Evolution of lung adenocarcinoma from preneoplasia to invasive adenocarcinoma

Abstract

Objective: Mutations in driver genes contribute to the development and progression of lung adenocarcinoma (LUAD). However, in the dynamic evolutionary process from adenocarcinoma in situ (AIS) to minimally invasive adenocarcinoma (MIA) and eventually to invasive adenocarcinoma (IAC), the role of driver genes is currently unclear. This study aimed to analyse the role of driver gene status in the progression of LUAD from preneoplasia to IAC.Methods: Patients with LUAD who underwent surgery in our centre from March 2015 to December 2019 were retrospectively analysed, and LUAD patients with tumour sizes ≤3.0 cm and pN0 were included in the final analysis. The mutation status of common driver genes, including EGFR, ALK and ROS1, was detected.According to the pathological characteristics, the patients were divided into three stages: AIS, MIA and IAC. We analysed the distribution of driver gene mutation frequencies across three stages of LUAD. In addition, we performed univariate and multivariate analyses of IAC patients to screen for relevant variables (driver genes and clinicopathological features) affecting their prognosis.

Molecular pathology of non‐small cell carcinoma

“…In our analysis of 1365 lung cancers, 240 adenocarcinomas with an invasion size of ≤ 1 cm exhibited comparable frequencies in the entire cohort (Figure 4). This finding was supported by a recent comprehensive analysis and the driver alteration prevalence was comparable among adenocarcinoma in situ , minimally invasive adenocarcinoma and invasive adenocarcinomas 72,120–122 . Once driver alterations are acquired, progression becomes reportedly associated with copy number gain or gene amplification.…”

“…This finding was supported by a recent comprehensive analysis and the driver alteration prevalence was comparable among adenocarcinoma in situ, minimally invasive adenocarcinoma and invasive adenocarcinomas. 72,[120][121][122] Once driver alterations are acquired, progression becomes reportedly associated with copy number gain or gene amplification. EGFR-mutated tumours frequently display heterogeneously distributed EGFR amplification that is selectively involved in invasive or high-gradeareas, suggesting an association between amplification and tumour progression to invasive adenocarcinoma.…”

The predictive value of computed tomography value on high-resolution images in differentiating invasive from indolent lung adenocarcinoma

“…Adenocarcinoma is the most common pathological subtype of lung cancer and is generally considered to develop via tumorigenesis and progression from AAH to AIS, MIA, and ultimately to IA with a lepidic pattern ( 10 ). During this progressive process, tumor tissue components increase, alveolar septa thicken, and air spaces decrease, which can be shown as an increase in size and density on CT images ( 11 ).…”

Progress in the treatment of lung adenocarcinoma by integrated traditional Chinese and Western medicine

“…Lung cancer stands as the predominant malignant ailment in China, with a staggering annual incidence of 789,000 new cases and approximately 631 deaths ( 1 ). Non-small cell lung cancer, chiefly represented by lung adenocarcinoma, encompasses a spectrum of clinicopathological types, including invasive adenocarcinoma (IAC), invasive adenocarcinoma variants, micro-invasive adenocarcinoma (MIA), and pre-infiltrative lesions; the latter category further bifurcates into adenocarcinoma in situ (AIS) and Atypical adenoma hyperplasia (AAH) ( 2 ). Notably, early-stage lung adenocarcinoma patients typically remain asymptomatic and are often incidentally diagnosed during routine physical examinations.…”

“…However, the highly infiltrative and metastatic nature of lung adenocarcinoma occasionally results in distant metastases upon diagnosis. Patients in the intermediate and advanced stages of the disease frequently manifest conspicuous symptoms, primarily characterized by hemoptysis, chest tightness, dyspnea, and bone pain, among others ( 2 ).The therapeutic management of lung adenocarcinoma in Western medicine varies based on disease staging. In the early stages, surgical resection assumes a pivotal role, achieving a curative effect through tumor excision.…”