title: Epidermal growth factor receptor pathway mutations and colorectal cancer therapy.
abstract: BACKGROUND
  Rational anticancer therapy is beginning to expand the practice of surgical pathology beyond a primarily morphologic and immunophenotypic analysis into the molecular arena. Molecular testing of tumors can have both diagnostic and therapeutic value, which guides treatment decisions. This is true for colorectal cancer in which mutations in signaling mediators predict resistance to anti-epidermal growth factor receptor (anti-EGFR) therapy.
  
  
  OBJECTIVE
  To review the clinically relevant mutations that currently guide treatment decisions in metastatic colorectal cancer, summarize additional mutations that are expected to improve the prognostic sensitivity of molecular testing, and provide practical suggestions for submitting specimens for molecular analysis.
  
  
  METHODS
  Peer-reviewed literature reporting pertinent clinical trial data, mutation analysis, and molecular mechanisms of drug resistance, as well as comprehensive review articles germane to the topic and published testing recommendations from the College of American Pathologists.
  
  
  CONCLUSIONS
  Molecular analysis of colorectal cancer is now mandated before initiation of anti-EGFR therapy and directly impacts treatment options and outcomes. Familiarity with the mutations that determine utility and efficacy of therapy, as well as the importance of careful sample selection, will facilitate appropriate testing and optimize patient care.
authors.affiliation: Department of Pathology, University of Utah Health Sciences Center, Salt Lake City, UT 84108, USA. wade.samowitz@aruplab.com
authors.forename: Allie H
authors.initials: AH
authors.lastname: Grossmann
authors.forename: Wade S
authors.initials: WS
authors.lastname: Samowitz
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000628:therapy; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D009154:Mutation; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D015398:Signal Transduction; D018631:ras Proteins / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D066246:ErbB Receptors; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins