你还不知道，肺癌侵袭转移的最新研究热点--STAS？

肺癌是全球常见的恶性肿瘤之一，严重威胁着人们的健康。而肺癌的不良预后与肿瘤的浸润和转移息息相关。但就目前的研究而言，肺癌侵袭转移的机制仍未研究清楚。2015年WHO肺肿瘤组织分类正式将肿瘤经肺泡腔隙扩散 ( tumor spread through air space, STAS ) 正式作为一种新的肺腺癌浸润方式。STAS的定义为肿瘤细胞经肺泡腔隙向肿瘤主体边缘以外的肺组织内扩散，肿瘤细胞通常形成微乳头结构、实性肿瘤细胞岛或单个肿瘤细胞扩散。

STAS 在肺癌中的作用

目前关于STAS的文章也越来越多。STAS在肺腺癌中的研究显示其的巨大临床意义。Warth等的研究通过评估569名肺腺癌患者，发现将近一半的患者出现STAS，其中21.6%为肿瘤沿肺泡腔隙局限性扩散，29%为肿瘤沿肺泡腔隙广泛性扩散，研究认为STAS与肺腺癌的远处转移、分期及不良预后等有紧密联系。

Kadota等的研究发现，在接受局限性肺切除的肺腺癌患者中，STAS阳性患者比STAS阴性患者有更高的远处转移的风险；相比之下，在接受肺叶切除的患者中，STAS阳性或阴性对患者的远处转移无明显影响。这表明STAS是肺腺癌患者发生远处或局部转移的重要影响因素。

Toyokawa等报道，82名进行局部切除的早期肺腺癌患者中有31名 ( 37.8% ) 出现STAS；研究通过评估STAS的临床病理特征与术后生存的关系发现，STAS与恶性病理特征如高级别、低分化、肺癌胸膜转移等有重要的联系；并且出现STAS的患者总生存期与无复发生存期大大降低。

STAS在腺癌中的形态

( 图片来自Toyokawa et al. Significance of Spread Through Air Spaces in Resected Pathological Stage I Lung Adenocarcinoma )

不只是腺癌，STAS也出现在其他多种肺癌癌种中。STAS在鳞癌中均表现为实性肿瘤细胞岛。Lu等对445名I期到II期进行切除的肺鳞癌患者进行分析，其中30%的患者出现STAS。与肺腺癌相比较，STAS在鳞癌中要表现为实性肿瘤细胞岛。并且，STAS在鳞癌中与病理分期、淋巴及血道转移、巨形细胞核等肿瘤的侵袭性均有关。Kadota等报道STAS不仅与肿瘤的侵袭性有关，而且是判断进行切除的肺鳞癌患者的预后如无复发生存期的重要判断因素。根据Yanagawa的报道，针对一期鳞癌，STAS是复发和预后的有效预测因素，但对二期、三期鳞癌患者无预测复发和预后的作用。

STAS在鳞癌中的表现 

 ( 图片来自Shaohua Lu et al. Spread through Air Spaces (STAS) Is an Independent Predictor of Recurrence and Lung Cancer–Specific Death in Squamous Cell Carcinoma )

然而，在小细胞肺癌的研究中，就目前的数据而言，STAS对小细胞肺癌患者的术后生存期无影响。

此外，在肺多形性癌的研究中，Yokoyama等对35名肺多形性癌患者进行研究，14名 ( 40% ) 患者出现STAS，均观察到微乳头结构、实性肿瘤细胞岛及单个肿瘤细胞扩散。STAS与手术切除后的肺多形性癌患者的高复发率及不良预后有联系；因此，STAS可作为术后生存的预测因素之一。

由于病理医生几乎很少在肺腺癌组织周围的肺泡中寻找肿瘤细胞，STAS在显微镜视野下鲜有被观察到。此外，数据的缺乏使STAS这一现象并未得到足够的重视。因此在制作组织切片时，应注意保留肿瘤组织的边缘及周围的肺实质，并识别肺泡腔内肿瘤细胞，以寻找STAS。

关于 STAS 的思考

尽管对STAS的研究众多，仍有相当多的学者认为，STAS是一种假象 ( artifact ) 。有文献报道，在病理诊断过程中，1.2%切片可能会发生诊断错误，原因可能是活检步骤、外科操作、病理切片制作过程导致的组织切片的污染，这些污染大部分来自外界而非病人本身的组织。很早以前，病理学家就在肺癌组织切片中观察到游离组织碎片，并将其解释为假象。Warth等认为在对肿瘤的手术操作过程中，许多外科器械的使用均可导致肿瘤的位置改变；外科医生为了定位肺叶中的小肿瘤，会用手对肺组织施压，由于肿瘤组织松散的性质，这一操作毫无疑问会使肿瘤扩散到相邻肺泡。因此，也有人认为STAS并不是肿瘤经肺泡腔隙扩散，而是肿瘤经外科医生扩散 ( spread througha surgeon ) 。

肺癌居高不下的死亡率和发病率，以及肺癌预后状况不良的现状对肺癌转移的机制研究的需求日益迫切。而STAS作为一种全新的肺癌侵袭方式的相关研究，尚未得到足够重视。因此，对STAS与肺癌的浸润与复发的深入研究，不仅能为肺癌的预后提供独立的判断因素，还能完善肺癌的pTNM分期，为临床治疗提供指导。

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