The epithelial-mesenchymal transition phenotype is associated with the frequency of tumor spread through air spaces (STAS) and a High risk of recurrence after resection of lung carcinoma
The epithelial-mesenchymal transition phenotype is associated with the frequency of tumor spread through air spaces (STAS) and a High risk of recurrence after resection of lung carcinoma
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DOI：
10.1016/j.lungcan.2021.01.004
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发表时间：
2021-01-14
期刊：
影响因子：
5.3
通讯作者：
Yokomise, Hiroyasu
中科院分区：
文献类型：
--
作者：
Ikeda, Toshihiro;Kadota, Kyuichi;Yokomise, Hiroyasu
目的：通过独立队列验证了肺癌经空气间隙扩散（STAS）的预后价值。上皮-间质转化（Epithelial-mesenchymal transition， EMT）是一个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，我们分析了接受肺叶切除术的未接受治疗的肺腺癌和鳞状细胞癌患者（n = 635）。材料和方法：STAS的定义是肿瘤细胞存在于主要肿瘤边缘以外的肺实质空气间隙内。采用组织芯片免疫组化技术检测E-cadherin、vimentin和(R)-catenin的表达。肿瘤被分为三种EMT表型（上皮、中间和间充质）。采用log-rank检验和Cox比例风险模型分析无复发概率和总生存率。结果：上皮型肿瘤中STAS的发生率低于非上皮型肿瘤（p = 0.034），核β -连环蛋白阳性肿瘤中STAS的发生率高于非上皮型肿瘤（p < 0.001）。EMT表型是复发的独立预后因素（间充质vs上皮：风险比[HR] = 2.27, p =0.014；间充质vs中间：HR = 2.13, p = 0.019）。结论：我们已经证明，在切除的肺癌患者中，上皮表型肿瘤的STAS发生率低于非上皮表型肿瘤，并且β -连环蛋白的核易位与较高的STAS发生率相关。间充质状态是STAS患者高复发风险的独立预测因子。
Objectives: 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).Materials and Methods: 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 (R)-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.Results: 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 beta-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).Conclusion: 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 beta-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.