Epidermal Growth Factor Receptor Mutations in 510 Finnish Non–Small-Cell Lung Cancer Patients

Introduction: Among the driver gene mutations in non–small-cell lung cancer, mutations in epidermal growth factor receptor (EGFR) are the most important because of their predictive role in selecting patients eligible for targeted therapy. Our aim was to study EGFR mutations in a Finnish non–small-cell lung cancer cohort of 528 patients. Methods: Mutation testing was conducted on DNA extracted from paraffin-embedded, formalin-fixed tumor material using the following real-time polymerase chain reaction-based kits: Therascreen EGFR PCR Kit and cobas EGFR Mutation Test. Results: EGFR mutation frequency was 11.4% and all positive cases were adenocarcinomas, of which a majority had an acinar predominant pattern. Mutations were seen significantly more often in females and never-smokers than in males and smokers. The most frequent mutations were L858R in exon 21 and deletions in exon 19. Overall survival of the patients, not treated with EGFR inhibitor, did not differ between EGFR mutation-positive and EGFR mutation-negative patients. Conclusion: EGFR mutation profile in this Finnish non–small-cell lung cancer cohort resembles in many respect with that of other Western European cohorts, even though the overall frequency of mutations is slightly higher. We show the occurrence of EGFR mutations in patients with occupational asbestos exposure and also in those diagnosed with chronic obstructive pulmonary disease who have not been often investigated before.

[1]  J. Andrews,et al.  Comparison of Targeted Next‐Generation Sequencing (NGS) and Real‐Time PCR in the Detection of EGFR, KRAS, and BRAF Mutations on Formalin‐Fixed, Paraffin‐Embedded Tumor Material of Non‐Small Cell Lung Carcinoma—Superiority of NGS , 2013, Genes, chromosomes & cancer.

[2]  T. Mairinger,et al.  The frequency of EGFR and KRAS mutations in non-small cell lung cancer (NSCLC): routine screening data for central Europe from a cohort study , 2013, BMJ Open.

[3]  P. Russell,et al.  Correlation of Mutation Status and Survival with Predominant Histologic Subtype According to the New IASLC/ATS/ERS Lung Adenocarcinoma Classification in Stage III (N2) Patients , 2013, Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer.

[4]  C. Kang,et al.  The Presence of Mutations in Epidermal Growth Factor Receptor Gene Is Not a Prognostic Factor for Long-Term Outcome after Surgical Resection of Non–Small-Cell Lung Cancer , 2013, Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer.

[5]  M. Ladanyi,et al.  Association of KRAS and EGFR mutations with survival in patients with advanced lung adenocarcinomas , 2013, Cancer.

[6]  Y. Li,et al.  Clinical Significance of EML4-ALK Fusion Gene and Association with EGFR and KRAS Gene Mutations in 208 Chinese Patients with Non-Small Cell Lung Cancer , 2013, PloS one.

[7]  C. Couture,et al.  Immunohistochemistry is a Reliable Screening Tool for Identification of ALK Rearrangement in Non–Small-Cell Lung Carcinoma and is Antibody Dependent , 2013, Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer.

[8]  S. Kobayashi,et al.  Compound EGFR Mutations and Response to EGFR Tyrosine Kinase Inhibitors , 2013, Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer.

[9]  Yang Zhang,et al.  Frequency of well-identified oncogenic driver mutations in lung adenocarcinoma of smokers varies with histological subtypes and graduated smoking dose. , 2013, Lung cancer.

[10]  M. Ligtenberg,et al.  EGFR and KRAS mutations in lung carcinomas in the Dutch population: increased EGFR mutation frequency in malignant pleural effusion of lung adenocarcinoma , 2012, Cellular Oncology.

[11]  Charles A Powell,et al.  International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society: international multidisciplinary classification of lung adenocarcinoma: executive summary. , 2011, Proceedings of the American Thoracic Society.

[12]  L. Kleinberg,et al.  EGFR Gene Alterations in a Norwegian Cohort of Lung Cancer Patients Selected for Surgery , 2011, Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer.

[13]  Masahiro Tsuboi,et al.  International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society International Multidisciplinary Classification of Lung Adenocarcinoma , 2011, Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer.

[14]  K. Kunimasa,et al.  Complex Mutations in the Epidermal Growth Factor Receptor Gene in Non-small Cell Lung Cancer , 2010, Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer.

[15]  Y. Yatabe,et al.  Epidermal growth factor receptor in relation to tumor development: EGFR gene and cancer , 2010, The FEBS journal.

[16]  Lin Huan,et al.  Screening for Epidermal Growth Factor Receptor Mutations in Lung Cancer , 2010 .

[17]  Mariano Provencio,et al.  Screening for epidermal growth factor receptor mutations in lung cancer. , 2009, The New England journal of medicine.

[18]  J. Park,et al.  EGFR, ERBB2, and KRAS mutations in Korean non-small cell lung cancer patients. , 2007, Cancer genetics and cytogenetics.