title: Clinical Significance of C-MET Overexpression and Epidermal Growth Factor Receptor Mutation in Platinum-Based Adjuvant Chemotherapy Outcome in Surgically Resected Lung Adenocarcinoma.
abstract: OBJECTIVE
  We retrospectively assessed the role of C-MET expression and epidermal growth factor receptor (EGFR) mutation on survival following platinum-based adjuvant chemotherapy. The impact of C-MET on survival was also investigated in relation to EGFR mutation status.
  
  
  METHODS
  We enrolled 311 patients with resected lung adenocarcinoma (high-risk stage 1B-3A), and performed immunohistochemistry (IHC) using C-MET- and mutant EGFR (EGFRmut)-specific antibodies in tissue microarrays.
  
  
  RESULTS
  Adjuvant chemotherapy was administered to 151 patients, 96 of whom relapsed and 85 died by the end of the study. On IHC, C-MET and EGFRmut were positive in 141 (45.3 %) and 88 (28.3 %) cases, respectively. On univariate analysis, adjuvant chemotherapy prolonged relapse-free survival (RFS) and overall survival (OS) in C-MET(+) patients (RFS p = 0.035; OS p = 0.013) but not in C-MET(-) patients. On multivariate analysis, adjuvant chemotherapy was a positive independent prognostic factor in C-MET(+) (RFS p = 0.013; OS p = 0.006) but not in C-MET(-) patients. In addition, univariate analysis showed no effect of EGFRmut status on RFS and OS after chemotherapy, whereas multivariate analysis revealed that adjuvant chemotherapy increased RFS in both EGFRmut(+) and EGFRmut(-) patients [EGFRmut(+) p = 0.033; EGFRmut(-) p = 0.030]. C-MET was a negative prognostic factor for RFS (p = 0.045) and OS (p = 0.007) in the EGFRmut(-) group but not in the EGFRmut(+) group, on multivariate analysis.
  
  
  CONCLUSIONS
  Our data indicate that patients with C-MET overexpression should be considered for adjuvant chemotherapy, and that C-MET negatively correlates with survival in patients with wild-type, but not mutant, EGFR.
authors.affiliation: Department of Internal Medicine, Division of Medical Oncology, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea.
authors.forename: In-Ho
authors.initials: IH
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Division of Medical Oncology, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea.
authors.forename: In Hee
authors.initials: IH
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Division of Medical Oncology, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea.
authors.forename: Ji Eun
authors.initials: JE
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Division of Medical Oncology, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea.|Multidisciplinary Team of Lung Cancer of Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea.
authors.forename: Sook Hee
authors.initials: SH
authors.lastname: Hong
authors.affiliation: Department of Pathology, Yeouidol St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea.
authors.forename: Tae-Jung
authors.initials: TJ
authors.lastname: Kim
authors.affiliation: Department of Pathology, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea.|Multidisciplinary Team of Lung Cancer of Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea.
authors.forename: Kyo-Young
authors.initials: KY
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Division of Pulmonology, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea.|Multidisciplinary Team of Lung Cancer of Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea.
authors.forename: Young Kyoon
authors.initials: YK
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Division of Pulmonology, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea.|Multidisciplinary Team of Lung Cancer of Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea.
authors.forename: Seung Joon
authors.initials: SJ
authors.lastname: Kim
authors.affiliation: Department of Thoracic Surgery, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea.|Multidisciplinary Team of Lung Cancer of Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea.
authors.forename: Sook Whan
authors.initials: SW
authors.lastname: Sung
authors.affiliation: Department of Thoracic Surgery, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea.|Multidisciplinary Team of Lung Cancer of Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea.
authors.forename: Jae Kil
authors.initials: JK
authors.lastname: Park
authors.affiliation: Department of Nuclear Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea.|Multidisciplinary Team of Lung Cancer of Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea.
authors.forename: Ie Ryung
authors.initials: IR
authors.lastname: Yoo
authors.affiliation: Department of Radiation Oncology, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea.|Multidisciplinary Team of Lung Cancer of Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea.
authors.forename: Yeon Sil
authors.initials: YS
authors.lastname: Kim
authors.affiliation: Department of Biomedical Sciences, The Catholic University of Korea, Seoul, Korea.
authors.forename: Jung-Oh
authors.initials: JO
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Division of Medical Oncology, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea. jinkang@catholic.ac.kr.|Multidisciplinary Team of Lung Cancer of Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea. jinkang@catholic.ac.kr.
authors.forename: Jin Hyoung
authors.initials: JH
authors.lastname: Kang
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism* / Q000556:secondary / Q000628:therapy*; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000008:administration & dosage; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000235:genetics* / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D017239:Paclitaxel / Q000008:administration & dosage; D011013:Pneumonectomy; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism*; D012189:Retrospective Studies; D015996:Survival Rate; D014747:Vinblastine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000077235:Vinorelbine
chemical_list: D014747:Vinblastine; D016190:Carboplatin; D066246:ErbB Receptors; D019859:Proto-Oncogene Proteins c-met; D017239:Paclitaxel; D002945:Cisplatin; D000077235:Vinorelbine