P1.02-012 Frequencies of Actionable Mutations and Survival in Variants of Invasive Adenocarcinoma of the Lung

Abstract

2015 new WHO classification lists four rare variants of invasive adenocarcinoma of the lung (VIA): invasive mucinous adenocarcinoma, colloid adenocarcinoma, fetal adenocarcinoma and enteric adenocarcinoma. Very little information is known regarding the molecular alterations and prognostic values for rarity of VIA. The aim of present study was to investigate the common actionable mutations and survival in VIA. Patients who with pathologic confirmed as VIA with completely resected stage I-IIIA were enrolled from 2010 to 2013. For comparison, we evaluated the gene status and survival from 380 non-VIA lung adenocarcinoma patients in 2012. RT-PCR was utilized for detecting the mutations of EGFR, KRAS, NRAS, PIK3CA, BRAF, HER2 and the fusion of ALK, ROS1 and RET. Survival curves were plotted with Kaplan-Meier method. Thirty one patients were recruited from 1120 lung adenocarcinoma, including invasive mucinous adenocarcinoma (n=15), enteric adenocarcinoma(n=9), colloid adenocarcinoma (n=4) and fetal adenocarcinoma(n=3) . The overall frequency of gene abnormality in VIA was 48.4% (15/31). The genes abnormality was as follows: KRAS mutation (n=5), ALK rearrangement (n=4),PIK3CA (n=2), EGFR mutation (n=2), HER2 mutation (n=1) and ROS1 rearrangement (n=1). No mutations of NRAS, BRAF or RET were observed. The frequency of gene abnormality was lower in VIA than non-VIA patients (48.4% vs.74.7%, P=0.0015). No recurrence free survival difference existed in the VIA and non-VIA patients (38.0 vs.47.0 months, P=0.524). A trend of worse overall survival in VIA than those with non-VIA patients was found (48.0vs.57.0 months, P=0.052). VIA is rare in lung adenocarcinoma with lower frequency of common gene abnormality. Invasive mucinous adenocarcinoma was the most frequent subtype and KRAS was a predominant actionable mutation in VIA patients. A trend of worse survival existed in VIA than non-VIA patients.