting with right-sided colon cancer, not resected primary tumor, WBC >10 x 10(9)/l, receiving less chemotherapy or no bevacizumab were all associated with inferior outcome. The all-wild-type subgroup (39.2%) reported the longest survival. Conclusion: Extended mutational profile combined with clinical factors may impact on survival in mCRC.