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Updated: Sep 13, 2025
Next Generation Sequencing for the Detection of Actionable Mutations in Solid and Liquid Tumors
Published on: September 20, 2016
HER2 mutations in pulmonary adenocarcinoma presenting with ground-glass nodules
Jiacheng Yin1, Shuhua Huo2, Zhencong Chen1
1Department of Thoracic Surgery, Zhongshan Hospital of Fudan University, No. 180, Fenglin Road, Shanghai, 200032, China.
Background:
Human epidermal growth factor receptor 2 (HER2) mutations have been identified as oncogenic drivers and therapeutic targets in Non-small cell lung cancers (NSCLCs). The role of HER2 mutation in lung adenocarcinoma presented as sub-solid nodules (SSNs) have not been distinctly defined. This study comprehensively investigated the clinicopathological characteristics of HER2 mutation in patients with pulmonary SSNs.
Methods:
In total, 717 patients with completely resected NSCLCs presented as SSNs were examined for HER2 mutation from January 2016 to December 2018. Age, sex, smoking history, radiologic features, operative procedure, pleural invasion, histologic subtypes and tumor-node-metastasis stage were collected. Kaplan-Meier method was used to estimate DFS, Log-rank test was used to compare the survival data. Logistic regression model was used to identify the predictors for HER2 mutation and the predictive nomogram was built.
Results:
In this study, 47(6.6%) SSNs carried HER2 mutations. HER2 mutations were more frequent in subjects with younger age (P < 0.001) and smaller tumor size (P < 0.001), and were prone to occur in AIS and MIA (P < 0.001). The 5- year DFS rates for HER2 mutation and HER2 wild-type groups were similar (P = 0.509). According to the logistic regression analysis, age and maximum tumor size were independent variables correlated with HER2 mutation. A predictive nomogram model was constructed with a concordance statistic of 0.79 (0.71-0.87).
Conclusions:
HER2 mutation was not uncommon in pulmonary SSNs. Younger age and smaller tumor size were associated with increased odds of HER2 mutation.
Insights
Human epidermal growth factor receptor 2 (HER2) mutations are present in lung adenocarcinomas manifesting as sub-solid nodules (SSNs). Younger age and smaller tumor size are linked to higher odds of HER2 mutation in these SSNs.
Area of Science:
- Oncology
- Genetics
- Pulmonology
Background:
- Human epidermal growth factor receptor 2 (HER2) mutations are recognized oncogenic drivers and therapeutic targets in Non-small cell lung cancers (NSCLCs).
- The specific role of HER2 mutations in lung adenocarcinomas presenting as sub-solid nodules (SSNs) remains incompletely defined.
- This study aimed to comprehensively investigate the clinicopathological characteristics of HER2 mutations in patients with pulmonary SSNs.
Purpose of the Study:
- To investigate the clinicopathological characteristics of HER2 mutations in patients with pulmonary SSNs.
- To identify predictors of HER2 mutation in SSNs.
- To assess the clinical significance of HER2 mutations in SSNs.
Main Methods:
- Examined 717 patients with completely resected NSCLCs presenting as SSNs for HER2 mutations.
- Collected data on age, sex, smoking history, radiologic features, operative procedure, pleural invasion, histologic subtypes, and tumor-node-metastasis stage.
- Employed Kaplan-Meier method for DFS estimation, Log-rank test for survival comparison, and logistic regression for predictor identification, constructing a predictive nomogram.
Main Results:
- HER2 mutations were identified in 47 (6.6%) SSNs.
- HER2 mutations were more frequent in younger patients and smaller tumors, and common in Adenocarcinoma in situ (AIS) and Minimally invasive adenocarcinoma (MIA).
- Five-year disease-free survival (DFS) rates were similar between HER2 mutation and wild-type groups. Age and maximum tumor size were independent predictors of HER2 mutation, with a predictive nomogram achieving a concordance statistic of 0.79.
Conclusions:
- HER2 mutations are not uncommon in pulmonary SSNs.
- Younger age and smaller tumor size are associated with an increased likelihood of HER2 mutation in SSNs.
- The findings contribute to understanding the molecular landscape of SSNs and may inform future targeted therapies.
