Epidermal growth factor receptor mutations in Lebanese non-small cell lung cancer patients

Non Small Cell Lung Cancer (NSCLC) is the major subtype of lung cancers (85%) which is the leading cause of cancer related deaths worldwide. Advances in personalized medicine and in our understanding of the tumor biology along with the identification of special molecular alterations have allowed the development of new treatment approaches for NSCLC, thus providing a marginal improvement in responses and overall survival (OS). Small tyrosine kinase inhibitors (TKIs), which target the tyrosine kinase intracellular domain of the epidermal growth factor receptor (EGFR), have had a remarkable efficacy in treating NSCLC but the responses varied between the patients. This variation is due to the EGFR mutational status. In normal cells, epidermal growth factors (EGF) bind to EGFR and activate several signal transduction pathways which regulate cell differentiation, proliferation, migration, survival, angiogenesis, and apoptosis. In NSCLC, EGFR can be altered either by over-expression or by different mutations. The mutations can occur in exons 18,19,20,21. Clinical studies have shown that if the patient harbors the EGFR mutation, the progression free survival (PFS) is higher than the one with a wild type gene when treated with TKIs. The aim of this diploma work is to perform, an epidemiologic study to determine the prevalence of EGFR mutations in Lebanese NSCLC patients and its correlation with the patient's gender. To process this study, we've analyzed the data provided by the Lebanese National institute of pathology (INP). These data consisted of reports revealing EGFR mutational status in addition to patients personal information of 180 formalin fixed paraffin embedded NSCLC tumor tissues (FFPET). Statistical tests have shown that the EGFR mutations occur in 13.3% of the NSCLC cases in Lebanon, which means that only 13.3% of the patients benefit from the TKI therapy. We've also found that there is no significant correlation between the EGFR mutational status and the patient's gender, and the highest mutational rate was detected in exon 19 (75%), followed by exon 21 (21%).