Tumor lymphangiogenesis - A novel prognostic indicator for cutaneous melanoma metastasis and survival
Tumor lymphangiogenesis - A novel prognostic indicator for cutaneous melanoma metastasis and survival
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DOI：
10.1016/s0002-9440(10)64328-3
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发表时间：
2003-06-01
影响因子：
6
通讯作者：
Detmar, M
中科院分区：
文献类型：
--
作者：
Dadras, SS;Paul, T;Detmar, M
皮肤恶性黑色素瘤的特点是其早期转移倾向通过淋巴管扩散到区域淋巴结，淋巴结转移是黑色素瘤分期和临床管理的主要决定因素。然而，肿瘤诱导的淋巴管生成对淋巴黑色素瘤扩散的重要性仍不清楚。我们研究了肿瘤淋巴管生成是否发生在人类皮肤恶性黑色素瘤中，以及肿瘤淋巴管生成的程度是否与淋巴结转移的风险和患者生存有关，使用了新的淋巴内皮标记物LYVE-1和全血管标记物CD31的双重免疫染色。肿瘤样本来自临床和组织学上密切匹配的早期淋巴结转移的原发性黑色素瘤（n = 18）和非转移性黑色素瘤（n = 19）。大量黑色素瘤中可见肿瘤内及肿瘤周围淋巴管增生热点。转移性黑色素瘤的瘤内淋巴管发生率明显较高，并与较差的无病生存率相关。转移性黑色素瘤有更多更大的肿瘤相关淋巴管，相对淋巴管面积为bbbb1.5 %与较差的无病生存率和总生存率显著相关。相比之下，没有发现肿瘤相关血管密度的差异。在两组的少数病例中，血管内皮生长因子和血管内皮生长因子- c的表达相同。我们的研究结果显示肿瘤淋巴管生成是皮肤黑色素瘤淋巴结转移风险的一种新的预后指标。（美国病理学杂志，2003,162:1951-1960）
Malignant melanomas of the skin are distinguished by their propensity for early metastatic spread via lymphatic vessels to regional lymph nodes, and lymph node metastasis is a major determinant for the staging and clinical management of melanoma. However, the importance of tumor-induced lymphangiogenesis for lymphatic melanoma spread has remained unclear. We investigated whether tumor lymphangiogenesis occurs in human malignant melanomas of the skin and whether the extent of tumor lymphangiogenesis may be related to the risk for lymph node metastasis and to patient survival, using double immunostains for the novel lymphatic endothelial marker LYVE-1 and for the panvascular marker CD31. Tumor samples were obtained from clinically and histologically closely matched cases of primary melanomas with early lymph node metastasis (n = 18) and from non-metastatic melanomas (n = 19). Hot spots of proliferating intratumoral and peritumoral lymphatic vessels were detected in a large number of melanomas. The incidence of intratumoral lymphatics was significantly higher in metastatic melanomas and correlated with poor disease-free survival. Metastatic melanomas had significantly more and larger tumor-associated lymphatic vessels, and a relative lymphatic vessel area of >1.5% was significantly associated with poor disease-free and overall survival. In contrast, no differences in the density of tumor-associated blood vessels were found. Vascular endothelial growth factor and vascular endothelial growth factor-C expression was equally detected in a minority of cases in both groups. Our results reveal tumor lymphangiogenesis as a novel prognostic indicator for the risk of lymph node metastasis in cutaneous melanoma. (Am J Pathol 2003, 162:1951-1960)