title: EGFR and KRAS mutations in lung carcinomas in the Dutch population: increased EGFR mutation frequency in malignant pleural effusion of lung adenocarcinoma.
abstract: BACKGROUND
  Frequencies of EGFR and KRAS mutations in non-small cell lung cancer (NSCLC) have predominantly been determined in East Asian and North American populations, showing large differences between these populations. The aim of the present study was to determine the frequency of EGFR and KRAS mutations in NSCLC in the West European Dutch population in primary carcinomas and different metastatic locations.
  
  
  METHODS
  EGFR (exons 19, 20 and 21) and KRAS (exons 2 and 3) mutation test results of NSCLC samples of patients in 13 hospitals were collected. The tests were performed on paraffin-embedded tissue or cytological material of primary and metastatic lung carcinomas.
  
  
  RESULTS
  EGFR mutations were detected in 71/778 (9.1 %) tested patients; in 66/620 (10.6 %) adenocarcinomas. EGFR mutations were significantly more often detected in female than in male patients (13.4 % vs. 5.5 %, p < 0.001). KRAS mutations were found in 277 out of 832 (33.3 %) tested patients; in 244/662 (36.9 %) adenocarcinomas. A significantly increased frequency of EGFR mutations was observed in patients with malignant pleural/pericardial effusions (26.5 %; odds ratio (OR) 2.80, 95 % confidence interval (CI) 1.22-6.41), whereas the frequency of KRAS mutations was significantly decreased (18.8 %; OR 0.35, 95 % CI 0.14-0.86).
  
  
  CONCLUSIONS
  In the investigated Dutch cohort, patients with malignant pleural/pericardial effusion of lung adenocarcinoma have an increased frequency of EGFR mutations. The overall frequency of EGFR mutations in lung adenocarcinomas in this West European population is within the frequency range of North American and South European populations, whereas KRAS mutation frequency is higher than in any population described to date.
authors.affiliation: Department of Pathology, St. Antonius Hospital, Nieuwegein, The Netherlands.
authors.forename: Alexander J J
authors.initials: AJ
authors.lastname: Smits
authors.forename: J Alain
authors.initials: JA
authors.lastname: Kummer
authors.forename: John W J
authors.initials: JW
authors.lastname: Hinrichs
authors.forename: Gerarda J M
authors.initials: GJ
authors.lastname: Herder
authors.forename: Karen C
authors.initials: KC
authors.lastname: Scheidel-Jacobse
authors.forename: N Mehdi
authors.initials: NM
authors.lastname: Jiwa
authors.forename: T Emiel G
authors.initials: TE
authors.lastname: Ruijter
authors.forename: Peet T G A
authors.initials: PT
authors.lastname: Nooijen
authors.forename: Monica G
authors.initials: MG
authors.lastname: Looijen-Salamon
authors.forename: Marjolijn J L
authors.initials: MJ
authors.lastname: Ligtenberg
authors.forename: Frederik B
authors.initials: FB
authors.lastname: Thunnissen
authors.forename: Daniëlle A M
authors.initials: DA
authors.lastname: Heideman
authors.forename: Roel A
authors.initials: RA
authors.lastname: de Weger
authors.forename: Aryan
authors.initials: A
authors.lastname: Vink
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics*; D000077192:Adenocarcinoma of Lung; D066246:ErbB Receptors / Q000235:genetics*; D005091:Exons / Q000235:genetics; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D059645:Mutation Rate; D009362:Neoplasm Metastasis / Q000235:genetics; D009426:Netherlands; D016066:Pleural Effusion, Malignant / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins / Q000235:genetics*
chemical_list: C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; C512478:EGFR protein, human; D066246:ErbB Receptors; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins