Correlation of EGFR mutations with chromosomal alterations and expression of EGFR, ErbB3 and VEGF in tumor samples of lung adenocarcinoma patients

• Published in: Lung cancer (Amsterdam, Netherlands) Netherlands), 2008-11, Vol.62 (2), p.193-201
• Main Authors: Reinmuth, Niels, Jauch, Anna, Xu, Elizabeth Chang, Muley, Thomas, Granzow, Martin, Hoffmann, Hans, Dienemann, Hendrik, Herpel, Esther, Schnabel, Philipp A, Herth, Felix J.F, Gottschling, Sandra, Lahm, Harald, Steins, Martin, Thomas, Michael, Meister, Michael
• Format: Article
• Language: English
• Subjects: Adenocarcinoma; Adenocarcinoma - genetics; Biological and medical sciences; Chromosome Aberrations; Comparative Genomic Hybridization; DNA Mutational Analysis; EGFR mutation; Female; Hematology, Oncology and Palliative Medicine; Humans; Immunohistochemistry; Lung Neoplasms - genetics; Male; Medical sciences; Mutation; Non-small cell lung cancer; Pneumology; Pulmonary/Respiratory; Receptor, Epidermal Growth Factor - biosynthesis; Receptor, Epidermal Growth Factor - genetics; Receptor, ErbB-3 - biosynthesis; Tumors; Tumors of the respiratory system and mediastinum; Vascular Endothelial Growth Factor A - biosynthesis; VEGF expression
• ISSN: 0169-5002; 1872-8332
• DOI: 10.1016/j.lungcan.2008.03.011

Summary Introduction Mutations in the tyrosine kinase domain of the epidermal growth factor receptor (EGFR) are frequently detected in lung adenocarcinomas with bronchioloalveolar (BAC) differentiation and have been associated with increased response to small molecule EGFR inhibitors in some clinical studies. However, further molecular characterization of tumor cells carrying EGFR mutations (EGFR-mut) is warranted. Methods By DNA sequencing, 120 patients with lung adenocarcinomas (70 tumors with BAC components) were screened for EGFR mutations within exons 18–21. Performing comparative genomic hybridization (CGH) and immunohistochemistry, chromosomal imbalances and protein expression levels of EGFR, ErbB3 and VEGF (vascular endothelial growth factor) were analyzed, respectively. Results EGFR mutations were detected in 20/120 tumors. Tumors with BAC components carried more frequently EGFR mutations compared to adenocarcinomas without BAC histology (17/70 = 24% vs 3/50 = 6.0%; p = 0.012). In a subsequent matched-pair analysis, CGH-analysis demonstrated similar mean numbers of chromosomal imbalances for EGFR mutated and wild-type tumors (8.6 vs 7.8 gains; 2.4 vs 2.7 losses), respectively. Furthermore, tumors with mutated EGFR demonstrated gains in chromosomes 7p, 16p and 20q and losses in chromosome 8p. Interestingly, EGFR mutated tumors showed higher VEGF expression ( p = 0.03) while differences in EGFR expression were not statistically significant. Conclusion EGFR gene mutations are frequently seen in lung adenocarcinomas with BAC differentiation and can be linked to chromosomal imbalances and increased VEGF expression.