P2.03b-021 Screening for Major Oncogene Alterations in Adenosquamous Lung Carcinoma Using PCR Coupled with Next-Generation and Sanger Sequencing Methods: Topic: Biomarkers

Abstract

Despite progress in personalized lung adenocarcinoma treatment, development of efficacious molecular targeted therapies for adenosquamous cell carcinoma (ASC) of the lung has made little progress because of limited knowledge concerning gene mutation status and the rarity of this type of tumor. We examined the frequency of EGFR, K-Ras, B-Raf, PIK3CA, DDR2, ALK, and PDGFRA gene mutation using NGS, PCR, and Sanger sequencing methods in ASC samples. Macrodissection or laser microdissection was performed in 37 cases to separate adenomatous and squamous components of ASC for further sequencing. Fifty-six patients who underwent operations in Peking Union Medical College Hospital between January 2010 and December 2014 were enrolled in the study. The overall mutation rate was 64.29%, including 55.36%, 7.14%, and 1.79% for EGFR, K-Ras, and B-Raf mutations, respectively. PIK3CA mutation was detected in three cases; all involved coexisting EGFR mutations. Of the 37 cases, 34 were convergent in two components, while three showed EGFR mutations in the glandular components and three showed PIK3CA mutations in the squamous components. With respect to EGFR mutations, the number of young female patients, nonsmokers, and those with positive pleural invasion was higher in the mutation-positive group than that in the mutation-negative. K-Ras mutation was significantly associated with smoking. Overall survival in the different EGFR mutation groups differed significantly. The frequency and clinicopathological characteristics of EGFR- and KRAS-mutated adenosquamous lung carcinoma were similar to that noted in Asian adenocarcinomas patients. The high convergence mutation rate in both adenomatous and squamous components suggests monoclonality in ASC.