MA14.05 Clinicopathologic and Genomic Significances of the Amount of High-Grade Histologic Components in Lung Adenocarcinoma

Abstract

Recent proposal of grading system for lung adenocarcinoma (LUAD) from the pathology committee of International Association for the Study of Lung Cancer emphasizes the amount of high-grade components (HGC) in the prognostic stratification of LUAD. Underlying pathobiologic features supporting the biologic significance of HGC in LUAD has not been fully evaluated yet. A total of 175 cases of surgically resected LUAD from January to December 2015 in Asan Medical Center were histologically evaluated. Proportions of HGCs, including solid, micropapillary, and cribriform patterns, were individually quantified, and cases were classified by the cutoff of 1, 5, and 20% according to the summated proportion of HGCs. Genomic features including the mutational profile, fraction of genome altered (FGA), and tumor mutation burden (TMB), were analyzed from the correspondent targeted next generation sequencing dataset and correlated with the HGC class. About 14% (25/175), 27% (47/175) and 30% of the cases (52/175) had 1-<5%, 5-<20% and ≥20% of HGCs, respectively (Figure 1A). Frequencies of lymphovascular invasion was proportionally elevated when the HGCs components were elevated (P<0.0001). Remarkably, >90% of the cases harboring ≥1% of HGCs had spread-through alveolar space (STAS) (P<0.0001). The pathological stage was also elevated in all three groups with HGCs (P<0.0001) (Figure 1B). Comparison of the mutational profile revealed that the rates of EGFR mutation were significantly diminished in HGC ≥20% group only, but TP53 mutation rates were proportionally elevated when the HGCs were elevated (P = 0.001) (Figure 1C). Furthermore, FGA and TMB rates were elevated in all three groups with HGC ≥1% (FGA, P = 0.001; TMB, P<0.0001) (Figure 1D). On univariate survival analysis, both groups with HGC 5-<20% and ≥20% showed significantly inferior overall and recurrence-free survivals with similar survival lengths; HGC 1-<5% groups showed intermediate prognosis (Figure 1E). On multivariate survival analyses, HGC 5-<20% and ≥20% groups were independently associated with poor OS, but only HGC 5-<20% group was statistically significant in comparison with RFS. The clinicopathological characteristics and genomic alterations were significantly different even when ≥1% of the HGCs were accompanied in LUAD. Furthermore, both groups with 5-<20% and ≥20% of HGCs correlated with inferior survival outcomes with similar level, which implicates the clinicopathologic and genomic significance of minor HGCs in LUAD.