Lymphatic spread is related to VEGF-C expression and D2-40-positive myofibroblasts in intrahepatic cholangiocarcinoma
Lymphatic spread is related to VEGF-C expression and D2-40-positive myofibroblasts in intrahepatic cholangiocarcinoma
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DOI：
10.1038/modpathol.3800985
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发表时间：
2008-03-01
期刊：
影响因子：
7.5
通讯作者：
Tsuneyoshi, Masazumi
中科院分区：
文献类型：
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作者：
Aishima, Shinichi;Nishihara, Yunosuke;Tsuneyoshi, Masazumi
在许多肿瘤中，通过淋巴管的淋巴结转移与不良结局相关。肝内胆管癌的淋巴扩散是否需要新的淋巴管的形成或淋巴管生成因子的表达尚不清楚。本研究的目的是评估88例肝内胆管癌中淋巴管生成、血管内皮生长因子-C（VEGF-C）表达和D2-40阳性肌纤维母细胞在淋巴管扩散和患者预后中的作用。我们还评估了15例转移性淋巴结中VEGF-C的表达。肿瘤中心淋巴管密度低与淋巴管浸润阳性之间有显著相关性（P = 0.0100）。低分化胆管癌肿瘤周围和瘤周区域淋巴管密度较高（分别为P = 0.0315和P = 0.0360）。淋巴管浸润在瘤周（63%，24/38）和肿瘤周围（79%，30/38）高于肿瘤中心（27%，9/ 38）。VEGF-C的表达与淋巴结浸润密切相关（P = 0.0006），其中12例（80%）转移淋巴结中VEGF-C阳性表达。淋巴结转移与D2-40阳性肌成纤维细胞相关（P = 0.0161）。多因素生存分析显示VEGF-C表达是独立的预后因素（P = 0.0131）。我们的研究结果表明，VEGF-C通过肿瘤边缘的预先存在的淋巴管在淋巴侵袭中具有重要作用，并且淋巴管生成在淋巴转移中不起直接作用。D2-40阳性肌成纤维细胞可能参与淋巴转移。
Lymph node metastasis via lymphatic vessels is related with an adverse outcome in many tumors. It is unclear whether lymphatic spread needs the development of the new lymphatic vessels or the expression of lymphangiogenetic factor in intrahepatic cholangiocarcinoma. The aim of this study was to assess the role of lymphangiogenesis, vascular endothelial growth factor-C (VEGF-C) expression, and D2-40-positive myofibroblastic cells for lymphatic spread and patient outcome in 88 cases of intrahepatic cholangiocarcinoma. We also assessed VEGF-C expression in 15 cases of metastatic lymph nodes. There was a significant correlation between lower lymphatic vessel density in the tumor center and positive lymphatic invasion (P = 0.0100). Poorly differentiated cholangiocarcinoma showed higher lymphatic vessel density in the tumor periphery and in the peritumoral area (P = 0.0315 and P = 0.0360, respectively). Lymphatic invasion was observed higher in the peritumoral area (63%, 24/38) and in the tumor periphery (79%, 30/38) than in the tumor center (27%, 9/ 38). There was no significant correlation between the proliferative lymphatic vessels and pathologic features; however, lymphatic invasion was significantly associated with VEGF-C expression (P = 0.0006), and the VEGF-C expression was seen in 12 of 15 cases (80%) of metastatic lymph node. Nodal metastasis was correlated with D2-40-positive myofibroblasts (P = 0.0161). VEGF-C expression was an independent prognostic factor by multivariate survival analysis (P = 0.0131). Our findings suggest that VEGF-C has an important role in lymphatic invasion via the preexisting lymphatic vessels in the tumor margin, and that lymphangiogenesis does not play a direct role in lymphatic metastasis. D2-40-positive myofibroblasts may contribute to lymphatic metastasis.