Assessment of intratumoral heterogeneity of oncogenic driver mutations in surgically-resected lung adenocarcinoma: implications of percutaneous biopsy-based molecular assay for target-directed therapy.

AIM: The present study investigated whether there is intratumoral heterogeneity of oncogenic driver mutations within surgically-resected tumors and between surgical specimens and percutaneous biopsy samples. PATIENTS AND METHODS: Thirty-four patients who underwent surgery for lung adenocarcinoma were studied. We obtained four to five snap-frozen samples from each surgical specimen. Mutational analyses of epidermal growth factor receptor (EGFR), Kirsten rat sarcoma viral homolog (KRAS), v-raf murine sarcoma viral oncogene homolog B (BRAF), and phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit-alpha (PIK3CA) genes were performed and then compared in multiple surgical specimens and between surgical and percutaneous biopsy samples. RESULTS: EGFR and KRAS mutations were detected in 19 and 2 patients, respectively. Multiple surgical samples from different areas of the tumor had the same mutation genotype in all cases except for one. The 14 biopsy specimens had the same mutational profiles as the corresponding surgical specimens. CONCLUSION: Heterogeneous distributions of oncogenic driver mutations were not found in surgically-resected lung adenocarcinoma. Small tumor specimens obtained with percutaneous biopsy were suitable for EGFR analyses, thus providing critical information for personalized therapy.