P2.09-01 Characteristics of Driver Mutations in Early Lung Adenocarcinoma: From Preinvasive/Minimally invasive to Invasive Adenocarcinoma

Abstract

It is still unclear when the gene mutation occurs during the carcinogenetic process, which progresses from preinvasive to invasive adenocarcinoma. We aim to investigate the driver gene alterations profile of adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA) and invasive adenocarcinoma (IAC). A total of 1219 patients with pulmonary nodes smaller than 3 cm were selected for this study. Driver mutation testing was performed with NGS in all resected tumor tissues. The incidence of mutations was calculated and compared among different subtypes. Logistic regression was used to further identify factors that may independently correlate with IAC. In all 1219 patients with lung adenocarcinoma, 62 were diagnosed as AIS, 208 as MIA and 949 as IAC. Mutations were found in 809 (66.4%) patients. The frequency of mutations increased with the progression of tumor invasiveness: AIS (32.3%), MIA (45.2%) and IAC (73.2%)(P<0.001 between IAC and AIS, P<0.001 between IAC and MIA). The results (Figure 1) also showed an increasing trend towards more driver mutations from AIS to MIA, and to IAC. Multivariate analysis revealed that driver mutations was a factor associated with IAC (OR: 2.39, P<0.001). Of the genetic factors, EGFR, KRAS and ALK alterations were significant indicators of IAC (all P<0.020), and were found increased in IAC compared with AIS/MIA. Genetic alterations occurs early in the development of lung adenocarcinoma and can be detected even before tumor have acquired malignant potential. Driver mutations gradually increase in tumorigenesis and progression from AIS to MIA, and finally to overt IAC. A better understanding of carcinogenesis in preinvasive/minimally invasive cases may allow the development of effective preventive, screening, and treatment strategies.