Abstract 3680: Comparative mutational evaluation for multiple lung cancer by multiplex oncogene mutation analysis

Abstract

Abstract [Background] In the treatment of synchronous or metachronous multiple lung cancer (MLC), determination whether multiple primary lung cancer (MP) or intrapulmonary metastases (IM) is very important to make an appropriate management. Clinical or pathological diagnoses have been adopted to distinguish whether MLC were MP or IM, however, the accuracy of these approaches seemed to be insufficient. On the other hand, recent evolution of high-throughput sequencing made it possible to perform comprehensive gene mutation analysis in cancer cells. The aims of this study were to investigate mutational profiles of synchronous or metachronous MLC, and to compare multiplex gene mutation analysis of MP or IM among paired tumors with clinical or pathological evaluations. [Methods] We performed targeted sequencing for 20 lung cancer related oncogenes using next-generation sequencing technology in 82 tumors from 37 patients (18 patients with synchronous MLC and 19 patients with metachronous MLC) who underwent surgical resection in our department from July 2002 to April 2013. Then, classification of MP or IM was made by clinical, pathological, and gene mutational evaluation. [Results] Among paired tumors, matching of mutation was observed in 20 (54%) cases (nine cases with completely matched and 11 cases with partially matched), which were diagnosed as IM by mutational evaluation. In pathologically suggested IM cases (n=7), six (86%) patients were interpreted as IM by mutational evaluation, and most of them (n=5) had multiple matched mutations, which suggested the clonality between paired tumors strongly. In pathologically suggested MP cases (n=17), the mutational diagnosis was discordant in eight (47%) patients. Among these cases, four paired tumors had multiple matched mutation, suggesting the pathological diagnosis in these cases might be incorrect. In addition, careful interpretation was required when the paired tumors harboring frequent mutation including TP53 or EGFR because such mutation may match accidentally. [Conclusion] Our findings suggest that multiplex mutational analysis of synchronous or metachronous MLC could complement the pathological diagnosis in differentiation whether MP or IM. In the cases with pathologically equivocal or those with discordant between pathological diagnosis and mutational evaluation, the frequency and the number of matched mutation may be helpful for the differentiation. Citation Format: Yuta Takahashi, Kazuhiko Shien, Shuta Tomida, Eisuke Kurihara, Yusuke Ogoshi, Kei Namba, Takahiro Yoshioka, Hidejiro Trigoe, Hiroki Sato, Hiromasa Yamamoto, Junichi Soh, Shinichi Toyooka. Comparative mutational evaluation for multiple lung cancer by multiplex oncogene mutation analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3680.