Abstract 3149: Genetic alteration of lung adenocarcinomas with micropapillary component.

Abstract

Abstract Purpose: Adenocarcinoma with micropapillary component (AMPC) is known as one of aggressive subtypes among lung adenocarcinoma. The molecular profiles of AMPC have not been well characterized from the view point of difference from other adenocarcinomas. In this study, we analyzed molecular alterations of AMPC to investigate its molecular pathogenesis. Methods: We reviewed pathological reports of patients who underwent surgical resection for lung cancers between April 2004 and May 2012. Twenty-eight patients were recorded to possess micropapillary component among 674 patients diagnosed as lung adenocarcinoma. A total of 52 resected lung adenocarcinomas without micropapillary component were selected in the same period so as to adjust age, sex, and smoking status to those of the patients with micropapillary component. Mutational status was determined by the following two methods: SNaPshot assay based on multiplex PCR, primer extension, and capillary electrophoresis that was designed to assess for 38 somatic mutations in eight genes (AKT1, BRAF, EGFR, KRAS, MEK1, NRAS, PIK3CA, and PTEN), and a PCR-based sizing assay that assesses for EGFR exon 19 deletions, EGFR exon 20 insertions, and HER2 exon 20 insertions. EML4-ALK fusion was screened by ALK immunohistochemistry and confirmed using reverse transcriptional PCR assay and break-apart FISH assay.Results: As for genetic alterations, 13 (46.4%) of 28 lung adenocarcinomas with micropapillary component harbored mutually exclusive mutations: 9 (32.1%) EGFR mutation, 1 (3.3%) KRAS mutation and 3 (9.9%) EML4-ALK fusion. Adenocarcinomas without micropapillary component harbored 11 (21.2%) EGFR mutations and 8 (15.3%) KRAS mutations in a mutually exclusive manner, but had no EML4-ALK fusion genes. There were no mutations in AKT1, BRAF, EGFR, KRAS, MEK1, NRAS, PIK3CA, PTEN and HER2 genes in the both groups. EML4-ALK fusions appeared to occur significantly more frequent in AMPC than in control cases (P = 0.039).Conclusion: Although the size of our study was small, our study suggests the molecular pathogenesis of AMPC may be different from other adenocarcinoma, associated with its unique character among lung adenocarcinomas. Citation Format: Masashi Furukawa, Shinichi Toyooka, Hiromasa Yamamoto, Ryuhei Tada, Shinsuke Hashida, Kazuhiko Shien, Junichi Soh, Hiroaki Asano, Kazunori Tsukuda, Mamoru Ouchida, Kouichi Ichimura, Shinichiro Miyoshi. Genetic alteration of lung adenocarcinomas with micropapillary component. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3149. doi:10.1158/1538-7445.AM2013-3149