title: Tumor gene mutations and messenger RNA expression: correlation with clinical response to icotinib hydrochloride in non-small cell lung cancer.
abstract: BACKGROUND
  Molecular targeted drugs is now widely used in non-small cell lung cancer (NSCLC) clinical treatment. Icotinib hydrochloride is a new type of oral epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (EGFR-TKIs). In this study, we examined the role of EGFR, K-RAS, B-RAF somatic mutations and EGFR mRNA expression in tumor specimens from advanced NSCLC patients as predicators of the efficacy of icotinib hydrochloride.
  
  
  METHODS
  We analyzed tumor paraffin-embedded specimens, which were obtained from 14 of 40 patients with advanced NSCLC who enrolled in the stage I clinical trial of icotinib hydrochloride. Somatic mutations were evaluated by mutant-enriched liquidchip (MEL) technology, and EGFR mRNA expression was measured by branched DNA liquidchip (MBL) technology.
  
  
  RESULTS
  In the 14 specimens, seven patients showed EGFR mutations, exon 19 deletion (3/7) and exon 21 point mutation (4/7); and two patients showed K-RAS mutation. No mutations in EGFR exon 20 or B-RAF were detected. In patients with EGFR mutation, one patient developed progress disease (PD), three patients had stable disease (SD), two patients had partial responses (PR) and one patient had a complete response (CR). In patients with wild-type EGFR, four patients had PD, three patients acquired SD, and none had PR/CR (P = 0.0407). EGFR mutations were associated with better progress-free survival (PFS) (141 days vs. 61 days) but without a statistically significant difference (P = 0.8597), and median overall survival (OS) (≥ 449 days vs. 140 days). EGFR mRNA expression levels were evaluated (three high, eight moderate, one low, and two that can not be measured due to insufficient tumor tissue) and no statistically significant relationships was observed with response, PFS or OS.
  
  
  CONCLUSIONS
  The EGFR mutation rate was consistent with that reported in the Asian population, so the MEL technology is reliable for measuring EGFR mutation with high throughput and rapidity. EGFR exon 19 deletions and exon 21 point mutation are predictive biomarkers for response to icotinib hydrochloride as second line treatment or above.
authors.affiliation: Department of Respiration, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing 100730, China.
authors.forename: Guan-Jun
authors.initials: GJ
authors.lastname: Ren
authors.forename: Yuan-Yuan
authors.initials: YY
authors.lastname: Zhao
authors.forename: Yu-Jia
authors.initials: YJ
authors.lastname: Zhu
authors.forename: Yi
authors.initials: Y
authors.lastname: Xiao
authors.forename: Jia-Sen
authors.initials: JS
authors.lastname: Xu
authors.forename: Bin
authors.initials: B
authors.lastname: Shan
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics*; D043844:Crown Ethers / Q000627:therapeutic use*; D066246:ErbB Receptors / Q000235:genetics*; D005091:Exons / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics; D011799:Quinazolines / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000235:genetics*
chemical_list: D000970:Antineoplastic Agents; D043844:Crown Ethers; D011799:Quinazolines; D012333:RNA, Messenger; C531470:icotinib; D066246:ErbB Receptors; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D016283:Proto-Oncogene Proteins p21(ras)