Abstract 2124: The analysis of EGFR genetic heterogeneity on mixed adenocarcinoma of the lung

Abstract

Abstract Background: The epidermal growth factor receptor thyrosine kinase inhibitors (EGFR-TKIs) are effective for non-small cell lung cancer (NSCLC) patients harboring sensitive EGFR mutations. However, every patient eventually relapse even if the treatment of EGFR-TKIs was effective remarkably. It have been reported a secondary T790M mutation, MET amplification and some mechanisms attribute to the drug resistance. Intratumor EGFR genetic heterogeneity has also been considered as a potential cause of the acquired resistance. We previously reported a patient with mixed adenocarcinoma of the lung that had different EGFR mutations in papillary, acinar and BAC subtypes. In this study, we analyzed EGFR mutations in each histological subtypes of mixed adenocarcinoma after surgery and pre EGFR-TKIs treatment. Material and Methods: We recruited twelve mixed adenocarcinoma patients who were treated surgical therapy. Tumor cells in different histological subtypes were microdissected from paraffin-embedded surgical specimens with AS LMD system. Genomic DNA was extracted from each sampled area. EGFR mutations, limited to exon19 deletions and L858R mutations, were examined using the simple polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism (RFLP) methods. Results: Acinar, BAC and papillary sanmples were microdissected from six, ten and eleven tumor tissues. Exon19 deletions and L858R mutation were detected in five and one tissues. From acinar, BAC and papillary samples, one exon19 deletion, two exon19 deletions and three exon19 delitions and one L858R were detected. Out of the six mixed adenocarcinoma, five tissues consisted both mutated and non-mutated cells. Conclusions: Our results indicates that 41% of lung adenocarcinoma with mixed subtypes have intratoumor genetic heterogeneity. EGFR mutations were detected most frequently in papillary samples. There may be some relations between histological subtype and EGFR mutation. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2124.