Sun P L, Liu J N, Cao L Q, Yao M, Gao H W
Department of Pathology, the Second Hospital of Jilin University, Changchun 130021, China.
Zhonghua Bing Li Xue Za Zhi. 2017 May 8;46(5):303-308. doi: 10.3760/cma.j.issn.0529-5807.2017.05.004.
To investigate the clinicopathologic features, molecular characteristics and prognosis of spread through air space (STAS) in patients with adenocarcinoma of the lung. Two hundred and eighty-eight lung adenocarcinoma patients with complete clinicopathologic and follow-up data were included. The patients were divided into STAS positive (178 cases) and negative (110 cases) groups.EGFR and KRAS gene mutations were detected by amplification refractory mutation system (ARMS), and ALK and ROS1 gene fusion were detected by fluorescence in situ hybridization method. The relationship between STAS and clinicopathologic, molecular features, and patient outcome was analyzed. STAS was present in 61.8%(178/288) of lung adenocarcinomas. The positive rate of STAS in tumors >3 cm was significantly higher than that in tumors ≤3 cm (=0.009), and was significantly higher in tumors with pleural invasion (<0.01), venous invasion (<0.01), lymphatic invasion (<0.01), perineural invasion (=0.029) and tumors with necrosis (<0.01). STAS was also correlated with tumor recurrence (<0.01) and advanced pathologic TNM stage (=0.002). There was no significant correlation with patients' gender, age and smoking history. Histologically, STAS was present in 58.0%(91/157), 67.6%(50/74), 2/6, 64.3%(27/42) and 8/9 of acinar, papillary, lepidic, solid and micropapillary adenocarcinomas, respectively. In addition, the positive rates of STAS in tumor with micropapillary (>5%) and without micropapillary pattern were 80.9%(55/68) and 55.9%(123/220), respectively (<0.01). STAS was significantly higher in EGFR negative group (=0.034), ALK gene rearrangement group (=0.003) and ROS1 gene rearrangement group (=0.012), but there was no significant correlation with KRAS mutation. Univariate survival analysis showed that patients with STAS had a shorter progression-free survival (PFS, <0.01) and overall survival (=0.013). Multivariate analysis confirmed that STAS was an independent predictor of PFS in lung adenocarcinoma patients (: 2.749, 95%: 1.550-4.876, =0.001). The presence of STAS in lung adenocarcinoma suggests high risk of recurrence and invasion and is thus an important prognostic factor. In addition, STAS is associated with EGFR mutation, ALK and ROS1 gene rearrangement.
探讨肺腺癌患者气腔播散（STAS）的临床病理特征、分子特征及预后。纳入288例具有完整临床病理及随访资料的肺腺癌患者。将患者分为STAS阳性组（178例）和阴性组（110例）。采用扩增阻滞突变系统（ARMS）检测EGFR和KRAS基因突变，采用荧光原位杂交法检测ALK和ROS1基因融合。分析STAS与临床病理、分子特征及患者预后的关系。61.8%（178/288）的肺腺癌存在STAS。肿瘤>3 cm的STAS阳性率显著高于肿瘤≤3 cm的（=0.009），且在有胸膜侵犯（<0.01）、静脉侵犯（<0.01）、淋巴侵犯（<0.01）、神经侵犯（=0.029）及有坏死的肿瘤（<0.01）中显著更高。STAS还与肿瘤复发（<0.01）及高级别病理TNM分期（=0.002）相关。与患者的性别、年龄及吸烟史无显著相关性。组织学上，腺泡状、乳头状、贴壁状、实体状及微乳头状腺癌中STAS的存在率分别为58.0%（91/157）、67.6%（50/74）、2/6、64.3%（27/42）及8/9。此外，有微乳头（>5%）和无微乳头模式的肿瘤中STAS阳性率分别为80.9%（55/68）和55.9%（123/220）（<0.01）。EGFR阴性组（=0.034）、ALK基因重排组（=0.003）及ROS1基因重排组中STAS显著更高，但与KRAS突变无显著相关性。单因素生存分析显示，STAS患者的无进展生存期（PFS，<0.01）和总生存期（=0.013）较短。多因素分析证实，STAS是肺腺癌患者PFS的独立预测因素（：2.749，95%：1.550 - 4.876，=0.001）。肺腺癌中STAS的存在提示复发和侵袭风险高，因此是一个重要的预后因素。此外，STAS与EGFR突变、ALK和ROS1基因重排相关。
