117P Classification of EGFR mutations in Pakistani lung adenocarcinoma for predicting response to targeted therapy

Abstract

Lung cancer is the 4th leading cause of death in all cancers. Adenocarcinomas of lung constitute up to 50% of NSCLC. In Pakistan like rest of the world lung cancer prevalence is high (15%) and primary lung adenocarcinoma constitute about 40–45% of primary lung cancer. Mutations in EGFR tyrosine kinase domain have been reported in adenocarcinoma. EGFR mutation screening has become imperative for the selection of metastatic NSCLC patients eligible for targeted treatment. This report presents distribution of EGFR mutations in 315 NSCLC patients. EGFR mutation in tumor samples was screened by multiplex real time PCR (Roche Diagnostics(R), USA) according to the manufacturer's instructions. Briefly, DNA from FFPE tissue, obtained from Histopathology sections, was extracted and amplified with primers and probes specific to 43 different EGFR mutations in Cobas z 480 instrument. The assay can detect 43 mutations in four exons (18–21) of EGFR gene, including several point mutations, deletions and insertions. Out of 315 patients, 208 were male and 107 were females; male to female ratio was 2:1. The mean age of the patients was 62 years and age distribution was 23 and 85 years. On the basis of immuno histopathological finding tumors were categorized into two groups; well to poorly differentiated adenocarcinoma 231(73%) and metastatic adenocarcinoma 84 (27%). EGFR mutation Del 19 was detected in 38 patients, its short in-frame deletion in exon 19, clustered around the amino acid resideus747–750(most common variant delL746-A750, delL747-T751insS, and delL747-P753insS). Whereas L858R point mutation (substitution of amino acid leucine to arginine) was found in 27 patients. In two patients compound mutation, two point mutations together [S768I and G719X] and another one insertion (amino acid residues inserted) on Exon 20 was observed. L858R (exon 21) and deletion 19 exon were most frequent mutations in primary lung adenocarcinoma patients of Pakistani origin, in published literature female preponderance was significant. Our study showed Del 19 and L858R were the most frequent mutations in Pakistani lung cancer patients. In additions, 25% of the patients were found eligible for targeted therapy.