Abstract
BackgroundTumor spread through air spaces (STAS) is a novel pathologic characteristic in lung adenocarcinomas that indicates invasive tumor behavior. We aimed to explore the relationship between Twist, Slug and STAS in lung adenocarcinoma and to investigate the potential relationship between epithelial‐mesenchymal transition (EMT) and STAS.Materials and methodsOur study retrospectively analyzed 115 patients with resected lung adenocarcinomas to evaluate the relationship between Twist, Slug and STAS. STAS was diagnosed using hematoxylin‐eosin (H&E) staining. Immunohistochemistry was used to evaluate the expression levels of Slug and Twist.ResultsIn this study, 56 (48.7%) patients had STAS, 40 (34.8%) patients had Slug overexpression, and 28 (24.3%) patients had Twist overexpression. Patients with either STAS or Slug and Twist overexpression experienced poor recurrence‐free survival (RFS) and overall survival (OS). There were significant associations between Twist overexpression, Slug overexpression and the presence of STAS. The logistic model further revealed that pathological stage, Twist overexpression and Slug overexpression were independent risk factors for STAS. A multivariate analysis that contained Twist, Slug, pathologic stage and STAS, showed that pathologic stage and STAS were independent prognostic factors for poor RFS and OS. Another multivariate model that contained Twist, Slug and pathologic stage, showed that pathologic stage, Twist overexpression and Slug overexpression were independent risk factors for poor RFS and OS. In the cohort with STAS, the multivariate analysis showed that pathologic stage and Twist overexpression were independent risk factors for poor survival. The subgroup analysis showed that patients with both Slug overexpression and Twist overexpression with STAS received a poor prognosis.ConclusionsSTAS, Slug and Twist were correlated with poor RFS and OS in resected lung adenocarcinomas. Additionally, STAS was correlated with the overexpression of Twist and Slug, which could potentially provide information on the mechanism of STAS.
Highlights
Spread through air spaces (STAS) is a new pathologic feature of tumor invasion.[1]
One multivariate analysis including pathologic stage, spread through air spaces (STAS), Twist and Slug showed that pathologic stage (HR, 1.783; 95% confidence interval (CI), 1.313-2.421; P < .001) and the presence of STAS (HR, 2.638; 95% CI, 1.464-4.754; P = .001) were independent prognostic risk factors for poor recurrence-free survival (RFS)
We found that Twist and Slug overexpression was associated with decreased RFS and overall survival (OS) in patients with lung adenocarcinoma according to the survival analysis
Summary
It has been reported that cancer cells beyond the edge of the tumor invaded into the alveolar spaces in the lung surrounding parenchyma shown as single cells, micropapillary patterns or solid nests.[2]. It was reported that metastasis-associated protein 1 (MTA1) might provide potential information on the mechanism of STAS.[11]. The adhesion protein E-cadherin is one of the hallmarks of epithelial morphogenesis. The decreased expression of cell adhesion molecules, such as E-cadherin, is one of the main characteristics in the activation of epithelial-mesenchymal transition (EMT). In EMT, polarized epithelial cells lose their epithelial characteristics, intercellular adhesion complexes and cytoskeletal-specific architecture, and convert into a motile mesenchymal type of cell with polarity, invasive ability and metastatic capacity.[12-14]. E-cadherin expression is downregulated during the acquisition of metastatic potential at the later stages of epithelial tumor progression.[15,16].
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