Increased EGFR mRNA expression levels in non-small cell lung cancer in a Turkish population

Abstract

Objective: In this study, we investigated the frequency of EGFR gene mutations, the level of EGFR mRNA and protein expressions in Turkish population for indicating substantial differences in the frequency of EGFR mutations, EGFR amplification and EGFR protein expression between populations and the effect of these parameters in response to EGFR tyrosine kinase inhibitors. Materials and Methods:The study included 34 patients with non-small cell lung cancers. The RNA and DNA were extracted from the normal and tumor side of the lung tissue removed by surgery. To investigate the most common mutations in the EGFR gene, exon 19 was sequenced and mutation specific PCR was performed for detecting the L858R mutation in exon 21. EGFR mRNA expression was measured by relative quantitative reverse transcription PCR. The EGFR protein levels were detected with immunohistochemistry methods from the sections of the patients' paraffin blocks.Results: No EGFR mutation in exon 19 or L858R mutation in exon 21 were detected in the patients. Overexpression of EGFR gene mRNA was identified in 16 of 34 (%47) patients and overexpression of EGFR protein was detected in 15 of 34 (%44) patients. Statistical analysis was not significant for the correlation between sex, age, smoking, histopathology, pathological stage and overexpression of EGFR mRNA and protein.Conclusion: It was found that in Turkish population, EGFR mutation in exon 19 and L858R mutation were very rare, EGFR protein expression was similar and EGFR mRNA expression significantly increased compared to the literature. Markedly increased EGFR mRNA expression ratios in the absence of activating mutations showed that identifying the EGFR mRNA expression level for prediction of response to EGFR tyrosine kinase inhibitors might be significant in the Turkish population.Keywords: NSCLC, EGFR, mutation, mRNA, protein, Turkey ÖZ Amaç: Toplumlar arasında farklı oranlarda EGFR mutasyonları, EGFR amplifikasyonları ve EGFR protein ekspresyonları görülmesi ve bunların EGFR tirozin kinaz inhibitörlerine cevapta etkili olması nedeniyle bu çalışmada Türk toplumunda EGFR gen mutasyonlarının sıklığı, EGFR mRNA ve protein ekspresyon düzeyi incelendi.Gereç ve Yöntem: Çalışma Küçük Hücreli Olmayan Akciğer Kanseri nedeniyle opere edilen 34 hasta ile yapıldı. Cerrahi rezeksiyonla çıkartılan akciğer dokusunun, kanserli ve kanserli olmayan kısımlarından örnek alınarak RNA ve DNA ları elde edildi. EGFR geninde en sık görülen mutasyonları araştırmak için; exon 19 sekanslandı, exon 21 deki L858R mutasyonunu tespit etmek için mutasyona spesifik PZR yapıldı. Hastaların EGFR mRNA expresyon düzeyi relatif kantitatif revers transkriptaz PZR ile ölçüldü. Hastaların parafinli dokularından alınan kesitlerde immunohistokimsayal yöntemle EGFR protein düzeyi belirlendi.Bulgular: Hastaların hiçbirinde EGFR geninde exon 19 veya L858R mutasyonları tespit edilemedi. İn-celenen 34 olgunun 16 (%47) sında EGFR geni mRNA ekspresyon ve 15 (%44) inde ise EGFR protein ekspresyon artışı belirlendi. EGFR geninin mRNA ve pr...