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

Future Oncol. 2015;11(4):629-40. doi: 10.2217/fon.14.279.

Abstract

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 × 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.

Keywords: EGFR pathway; colorectal cancer; mutational profiling; prognostic factors.

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols
  • Class I Phosphatidylinositol 3-Kinases
  • Colorectal Neoplasms / drug therapy
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / mortality*
  • Colorectal Neoplasms / pathology
  • Combined Modality Therapy
  • DNA Mutational Analysis
  • Female
  • GTP Phosphohydrolases / genetics*
  • Humans
  • Male
  • Membrane Proteins / genetics*
  • Mutation Rate
  • Mutation*
  • Neoplasm Staging
  • Phosphatidylinositol 3-Kinases / genetics*
  • Prognosis
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins B-raf / genetics*
  • Proto-Oncogene Proteins p21(ras)
  • Retrospective Studies
  • Treatment Outcome
  • ras Proteins / genetics*

Substances

  • KRAS protein, human
  • Membrane Proteins
  • Proto-Oncogene Proteins
  • Phosphatidylinositol 3-Kinases
  • Class I Phosphatidylinositol 3-Kinases
  • PIK3CA protein, human
  • Proto-Oncogene Proteins B-raf
  • GTP Phosphohydrolases
  • NRAS protein, human
  • Proto-Oncogene Proteins p21(ras)
  • ras Proteins