title: The frequency of EGFR and KRAS mutations in non-small cell lung cancer (NSCLC): routine screening data for central Europe from a cohort study.
abstract: OBJECTIVE
  Owing to novel therapy strategies in epidermal growth factor receptor (EGFR)-mutated patients, molecular analysis of the EGFR and KRAS genome has become crucial for routine diagnostics. Till date these data have been derived mostly from clinical trials, and thus collected in pre-selected populations. We therefore screened 'allcomers' with a newly diagnosed non-small cell lung carcinoma (NSCLC) for the frequencies of these mutations.
  
  
  METHODS
  A cohort study.
  
  
  METHODS
  Lung cancer centre in a tertiary care hospital.
  
  
  METHODS
  Within 15 months, a total of 552 cases with NSCLC were eligible for analysis.
  
  
  METHODS
  Frequency of scrutinising exons 18, 19 and 21 for the presence of activating EGFR mutation and secondary codon 12 and 13 for activating KRAS mutations.
  
  
  RESULTS
  Of the 552 patients, 27 (4.9%) showed a mutation of EGFR. 19 of these patients (70%) had deletion E746-A750 in codon 19 or deletion L858R in codon 21. Adenocarcinoma (ACA) was the most frequent histology among patients with EGFR mutations (ACA, 22/254 (8.7%) vs non-ACA, 5/298 (1.7%); p<0.001). Regarding only ACA, the percentage of EGFR mutations was higher in women (16/116 (14%) women vs 6/138 (4.3%) men; p=0.008). Tumours with an activating EGFR mutation were more likely to be from non-smokers (18/27; 67%) rather than smoker (9/27; 33%). KRAS mutation was present in 85 (15%) of all cases. In 73 patients (86%), the mutation was found in exon 12 and in 12 cases (14%) in exon 13. Similarly, ACA had a higher frequency of KRAS mutations than non-ACA (67/254 (26%) vs 18/298 (6.0%); p<0.001).
  
  
  CONCLUSIONS
  We found a lower frequency for EGFR and KRAS mutations in an unselected Caucasian patient cohort as previously published. Taking our results into account, clinical trials may overestimate the mutation frequency for EGFR and KRAS in NSCLC due to important selection biases.
authors.affiliation: Klinik für Pneumologie, Lungenklinik Heckeshorn, HELIOS Klinikum Emil von Behring, Berlin, Berlin, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Boch
authors.forename: Jens
authors.initials: J
authors.lastname: Kollmeier
authors.forename: Andreas
authors.initials: A
authors.lastname: Roth
authors.forename: Susann
authors.initials: S
authors.lastname: Stephan-Falkenau
authors.forename: Daniel
authors.initials: D
authors.lastname: Misch
authors.forename: Wolfram
authors.initials: W
authors.lastname: Grüning
authors.forename: Torsten Thomas
authors.initials: TT
authors.lastname: Bauer
authors.forename: Thomas
authors.initials: T
authors.lastname: Mairinger
references.citation: N Engl J Med. 2009 Sep 3;361(10):947-57
references.pmid: 19692680
references.citation: J Clin Oncol. 2010 Feb 20;28(6):918-27
references.pmid: 20100958
references.citation: Cancer. 2001 Sep 15;92(6):1525-30
references.pmid: 11745231
references.citation: J Thorac Oncol. 2007 May;2(5):430-9
references.pmid: 17473659
references.citation: Oncol Rep. 2009 Oct;22(4):683-91
references.pmid: 19724844
references.citation: J Clin Oncol. 2010 Feb 10;28(5):744-52
references.pmid: 20038723
references.citation: J Thorac Oncol. 2008 Dec;3(12):1446-53
references.pmid: 19057271
references.citation: Eur Respir J. 2012 Jul;40(1):177-84
references.pmid: 22267755
references.citation: Cancer Lett. 2006 Aug 8;239(2):292-7
references.pmid: 16243431
references.citation: J Thorac Oncol. 2006 Nov;1(9 Suppl):S13-9
references.pmid: 17409995
references.citation: N Engl J Med. 2004 May 20;350(21):2129-39
references.pmid: 15118073
references.citation: Lancet. 2009 May 2;373(9674):1525-31
references.pmid: 19410716
references.citation: Oncol Rep. 2009 Nov;22(5):1013-20
references.pmid: 19787214
references.citation: Am J Clin Pathol. 2007 Jul;128(1):100-8
references.pmid: 17580276
references.citation: J Clin Oncol. 2005 Sep 1;23(25):5900-9
references.pmid: 16043828
references.citation: Clin Cancer Res. 2007 May 15;13(10):2890-6
references.pmid: 17504988
references.citation: Cancer Epidemiol Biomarkers Prev. 1997 Oct;6(10):841-7
references.pmid: 9332768
references.citation: J Clin Oncol. 2011 Nov 1;29(31):4113-20
references.pmid: 21969500
references.citation: Lancet Oncol. 2011 Aug;12(8):735-42
references.pmid: 21783417
references.citation: Anticancer Res. 2010 Dec;30(12):5121-8
references.pmid: 21187500
references.citation: N Engl J Med. 2009 Sep 3;361(10):958-67
references.pmid: 19692684
references.citation: Lung Cancer. 2011 Nov;74(2):274-9
references.pmid: 21439671
references.citation: Nat Rev Cancer. 2007 Mar;7(3):169-81
references.pmid: 17318210
references.citation: Tob Control. 2011 Jan;20(1):e4
references.pmid: 20966129
references.citation: Pathologe. 2009 Sep;30(5):384-92
references.pmid: 19357847
references.citation: CA Cancer J Clin. 2010 Sep-Oct;60(5):277-300
references.pmid: 20610543
references.citation: Ann Oncol. 2007 Apr;18(4):752-60
references.pmid: 17317677
references.citation: J Natl Cancer Inst. 1999 Dec 1;91(23):2032-8
references.pmid: 10580029
references.citation: J Thorac Oncol. 2011 Jan;6(1):28-31
references.pmid: 21107288
references.citation: Ann Oncol. 2007 Jan;18(1):99-103
references.pmid: 17060486
references.citation: Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463-7
references.pmid: 271968
references.citation: Environ Mol Mutagen. 2012 Jan;53(1):78-82
references.pmid: 22223435