title: The status of EGFR-associated genes could predict the outcome and tumor response of chemo-refractory metastatic colorectal patients using cetuximab and chemotherapy.
abstract: OBJECTIVE
  This study was designed to analyze the impacts of status of EGFR-associated genes on the outcome of chemo-refractory mCRC patients using cetuximab.
  
  
  METHODS
  We collected samples from 42 metastatic CRC patients refractory to FOLFOX or FOLFIRI. Mutation profiles of KRAS, BRAF, PTEN, and PI3KCA and the copy numbers of EGFR and PTEN were analyzed. Overall survival and tumor response between various statuses of EGFR-associated genes were compared.
  
  
  RESULTS
  Eleven patients had a partial response to cetuximab with chemotherapy. Sixteen (38.1%) tumors had KRAS mutations. Three (7.1%) had BRAF mutations (V600E) and three (7.1%) had PTEN mutations. No PIK3CA mutation was found. Of 26 wild-KRAS tumors, nine (34.6%) had a partial response to cetuximab: this was higher than that of KRAS-mutated tumors (12.5%). Five patients with BRAF or PTEN mutations did not response to cetuximab. Response rate increased to 45% in patients with all wild-type KRAS, BRAF, and PTEN tumors. Of 16 tumors with high EGFR copy number, eight (50%) responded to cetuximab, a higher response rate than that of tumors with normal EGFR copy number (3/26, P = 0.011). Overall survival of patients was associated with high EGFR copy number and all wild-type tumors.
  
  
  CONCLUSIONS
  EFGR copy number and mutation in EGFR-associated genes could be selective markers in mCRC patients using cetuximab.
authors.affiliation: Division of Colon & Rectal Surgery, Department of Surgery, Taipei Veterans General Hospital, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Jen-Kou
authors.initials: JK
authors.lastname: Lin
authors.forename: An-Jen
authors.initials: AJ
authors.lastname: Lin
authors.forename: Chun-Chi
authors.initials: CC
authors.lastname: Lin
authors.forename: Yuan-Tzu
authors.initials: YT
authors.lastname: Lan
authors.forename: Shung-Haur
authors.initials: SH
authors.lastname: Yang
authors.forename: Anna Fen-Yau
authors.initials: AF
authors.lastname: Li
authors.forename: Shih-Ching
authors.initials: SC
authors.lastname: Chang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D000068818:Cetuximab; D058534:Class I Phosphatidylinositol 3-Kinases; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D000077146:Irinotecan; D008113:Liver Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000556:secondary; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D051059:PTEN Phosphohydrolase / Q000235:genetics; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D012189:Retrospective Studies; D016879:Salvage Therapy; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D000077146:Irinotecan; D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human; C512478:EGFR protein, human; D066246:ErbB Receptors; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human; D000068818:Cetuximab; D002166:Camptothecin