Clinicopathologic and genomic features of high-grade pattern and their subclasses in lung adenocarcinoma. (August 2022)

• Record Type: Journal Article
• Authors: Ahn, Bokyung; Yoon, Shinkyo; Kim, Deokhoon; Chun, Sung-Min; Lee, Goeun; Kim, Hyeong-Ryul; Jin Jang, Se; Sang Hwang, Hee
• Is Part Of: Lung cancer. Volume 170(2022)
• Page Start: 176
• Page End: 184
• Publication Date: 2022-08
• Subjects: Lung adenocarcinoma -- Histologic grading -- Next-generation sequencing -- TP53 gene -- Cell cycle-related genes; Lungs -- Cancer -- Periodicals; Lung Neoplasms -- Abstracts; Lung Neoplasms -- Periodicals; Poumons -- Cancer -- Périodiques; Lungs -- Cancer; Periodicals; Electronic journals; Electronic journals; 616.99424
• DOI: 10.1016/j.lungcan.2022.07.003
• Languages: English
• ISSNs: 0169-5002

Abstract

Highlights: Clinicopathologic features and survival of IASLC grade 3 LUAD are not uniform. Stratification of IASLC grade 3 LUAD by high-grade pattern reveals distinct subgroup. TP53 and RB1 alterations in LUAD predict poor survival outcome. Abstract: Introduction: Recent lung adenocarcinoma (LUAD) grading system proposed by the International Association for the Study of Lung Cancer (IASLC) has emphasized the proportion of high-grade patterns (HGPs). We aimed to evaluate the clinicopathologic and genomic characteristics associated with HGP which has not yet been fully investigated. Methods: Tissue samples from 174 patients who underwent surgical resection of LUAD from January to December 2015 were histologically evaluated. Proportions of HGPs, including solid, micropapillary, cribriform, and complex glandular patterns, were individually quantified. Prognostic implications of HGP proportion, both as a continuous variable and as subclasses divided by cutoffs of 20%, 50%, and 90% (low-intermediate grade [LIG], HGP <20%; high grade 1 [HG1], 20-<50%, HG2, 50-<90%; HG3, ≥90%) were evaluated. Different clinicopathologic factors and genomic alterations according to the HGP subclasses were assessed. Results: Relative hazards of the HGP gradually elevated as its proportion increased over 20%, the cut-off value established by the IASLC grading system, and the cancer-specific overall survival (OS) of HG1 subclass was not significantly decreased compared to the LIG subclass on univariate analysis. However, further subgrouping showed significantly increased frequencies of male, advanced stage tumors, lymphovascular invasion, and spread through alveolar space in higher HGP subclasses. Also, common LUAD driver mutations, particularly EGFR mutations, were less frequent, whereas alterations in TP53 and cell cycle pathway-related genes were more frequent. Higher HGP subclasses and TP53 gene alteration were associated with shorter cancer-specific OS and RFS in multivariate survival analysis. Conclusions: HGP subclasses of LUAD displayed distinct clinicopathological characteristics and genomic alterations, including TP53 and cell cycle pathway, emphasizing the clinical value of these subclasses in LUAD. Higher HGP subclass and alteration in TP53 may be markers of poor post-operative survival.