[To evaluate the clinicopathologic characteristics and outcome of tumor cells spreading through air spaces in patients with adenocarcinoma of lung].

Objective: To investigate the clinicopathologic features, molecular characteristics and prognosis of spread through air space (STAS) in patients with adenocarcinoma of the lung. Methods: 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. Results: 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 (P=0.009), and was significantly higher in tumors with pleural invasion (P<0.01), venous invasion (P<0.01), lymphatic invasion (P<0.01), perineural invasion (P=0.029) and tumors with necrosis (P<0.01). STAS was also correlated with tumor recurrence (P<0.01) and advanced pathologic TNM stage (P=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 (P<0.01). STAS was significantly higher in EGFR negative group (P=0.034), ALK gene rearrangement group (P=0.003) and ROS1 gene rearrangement group (P=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, P<0.01) and overall survival (P=0.013). Multivariate analysis confirmed that STAS was an independent predictor of PFS in lung adenocarcinoma patients (HR: 2.749, 95%CI: 1.550-4.876, P=0.001). Conclusions: 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.目的： 研究肿瘤细胞气腔内播散(spread through air spaces，STAS)与肺腺癌患者临床病理学特征、分子学特征以及患者预后之间的关系。 方法： 收集2010年1月至2014年12月确诊的肺腺癌患者手术切除标本，选择具有完整临床病理学资料及随访资料的肺腺癌288例，将病例分为STAS阳性组(178例)和阴性组(110例)。表皮生长因子受体(EGFR)、KRAS基因突变采用突变扩增阻滞系统(ARMS)方法进行检测，间变性淋巴瘤激酶(ALK)及ROS1基因融合采用荧光原位杂交(FISH)方法进行检测。分析STAS与患者临床病理学特征、分子学特征以及生存之间的关系。 结果： STAS存在于61.8%(178/288)的肺腺癌病例中，STAS在直径>3 cm的肿瘤中阳性率明显高于肿瘤直径≤3 cm的肿瘤(P＝0.009)。并且存在肿瘤胸膜浸润(P<0.01)、血管浸润(P<0.01)、淋巴管浸润(P<0.01)、神经周围浸润(P＝0.029)肿瘤中阳性率明显高于无浸润组。另外具有肿瘤性坏死的肿瘤中STAS阳性率高于肿瘤坏死阴性组(P<0.01)。STAS还与肿瘤复发(P<0.01)以及更晚的病理学TNM分期(P＝0.002)具有明显相关性。而与患者性别、年龄及有无吸烟史无关。组织学类型分析结果显示STAS在腺泡型、乳头型、附壁型、实性型以及微乳头型腺癌中的阳性率分别为58.0%(91/157)、67.6%(50/74)、2/6、64.3%(27/42)以及8/9。另外在存在微乳头成分与不存在微乳头成分(>5%)腺癌中的阳性率分别为80.9%(55/68)和55.9%(123/220，P<0.01)。分析不同基因亚型肺腺癌中STAS的存在情况，STAS在EGFR突变阴性组患者中阳性率明显高于阳性组(P＝0.034)，在ALK基因重排阳性患者中阳性率明显高于基因重排阴性患者(P＝0.003)，在ROS1基因重排阳性患者中阳性率也明显高于ROS1阴性患者(P＝0.012)，而与KRAS基因突变无明显相关性。单因素生存分析结果显示STAS阳性患者具有更短的无进展生存期(P<0.01)及总生存期(P＝0.013)。多因素分析证实了STAS可以作为一个独立的预后因素预测患者的无进展生存(HR：2.749，95% CI：1.550～4.876，P＝0.001)。 结论： 肺腺癌中存在STAS提示肿瘤具有高度侵袭和复发行为，并且是影响预后的重要因素。另外STAS与EGFR突变、ALK及ROS1基因重排具有相关性。.