Epidermal growth factor receptor and KRAS mutations in lung adenocarcinoma: a retrospective study of the Lebanese population

Najla Fakhruddin 1Rami Mahfouz 1Fadi Farhat 2Arafat Tfayli 3Rabab Abdelkhalik 1Mark Jabbour 1Lamis Yehia 4Ziyad Mahfoud 5Ghazi Zaatari 1

Affiliations

1Department of Pathology and Laboratory Medicine, American University of Beirut Medical Center, Beirut, Lebanon.

2Department of Hematology-Oncology, Hammoud Hospital University Medical Center, Sidon, Lebanon.

3Department of Hematology-Oncology, American University of Beirut Medical Center, Beirut, Lebanon.

4Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH, USA.

5Department of Public Health, Weill Cornell Medical College, Doha, Qatar.

PMID: 25120214

 DOI: 10.3892/or.2014.3406

Abstract

Molecular genetic analysis of epidermal growth factor receptor (EGFR) and Kirsten rat sarcoma viral oncogene (KRAS) mutations in lung adenocarcinoma has become an integral part of lung cancer diagnosis and treatment; however, their prevalence varies with ethnicity. Little is know concerning their prevalence in Arab populations. In the present study, mutational analysis for EGFR and KRAS was performed on two cohorts of the Lebanese population. Lung adenocarcinoma cases (106) underwent mutational analysis for KRAS in exon 2, codon 12 and 13 and exon 3 codon 61 by reverse hybridization using the KRAS 12/13/61 StripAssay®. Subsequently, cases with no KRAS mutations underwent EGFR mutational analysis using the EGFR RGQ polymerase chain reaction (PCR) kits for real‑time PCR on the Rotor‑Gene Q 5-plex HRM. KRAS mutations were detected in 37.7% of 106 lung adenocarcinomas; 85% had a G>T substitution in codon 12 and 13 of exon 2, and 8.5% had EGFR mutations with exon 19 deletions (88.9%) and one case with L858R substitution in exon 21. EGFR mutations were significantly correlated with females, non-smokers and well differentiation of the tumor. This is the first study in an Arab population that reports the prevalence of both EGFR and KRAS gene mutations in lung adenocarcinoma using very sensitive mutational analysis techniques. Therefore, EGFR reflex testing should be implemented in the management of lung adenocarcinomas, while KRAS testing must await the identification of effective targeted therapy.