title: [Correlation of clinicopathologic features and driver gene mutation in non-small cell lung cancer].
abstract: OBJECTIVE
  To study the relationship between mutations of well-known driver genes and clinicopathologic characteristics of non-small cell lung cancers (NSCLC).
  
  
  METHODS
  Scorpions amplification refractory mutation system (scorpions ARMS) fluorescence quantitative PCR was performed to investigate 205 driver gene mutation status in NSCLC in correlation with clinicopathological characteristics of the patients.
  
  
  RESULTS
  Driver gene mutations were detected in 146 of 205 (71.2%) patients with NSCLC, including 81.7%(138/169) adenocarcinomas, in which mutations of nine genes were found: EGFR (63.3%, 107/169), KRAS (5.9%, 10/169), PIK3CA (4.1%, 7/169), ALK (4.1%, 7/169), ROS1 (3.0%, 5/169), RET (3.6%, 6/169), HER2 (1.8%, 3/169), NRAS (0.6%, 1/169) and BRAF (0.6%, 1/169). The frequencies of driver gene mutations were higher in adenocarcinomas, female patients and non-smokers (P<0.01, P=0.003, P<0.01, respectively). Driver gene mutation status showed no correlation with either the age or the clinical stage (P=0.281, P=0.490, respectively). However, EGFR mutations tended to occur in adenocarcinoma, female, non-smokers, and patients of ≥62 years of age (P<0.01, P<0.01, P=0.002, P=0.012, respectively). The frequency of EGFR mutation was positively correlated with the tumor histology of lepidic, acinar, papillary and micropapillary predominant growth patterns. There was no relationship between EGFR mutation and the clinical stage (P=0.237). The frequency of KRAS mutation was higher in solid predominant and invasive mucinous adenocarcinomas (P=0.015); that of PIK3CA mutation was higher in patients of ≥62 years of age, invasive mucinous adenocarcinoma and fetal adenocarcinoma (P=0.015, P=0.006, respectively). ALK, ROS1 or RET mutation positive NSCLC tended to occur in nonsmokers and have solid predominant tumors and invasive mucinous adenocarcinoma (P=0.012, P=0.017 respectively). The frequency of EML4-ALK mutation was higher in the early stage patients with solid predominant tumors and invasive mucinous adenocarcinomas (P=0.025, P=0.014, respectively); that of ROS1 rearrangement was higher in invasive mucinous adenocarcinomas (P=0.049). NRAS, BRAF and HER2 gene mutations were infrequent and their clinical significance remained to be elucidated.
  
  
  CONCLUSIONS
  The relationship between mutations of well-known driver genes and clinicopathological characteristics in patients with NSCLC has diversity, the rate of mutations is higher in non-smoking female patients with adenocarcinoma.
authors.affiliation: Department of Pathology, Fujian Provincial Hospital, Fuzhou 350001, China.
authors.forename: L F
authors.initials: LF
authors.lastname: Chen
authors.forename: X Y
authors.initials: XY
authors.lastname: Chen
authors.forename: X B
authors.initials: XB
authors.lastname: Yu
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology; D002288:Adenocarcinoma, Mucinous / Q000235:genetics / Q000473:pathology; D000077548:Anaplastic Lymphoma Kinase; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology*; D058534:Class I Phosphatidylinositol 3-Kinases; D066246:ErbB Receptors; D005260:Female; D020558:GTP Phosphohydrolases / Q000235:genetics; D018773:Genes, erbB-1; D018734:Genes, erbB-2; D011905:Genes, ras; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D009154:Mutation; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics; D011505:Protein-Tyrosine Kinases / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics
chemical_list: D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases; D051096:Proto-Oncogene Proteins c-ret; C099282:RET protein, human; C062333:ROS1 protein, human; D020794:Receptor Protein-Tyrosine Kinases; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D020558:GTP Phosphohydrolases; C579846:NRAS protein, human