Bono Petri, Wasenius Veli-Matti, Heikkilä Päivi, Lundin Johan, Jackson David G, Joensuu Heikki
Department of Oncology, Helsinki University Central Hospital, Helsinki, Finland.
Clin Cancer Res. 2004 Nov 1;10(21):7144-9. doi: 10.1158/1078-0432.CCR-03-0826.
The clinical significance of intratumoral or peritumoral lymph vessel density is not known. LYVE-1, a lymphatic endothelium-specific hyaluronan receptor, is a novel lymphatic vessel marker that is expressed on lymph vessel endothelial cells of both normal and neoplastic tissues.
We investigated expression of LYVE-1 by immunohistochemistry in 180 unilateral, invasive ductal breast carcinomas and assessed the presence and density of lymph vessels within the tumor and at the tumor periphery.
A minority (12%) of breast carcinomas had intratumoral lymph vessels, whereas peritumoral lymph vessels were identified in almost all cases (94%). No substantial association was found between the number of LYVE-1-positive vessels and the number of CD31 or vascular endothelial growth factor receptor-3-positive vessels, or vascular endothelial growth factor-C expression. The number of metastatic axillary lymph nodes increased in parallel with increasing lymph vessel counts (P = 0.033). A higher than the median lymph vessel count at the tumor periphery was significantly associated with unfavorable distant disease-free survival and overall survival. Women with high peritumoral lymph vessel density had only 58% (95% confidence interval, 46-70%) 5-year distant disease-free survival as compared with 74% (66-83%) among those with a low peritumoral lymph vessel density (P = 0.0088). In contrast, the presence of intratumoral lymph vessels was associated with neither axillary nodal status nor survival. Lymph vessel density was not an independent prognostic factor in a multivariate survival analysis.
A high peritumoral lymph vessel density is associated with a poor outcome in ductal breast cancer.
肿瘤内或肿瘤周围淋巴管密度的临床意义尚不清楚。LYVE-1是一种淋巴管内皮特异性透明质酸受体,是一种新型的淋巴管标志物,在正常组织和肿瘤组织的淋巴管内皮细胞上均有表达。
我们采用免疫组织化学方法研究了180例单侧浸润性导管乳腺癌中LYVE-1的表达情况,并评估了肿瘤内及肿瘤周边淋巴管的存在情况和密度。
少数(12%)乳腺癌存在肿瘤内淋巴管,而几乎所有病例(94%)均可发现肿瘤周围淋巴管。未发现LYVE-1阳性血管数量与CD31或血管内皮生长因子受体-3阳性血管数量或血管内皮生长因子-C表达之间存在显著关联。腋窝转移性淋巴结数量随淋巴管计数增加而平行增加(P = 0.033)。肿瘤周边淋巴管计数高于中位数与远处无病生存率和总生存率不良显著相关。肿瘤周围淋巴管密度高的女性5年远处无病生存率仅为58%(95%置信区间,46 - 70%),而肿瘤周围淋巴管密度低的女性为74%(66 - 83%)(P = 0.0088)。相比之下,肿瘤内淋巴管的存在与腋窝淋巴结状态及生存率均无关。在多因素生存分析中,淋巴管密度不是独立的预后因素。
肿瘤周围淋巴管密度高与导管乳腺癌预后不良相关。