Prognostic significance of microvascular invasion and microlymphatic permeation in non-small-cell lung cancer.
Prognostic significance of microvascular invasion and microlymphatic permeation in non-small-cell lung cancer.
复制标题
非小细胞肺癌微血管侵犯和微淋巴渗透的预后意义。
DOI：
10.1093/ejcts/ezs632
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发表时间：
2013
影响因子：
3.4
通讯作者：
Kainan Li
中科院分区：
文献类型：
--
作者：
Jun Wang;Baocheng Wang;Jing;Kainan Li
我们饶有兴趣地阅读了Hishida等人最近发表的回顾研究。[1]。作者回顾了1039例T1A-3N0M0期非小细胞肺癌(NSCLC)患者的资料，认为微血管侵犯和微淋巴管渗透对预后有不同的影响。我们对病理性微血管侵袭和微淋巴管渗透的方法学感兴趣。在这篇文章中，作者使用苏木精-伊红和维多利亚蓝-范-吉森(VVG)染色来评估微血管的侵袭。通过识别被VVG染色的弹性层包围的明显的血管内癌细胞簇来确定微血管侵犯的存在。如果肿瘤细胞存在于VVG阴性、内皮细胞衬里的细小通道内，而不支持平滑肌肉或弹性纤维，则微淋巴管渗透被认为是阳性。仅通过苏木素和伊红染色基本上不可能可靠地区分淋巴管通道和包括毛细血管和毛细血管后小静脉在内的小血管，也不能可靠地区分淋巴管和人造基质回缩。作者注意到了这个问题，并认为当在支气管血管束、胸膜下或小叶间胸膜间隙的管腔中发现浮动的肿瘤细胞时，淋巴渗透被认为是存在的。弹性染色通常被用来帮助识别较大的血管，但它们在排除毛细血管方面用处较小，在区分间质回缩和真正的淋巴间隙方面也没有用。因此，这一方法问题可能会降低结果和结论的合理性和可靠性。最近，一些研究使用免疫组织化学标记物，如CD34来识别血管[2]，D2-40来识别淋巴管内皮细胞[3]。这些特异性标志物可能有助于提高检测和区分微血管侵犯和微淋巴管渗入的准确性。Hishida等人。发现微血管侵犯(危险比[HR]：1.65，P=0.001)而不是微淋巴管渗透(HR：1.14，P=0.588)对患者的预后有重要影响。在一项涉及52项研究的16例病例的荟萃分析[4]中，我们得出结论，尽管在I期非小细胞肺癌患者中，复发(HR：6.93，P=0.0001)和死亡(HR：2.15，P=0.0001)的Meta风险仍具有高度统计学意义，但多因素估计总生存率为1.9(P=0.0001)。Hishida等人的观察。与我们的结果相一致的是，有微血管侵犯的NSCLC患者可以受益于辅助全身化疗，这一病理标志物应纳入新版的TNM分类。然而，我们认为预后意义并不局限于T1A-3N0M0期非小细胞肺癌患者。此外，通过对这些因素的单独评估，作者的结果显示微血管侵犯比微淋巴管渗透对生存率的影响更大。应在其他中心提出更多使用类似方法的比较研究，并考虑进行荟萃分析以验证其结论。我们认为，在非小细胞肺癌患者中，微血管侵犯可能导致复发和死亡风险的增加。需要使用标准方法和质量控制来评估淋巴管侵袭的大型、设计合理的研究，以证明淋巴管侵袭和微淋巴管渗透是否可以提供预后信息。
We read with interest the recently published retrospective study by Hishida et al. [1]. The authors reviewed the data of 1039 patients with stage T1a-3N0M0 non-small-cell lung cancer (NSCLC) and concluded that microvascular invasion and microlymphatic permeation had different impact on the outcome. We are interested with the methodology of pathological microvascular invasion and microlymphatic permeation. In this article, the authors used haematoxylin and eosin and Victoria blue-van Gieson (VVG) staining to evaluate microvascular invasion. The presence of microvascular invasion was determined by identifying conspicuous clusters of intravascular cancer cells surrounded by a VVG-stained elastic layer. Microlymphatic permeation was considered to be positive if tumour cells were present inside VVG-negative, thin endothelial-lined channels without supporting smooth muscles or elastic fibres. It is essentially impossible by haematoxylin and eosin staining alone to reliably distinguish lymphatic channels from small blood vessels including capillaries and post-capillary venules or from artefactual stromal retraction. The authors noted this problem and considered that lymphatic permeation was concluded to be present when floating tumour cells were found in lumens within the bronchovascular bundle, subpleural or interlobular pleural spaces. Elastic stains are routinely used to help identify larger blood vessels, but they are less useful in excluding capillaries and are not useful in making the distinction between stromal retraction and true lymphatic spaces. Thus, this methodological issue could decrease the rationale and reliability of the results and conclusions. More recently, some studies used immunohistochemical markers such as CD34 to specifically identify blood vessels [2] and D2-40 to identify lymphatic endothelium [3]. These specific markers might be of value in improving the accuracy of detecting and distinguishing between microvascular invasion and microlymphatic permeation. Hishida et al. found that microvascular invasion (hazard ratio [HR]: 1.65, P = 0.001), but not microlymphatic permeation (HR: 1.14, P = 0.588), had an important effect on the prognosis of patients. In a meta-analysis involving 16 535 cases from 52 studies [4], we concluded that the multivariate estimate for overall survival was 1.90 (P = 0.0001), although in Stage I NSCLC patients, the meta-risk of recurrence (HR: 6.93, P = 0.0001) and death (HR: 2.15, P = 0.0001) remained highly statistically significant. The observations of Hishida et al. correspond with our results in which NSCLC patients with microvascular invasion can benefit adjunct systematic chemotherapy, and this pathological marker should be incorporated in the new edition of the TNM classification. However, we suggest that the prognostic significance not be restricted to stage T1a-3N0M0 NSCLC patients. In addition, through assessing these factors separately, the authors’ results showed that microvascular invasion had more impact on survival than microlymphatic permeation. More comparison studies using similar methods should be presented in other centres, and a meta-analysis also be considered to verify their conclusions. We believe that, in NSCLC patients, microvascular invasion may have led to an increase in the risk of recurrence and death. Large, properly designed studies that employ standard methodology and quality control to assess lymphvascular invasion are required in demonstrating whether lymphovascular invasion and microlymphatic permeation can provide prognostic information.