Genetic and clinicopathologic characteristics of lung adenocarcinoma with tumor spread through air spaces

Abstract

ObjectiveThe World Health Organization Classification of Lung Tumors considers “Spread Through Air Spaces (STAS)” as a form of invasion in lung adenocarcinoma. However, its existence as an independent pathologic entity rather than an artifact caused by spreading through a knife surface is still controversial. Therefore, we performed comprehensive analyses on the genetic and clinicopathologic characteristics of lung adenocarcinoma with STAS. Materials and MethodsA total of 316 surgically resected lung adenocarcinoma cases were analyzed retrospectively. Detailed analyses were performed on clinical-histological-molecular features. Tumor STAS was defined as tumor cells within air spaces in the lung parenchyma beyond the edge of the main tumor. ResultsSTAS was observed in 160 cases (50.6%). STAS was significantly related to lymphovascular invasion, lymph node metastasis, higher stage, and high-grade histologic subtype. STAS was frequently found in tumors with wild-type EGFR or ALK-rearrangement. Logistic regression analysis showed that STAS was significantly associated with absence of lepidic component, presence of micropapillary component, cribriform predominant type, lymphovascular invasion, and wild-type EGFR. Multivariate survival analysis demonstrated that STAS was independently associated with shorter recurrence-free survival. STAS was also associated with recurrences to extrathoracic sites as well as intrathoracic sites. ConclusionSTAS is associated with certain pathological and molecular subtypes. STAS might be a parameter for tumor aggressiveness in that it is strongly associated with poor prognostic factors and recurrence, including to extrathoracic sites.