title: Primary concomitant EGFR T790M mutation predicted worse prognosis in non-small cell lung cancer patients.
abstract: OBJECTIVE
  We performed this analysis to improve the understanding of the clinicopathological characteristics and clinical outcome of non-small cell lung cancer (NSCLC) patients harboring the primary epidermal growth factor receptor (EGFR) T790M mutation along with activating EGFR mutation.
  
  
  METHODS
  Resected tumors from 1903 NSCLC patients were analyzed for mutation in EGFR, as well as KRAS (Kirsten rat sarcoma viral oncogene homolog), BRAF (v-raf murine sarcoma viral oncogene homolog B), HER2 (human epidermal growth factor 2), PIK3CA (phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha), and EML4 (echinoderm microtubule associated protein like 4)-ALK (anaplastic lymphoma receptor tyrosine kinase) fusion. Fluorescence in situ hybridization was performed to define EGFR and c-MET (met proto-oncogene gene amplification. Expression of PIK3CA and p-Akt (phosphorylated protein kinase B) were tested using immunohistochemistry. Clinical and pathological data, including sex, age at diagnosis, stage, tumor differentiation, smoking history, histological subtype, relapse-free and overall survival, were further analyzed.
  
  
  RESULTS
  In all, 16 NSCLC patients were found to harbor primary EGFR T790M mutation, including 14 adenocarcinomas and two adenosquamous carcinomas, accounting for 2.04% of all the EGFR mutant cases and 0.84% of the total. No c-MET amplification was found to coexist with primary EGFR T790M. Fewer EGFR copy-number variations were found in samples harboring EGFR T790M mutations compared with those in patients with exon 19 deletions and L858R. Overall survival was significantly shorter for patients harboring EGFR T790M mutation than it was for patients with exon 19 deletions (logrank P=0.008). When taking patients harboring EGFR L858R or exon 19 deletions as one group, the overall survival was also significantly longer than that in patients with T790M mutation (logrank P=0.012). There was no significant difference in relapse-free survival among three subgroups of patients.
  
  
  CONCLUSIONS
  Our study described the clinicopathological and molecular characteristics of NSCLC patients harboring primary EGFR T790M mutations. Its value of being a predictor for worse prognosis was established. Primary EGFR T790M mutation is a rare event in NSCLC cases, but the therapeutic strategies for this subtype of patients should be precisely considered.
authors.affiliation: Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China ; Department of Oncology, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China.
authors.forename: Hang
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China ; Department of Oncology, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China.
authors.forename: Haichuan
authors.initials: H
authors.lastname: Hu
authors.affiliation: Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China ; Department of Oncology, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China.
authors.forename: Rui
authors.initials: R
authors.lastname: Wang
authors.affiliation: Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China ; Department of Oncology, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China.
authors.forename: Yunjian
authors.initials: Y
authors.lastname: Pan
authors.affiliation: Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China ; Department of Oncology, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China.
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Oncology, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China ; Department of Pathology, Shanghai Medical College, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China ; Department of Oncology, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China ; Department of Oncology, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China.
authors.forename: Ting
authors.initials: T
authors.lastname: Ye
authors.affiliation: Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China ; Department of Oncology, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China.
authors.forename: Yiliang
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China ; Department of Oncology, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China.
authors.forename: Bin
authors.initials: B
authors.lastname: Li
authors.affiliation: Department of Oncology, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China ; Department of Pathology, Shanghai Medical College, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China.
authors.forename: Lei
authors.initials: L
authors.lastname: Shen
authors.affiliation: Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China ; Department of Oncology, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China.
authors.forename: Yihua
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China ; Department of Oncology, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China.
authors.forename: Haiquan
authors.initials: H
authors.lastname: Chen
keywords: EGFR tyrosine kinase inhibitor; acquired resistance; clinicopathological profile; driver mutation; survival
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