Department of General Thoracic Surgery, Faculty of Medicine, Kagawa University, 1750-1, Ikenobe, Miki-cho, Kagawa, 761-0793, Japan.
Department of Diagnostic Pathology, Faculty of Medicine, Kagawa University, 1750-1, Ikenobe, Miki-cho, Kagawa 761-0793, Japan.
Lung Cancer. 2021 Mar;153:49-55. doi: 10.1016/j.lungcan.2021.01.004. Epub 2021 Jan 10.
The prognostic value of spread through air spaces (STAS) in lung carcinoma has been validated in independent cohorts. Epithelial-mesenchymal transition (EMT) is a biological process that promotes the migration and invasiveness of tumor cells. To investigate the role of the EMT phenotype in the occurrence of STAS, we analyzed patients with therapy-naive lung adenocarcinoma and squamous cell carcinoma undergoing lobectomy (n = 635).
STAS was defined by the presence of tumor cells within air spaces in the lung parenchyma beyond the edge of the main tumor. The expression of E-cadherin, vimentin, and ®-catenin was evaluated by immunohistochemistry using tissue microarray. Tumors were classified into three EMT phenotypes (epithelial, intermediate, and mesenchymal). Recurrence-free probability and overall survival were analyzed using the log-rank test and the Cox proportional hazards model.
STAS was less frequently observed in tumors with epithelial phenotype than in those with non-epithelial phenotype (p = 0.034), and more frequent in patients with nuclear β-catenin-positive tumors (p < 0.001). The EMT phenotype was an independent prognostic factor of recurrence (mesenchymal vs. epithelial: hazard ratio [HR] = 2.27, p = 0.014; mesenchymal vs. intermediate: HR = 2.13, p = 0.019).
We have demonstrated that in patients with resected lung carcinoma, STAS was less frequent in tumors with an epithelial phenotype than in those with non-epithelial phenotype, and that the nuclear translocation of β-catenin was associated with a higher rate of STAS. The mesenchymal state was an independent predictor of high risk of recurrence in patients with STAS.
在独立队列中已经验证了空气空间扩散（STAS）在肺癌中的预后价值。上皮-间充质转化（EMT）是促进肿瘤细胞迁移和侵袭的生物学过程。为了研究 EMT 表型在 STAS 发生中的作用，我们分析了 635 例接受肺叶切除术的未经治疗的肺腺癌和鳞状细胞癌患者。
STAS 定义为肿瘤细胞存在于主肿瘤边缘以外的肺实质空气空间内。使用组织微阵列通过免疫组织化学评估 E-钙粘蛋白、波形蛋白和 β-连环蛋白的表达。肿瘤被分为三种 EMT 表型（上皮型、中间型和间充质型）。使用对数秩检验和 Cox 比例风险模型分析无复发生存率和总生存率。
与非上皮表型的肿瘤相比，具有上皮表型的肿瘤中 STAS 较少见（p=0.034），并且在核 β-连环蛋白阳性肿瘤中更为常见（p<0.001）。EMT 表型是复发的独立预后因素（间充质型与上皮型：风险比 [HR]=2.27，p=0.014；间充质型与中间型：HR=2.13，p=0.019）。
我们已经证明，在接受切除治疗的肺癌患者中，与非上皮表型的肿瘤相比，具有上皮表型的肿瘤中 STAS 较少见，并且核 β-连环蛋白的易位与 STAS 发生率较高相关。间充质状态是 STAS 患者高复发风险的独立预测因素。
