Department of Liver Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, 1630 Dongfang Road, Shanghai, 200127, China.
BMC Cancer. 2019 Mar 8;19(1):208. doi: 10.1186/s12885-019-5420-z.
Tumor-associated lymphangiogenesis is considered significant in number of solid malignancies. However, its impact on prognosis of intrahepatic cholangiocarcinoma (ICC) after resection remains further confirmation. Herein, we conducted this study to evaluate prognostic impact of tumor-associated lymphangiogenesis in patients with ICC.
Extent of tumor-associated lymphangiogenesis of ICC was evaluated by quantifying microlymphatic vessel density (MLVD) from immunohistochemical staining of a lymphatic endothelial-specific antibody (podoplanin). Clinicopathological characteristics were comprehensively analyzed to identify MLVD-associated factors. The patients were stratified into high and low MLVD groups according to the distinctive correlation between the MLVD and overall survival using the Spearman's correlation test. Kaplan-Meier estimation was performed to confirm prognostic impact of MLVD in patients with ICC. Univariate and multivariate analyses were performed using the Cox proportional hazard model.
The MLVD between 4 to 12 counts showed inverse proportion to the overall survival (Spearman's r = - 0.66; 95% confidence interval [CI], - 0.82 to - 0.39; p < 0.0001), which was set as a cut-off for the high MLVD group, whereas the MLVD between 13 to 25 showed no correlation to the overall survival (r = - 0.11; 95% CI, - 0.38 to 0.19; p = 0.4791). The high MLVD group showed more frequent lymph node metastasis (p < 0.001) and were more likely to suffer from recurrence of the tumor compared to the low MLVD group (p < 0.001). The high MLVD was found to be independently associated with reduced overall and recurrence-free survival. The 5-year overall survival of the patients with high MLVD was significantly lower compared to those with low MLVD (0% vs 48%).
Our study reveals that tumor-associated lymphangiogenesis is significantly associated with increased lymphatic metastasis, recurrence of the tumor, and reduced overall survival in patients with ICC, thus providing guidance when estimating postresection prognosis.
肿瘤相关淋巴管生成在许多实体恶性肿瘤中数量显著。然而，其对切除后肝内胆管癌（ICC）预后的影响仍需进一步证实。在此，我们进行了这项研究，以评估 ICC 患者肿瘤相关淋巴管生成对预后的影响。
通过对淋巴管内皮特异性抗体（podoplanin）的免疫组化染色来评估 ICC 肿瘤相关淋巴管生成的程度，从而量化微淋巴管密度（MLVD）。综合分析临床病理特征，以确定与 MLVD 相关的因素。根据 MLVD 与总生存时间之间的显著相关性，采用 Spearman 相关检验将患者分为高 MLVD 组和低 MLVD 组。采用 Kaplan-Meier 估计法证实 MLVD 对 ICC 患者预后的影响。采用 Cox 比例风险模型进行单因素和多因素分析。
MLVD 为 4 至 12 计数与总生存时间呈反比（Spearman r= -0.66；95%置信区间[CI]，-0.82 至 -0.39；p < 0.0001），将其设为高 MLVD 组的截断值，而 MLVD 为 13 至 25 与总生存时间无相关性（r= -0.11；95% CI，-0.38 至 0.19；p= 0.4791）。高 MLVD 组淋巴结转移更频繁（p < 0.001），且与低 MLVD 组相比，肿瘤复发的可能性更高（p < 0.001）。高 MLVD 与总生存时间和无复发生存时间的降低独立相关。高 MLVD 患者的 5 年总生存率明显低于低 MLVD 患者（0% vs 48%）。
本研究表明，肿瘤相关淋巴管生成与 ICC 患者淋巴管转移、肿瘤复发和总生存时间降低显著相关，为评估术后预后提供了指导。
