title: Prognostic implication of EGFR, KRAS, and TP53 gene mutations in a large cohort of Japanese patients with surgically treated lung adenocarcinoma.
abstract: BACKGROUND
  Although mutation of the epidermal growth factor receptor (EGFR) gene is predictive for the response to EGFR-tyrosine kinase inhibitor, its prognostic impact for patients without EGFR-tyrosine kinase inhibitor treatment remains controversial. We examined for EGFR, KRAS or TP53 mutations in a consecutive large cohort of patients with lung adenocarcinoma, and evaluated their prognostic impact.
  
  
  METHODS
  We analyzed 397 patients with lung adenocarcinoma who underwent potentially curative pulmonary resection. Total ribonucleic acid was extracted and direct sequencing of each gene was performed after reverse transcription-polymerase chain reaction.
  
  
  RESULTS
  We found that 196 patients (49%) had EGFR mutations. Of these, 83 were exon 19 deletions (42%) and 92 were L858R (47%). Univariate analysis showed that patients with EGFR mutations survived for a longer period than those without mutations (p = 0.0046). However, there was no difference in overall survival between the patients with exon 19 deletion and those with L858R (p = 0.4144). Patients with KRAS mutations or TP53 mutations tended to survive for a shorter period (p = 0.2183 and 0.0230, respectively). Multivariate analysis using the Cox proportional hazards model revealed that smoking status (p = 0.0310) and disease stage (p < 0.0001) were independent prognostic factors. However, none of the gene mutations was independent prognostic factors (EGFR, p = 0.3225; KRAS, p = 0.8500; TP53, p = 0.3191).
  
  
  CONCLUSIONS
  EGFR, KRAS, and TP53 gene mutations were not independently associated with the prognosis for Japanese patients with surgically treated lung adenocarcinoma.
authors.affiliation: Department of Thoracic Surgery, Aichi Cancer Center Hospital, Nagoya, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Kosaka
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Yatabe
authors.forename: Ryoichi
authors.initials: R
authors.lastname: Onozato
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kuwano
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Mitsudomi
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000556:secondary / Q000601:surgery; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000595:Amino Acid Sequence; D002454:Cell Differentiation; D015331:Cohort Studies; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D009367:Neoplasm Staging; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D012907:Smoking; D015996:Survival Rate; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism; D018631:ras Proteins / Q000235:genetics*
chemical_list: C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C512478:EGFR protein, human; D066246:ErbB Receptors; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins