title: Concordance of predictive markers for EGFR inhibitors in primary tumors and metastases in colorectal cancer: a review.
abstract: BACKGROUND
  Currently, only Kirsten rat sarcoma 2 viral oncogene homolog (KRAS) mutational status is used as a decisional marker for epidermal growth factor receptor (EGFR) inhibitor therapy in colorectal cancer (CRC) patients. Concordance of KRAS status between primary tumors and metastases has always been considered to be close to perfect; however, cases of discordance have been reported. The actual rate of concordance of KRAS status remains unclear, as is the same for v-raf murine sarcoma viral oncogene homolog B1 (BRAF), phosphatidylinositol 3-kinase CA subunit (PIK3CA), and loss of phosphatase and tensin homologue deleted on chromosome ten (PTEN). Therefore, it is unknown whether it is necessary to perform mutational analysis on metastases instead of on (or in addition to) primary tumors.
  
  
  METHODS
  A systematic literature search was conducted to collect all studies testing concordance of KRAS in CRC, and also of BRAF, PIK3CA, and loss of PTEN.
  
  
  RESULTS
  Twenty-one studies have reported concordance of KRAS, with an overall concordance rate of 93% (range, 76%-100%). Overall concordance rates of studies testing concordance of BRAF status and loss of PTEN were 98% and 68%, respectively. Three studies reported concordance of PIK3CA status (range, 89%-94%).
  
  
  CONCLUSIONS
  Though discordance of KRAS status does occur, it is uncommon. When considering the downsides of testing metastatic tissue in all patients along with the low incidence of discordance, we conclude that that testing the primary tumor (or whatever tissue available) is sufficient for clinical decision making on EGFR inhibitor therapy.
authors: Department of Clinical Oncology, Leiden University Medical Center, P.O. Box 9600, 2300 RC, Leiden, The Netherlands.
authors: Jara M
authors: JM
authors: Baas
authors: Lisanne L
authors: LL
authors: Krens
authors: Henk-Jan
authors: HJ
authors: Guchelaar
authors: Hans
authors: H
authors: Morreau
authors: Hans
authors: H
authors: Gelderblom
mesh_terms: D000818:Animals; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D009154:Mutation; D009362:Neoplasm Metastasis; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: C117307:KRAS protein, human; D047428:Protein Kinase Inhibitors; D011518:Proto-Oncogene Proteins; D066246:ErbB Receptors; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins