Comprehensive Investigation of Mutational Features of Various Lung Adenocarcinoma Histological Subtypes among Chinese Patients.

e21090 Background: Lung adenocarcinoma (LUAD) is further classified into several histological subtypes according to the World Health Organization classification; however, data on the molecular profile of these histological subtypes are limited. In this study, we aimed to investigate the mutational features of various LUAD histological subtypes among Chinese patients. Methods: We retrospectively analyzed clinical, histopathologic, and sequencing data from 3,425 consecutive patients diagnosed with stage IA-IVB LUAD between January 2017 to December 2019 at the Department of Pathology. Results: Based on histologic subtype, the cohort comprised of 0.2% atypical adenomatous hyperplasia (AAH, n = 6), 7.2% adenocarcinoma in situ (AIS, n = 246), 14.0% minimally invasive adenocarcinoma (MIA, n = 479), and 78.6% invasive adenocarcinoma (INV, n = 2,694), including 42.0% acinar (n = 1,438), 12.7% papillary (n = 435), 8.8% lepidic (n = 302), 8.5% solid (n = 290), 3.2% micropapillary (n = 109), 2.8% invasive mucinous (n = 95), 0.6% enteric (n = 21), 0.1% fetal (n = 3), and 0.1% colloid (n = 1). Analysis of mutation profiles revealed significantly higher mutation detection rates of ERBB2 ( P< 0.01), BRAF ( P< 0.01), and MAP2K1 ( P= < 0.01) among patients with AIS, AAH and MIA as compared to patients with INV. Meanwhile, TP53 ( P< 0.01) and EGFR ( P< 0.01) mutations were significantly higher among patients with INV as compared to patients with AIS and MIA. Among the invasive subtypes, patients with invasive mucinous adenocarcinoma had significantly higher KRAS mutation rate (75%, P< 0.01). Lepidic (81%), acinar (80%), papillary (77%), and micropapillary (66%) were the subtypes with the highest EGFR mutation rates. Conclusions: By analyzing the genomic data of a large cohort of patients, our study provides a more comprehensive outlook of gene mutations according to LUAD histological subtypes. Enrichement of actionable mutation in particular histological subtype contributes to more treatment option and better clinical outcomes as compared to other histological subtype, indicating the clinical relevance of performing comprehensive mutation profiling in addition to histopathologic analysis in all LUAD patients.