Aishima Shinichi, Nishihara Yunosuke, Iguchi Tomohiro, Taguchi Kenichi, Taketomi Akinobu, Maehara Yoshihiko, Tsuneyoshi Masazumi
Department of Pathology, Hamanomachi Hospital, Fukuoka, Japan.
Mod Pathol. 2008 Mar;21(3):256-64. doi: 10.1038/modpathol.3800985. Epub 2008 Jan 11.
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.
通过淋巴管发生的淋巴结转移与许多肿瘤的不良预后相关。肝内胆管癌中淋巴管扩散是否需要新生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淋巴管生成、血管内皮生长因子-C（VEGF-C）表达和D2-40阳性肌成纤维细胞在88例肝内胆管癌的淋巴管扩散及患者预后中的作用。我们还评估了15例转移性淋巴结中的VEGF-C表达。肿瘤中心较低的淋巴管密度与阳性淋巴管侵犯之间存在显著相关性（P = 0.0100）。低分化胆管癌在肿瘤周边和瘤周区域显示出较高的淋巴管密度（分别为P = 0.0315和P = 0.0360）。瘤周区域（63%，24/38）和肿瘤周边（79%，3 /38）的淋巴管侵犯高于肿瘤中心（27%，9/38）。增殖性淋巴管与病理特征之间无显著相关性；然而，淋巴管侵犯与VEGF-C表达显著相关（P = 0.0006），并且在15例转移性淋巴结中的12例（80%）中可见VEGF-C表达。淋巴结转移与D2-40阳性肌成纤维细胞相关（P = 0.0161）。通过多因素生存分析，VEGF-C表达是一个独立的预后因素（P = 0.0131）。我们的研究结果表明，VEGF-C在通过肿瘤边缘预先存在的淋巴管进行的淋巴管侵犯中起重要作用，并且淋巴管生成在淋巴转移中不发挥直接作用。D2-40阳性肌成纤维细胞可能有助于淋巴转移。
