KRAS mutation testing in human cancers: The pathologist's role in the era of personalized medicine

Adv Anat Pathol. 2010 Jan;17(1):23-32. doi: 10.1097/PAP.0b013e3181c6962f.

Abstract

A number of studies have shown that although antiepidermal growth factor receptor (EGFR) monoclonal antibodies are effective treatments for metastatic colorectal cancer (mCRC), only patients with wild-type KRAS tumors derive clinical benefit from these therapies. The anti-EGFR monoclonal antibodies panitumumab and cetuximab are approved in the United States for treatment of mCRC refractory to chemotherapy but are not recommended for use in patients with mutations in KRAS codons 12 or 13. Similarly, panitumumab is approved for the treatment of mCRC only in patients with wild-type KRAS in Europe and Canada. It is clear that KRAS mutational analysis will become an important aspect of disease management in patients with mCRC. Consequently, it will be important for pathologists and oncologists to develop and agree on standardized KRAS testing and reporting procedures to ensure optimum patient care. Pathologists will be central to this process because of their crucial role in selecting appropriate tumor specimens for testing, choosing the molecular diagnostic laboratory to be used, assisting in the selection of a suitable KRAS test, and interpreting the results of KRAS mutational analysis. Guidelines for KRAS testing that address these and other important points of consideration have recently been proposed in the United States and the European Union.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antibodies, Monoclonal / therapeutic use
  • Antibodies, Monoclonal, Humanized
  • Cetuximab
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / pathology
  • DNA Mutational Analysis / standards
  • ErbB Receptors / genetics
  • ErbB Receptors / therapeutic use*
  • Genes, ras / genetics*
  • Humans
  • Neoplasm Metastasis / genetics*
  • Neoplasms / genetics*
  • Panitumumab
  • Pathology, Molecular
  • Polymerase Chain Reaction
  • Precision Medicine
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins / physiology
  • Proto-Oncogene Proteins p21(ras)
  • Sensitivity and Specificity
  • Signal Transduction
  • ras Proteins / genetics*
  • ras Proteins / physiology

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • KRAS protein, human
  • Proto-Oncogene Proteins
  • Panitumumab
  • ErbB Receptors
  • Proto-Oncogene Proteins p21(ras)
  • ras Proteins
  • Cetuximab