title: Significance of EGFR signaling pathway genetic alterations in radically resected non-small cell lung cancers from a Polish cohort. One institutional study.
abstract: OBJECTIVE
  We evaluated the distribution and clinical impact of EGFR, KRAS and HER2 copy number gains and EGFR, KRAS and BRAF activating mutations in resected non-small cell lung cancers (NSCLCs) from 151 Polish patients.
  
  
  METHODS
  Quantitative PCR and DNA sequencing were used for copy number evaluation and mutational analysis, respectively.
  
  
  RESULTS
  An increased EGFR CN was found in 21.2% of the tumors, more commonly of the non-squamous histology (P=0.029), larger in size (P=0.004) and those obtained from women (P=0.040). HER2 copy gain was observed in 21.8% of the patients, more frequently with lymph node metastases (P=0.048) and stage IIIA disease (P=0.061). KRAS gain was found in 29.3% of the tumors, and was not associated with patients' clinicopathological features. No BRAF mutations were found. EGFR and KRAS mutation frequency and associations with clinicopathological characteristics did not differ significantly from those previously described for the NSCLC patients of Caucasian ethnicity. Strong associations existed between most of the analyzed alterations. In the multivariate model, EGFR mutations constituted an independent prognostic factor of the disease recurrence in adenocarcinoma patients (HR 7.20; 95%CI 1.31-39.48; P=0.023), while an increased EGFR copy number tended to indicate a shorter overall survival (HR 4.85; 95%CI 0.92-25.58; P=0.062).
  
  
  CONCLUSIONS
  EGFR pathway genes alterations are frequent in NSCLCs from Polish patients and have a prognostic potential for patients' clinical outcome after a curative tumor resection. Gene CN evaluation by quantitative PCR provides comparable results and enables assay standardization, yet the optimal scoring system needs to be developed.
authors.affiliation: Department of Clinical Molecular Biology, Medical University of Bialystok, Poland. Electronic address: okowal@poczta.onet.pl.
authors.forename: Oksana
authors.initials: O
authors.lastname: Kowalczuk
authors.affiliation: Department of Thoracic Surgery, Medical University of Bialystok, Poland.
authors.forename: Miroslaw
authors.initials: M
authors.lastname: Kozlowski
authors.affiliation: Department of Statistics and Medical Informatics, Medical University of Bialystok, Poland.
authors.forename: Robert
authors.initials: R
authors.lastname: Milewski
authors.affiliation: Department of Pulmonology, Medical University of Bialystok, Poland.
authors.forename: Lukasz
authors.initials: L
authors.lastname: Minarowski
authors.affiliation: Department of Medical Pathomorphology, Medical University of Bialystok, Poland.
authors.forename: Joanna
authors.initials: J
authors.lastname: Reszec
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics*; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D011044:Poland; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics; D012189:Retrospective Studies
chemical_list: D066246:ErbB Receptors; D016283:Proto-Oncogene Proteins p21(ras); D018719:Erb-b2 Receptor Tyrosine Kinases; C117307:KRAS protein, human; C508053:ERBB2 protein, human
keywords: EGFR mutations; Gene copy gain; KRAS mutations; NSCLC