Thelen Armin, Scholz Arne, Benckert Christoph, Weichert Wilko, Dietz Ekkehart, Wiedenmann Bertram, Neuhaus Peter, Jonas Sven
Department of General, Visceral and Transplantation Surgery, Campus Virchow-Klinikum, Charité Universitaetsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Germany.
Ann Surg Oncol. 2008 Mar;15(3):791-9. doi: 10.1245/s10434-007-9774-0. Epub 2008 Jan 3.
Tumor-associated lymphangiogenesis has been shown to promote nodal spread and is of prognostic significance in some tumor entities. Currently, nothing is known about the impact of lymphangiogenesis on progression and prognosis in hilar cholangiocarcinoma.
We analyzed tissue specimens of normal liver and hilar cholangiocarcinoma (n = 60) by immunohistochemistry using the lymphendothelial-specific antibody D2-40 and subsequently quantified lymphatic microvessel density (LVD). The LVD was correlated with clinicopathological characteristics and recurrence pattern of the tumors as well as patients' survival.
In contrast to the low abundance of lymphatic vessels in nontransformed liver tissue, we found an induction of lymphangiogenesis in hilar cholangiocarcinoma. Tumors with a high LVD (34 out of 60) had a significant higher incidence of lymph node involvement (p < 0.001), perivascular (p = 0.017), and perineural (p = 0.033) lymphangiosis and local recurrence (p < 0.001). Furthermore, a high LVD was identified to be a significant overall (three-year: 24.4% versus 90.5%; five-year: 7.0% versus 76.4%; p < 0.001) and disease-free (three-year: 8.3% versus 76.6%; five-year: 5.9% versus 61.4%; p < 0.001) survival disadvantage, with LVD representing an independent prognostic factor for survival (p < 0.001) in the multivariate analysis.
Lymphangiogenesis is associated with increased frequency of tumor cells in lymphatics and lymph nodes in hilar cholangiocarcinoma. The prognostic importance of tumor-associated lymphangiogenesis was reflected by LVD serving as an independent prognostic factor. In addition, lymphangiogenesis may represent a potential target in the development of new therapeutic approaches in hilar cholangiocarcinoma.
肿瘤相关淋巴管生成已被证明可促进淋巴结转移，并且在某些肿瘤实体中具有预后意义。目前，关于淋巴管生成对肝门部胆管癌进展和预后的影响尚不清楚。
我们使用淋巴管内皮特异性抗体D2-40通过免疫组织化学分析了正常肝脏和肝门部胆管癌（n = 60）的组织标本，随后对淋巴管微血管密度（LVD）进行了量化。将LVD与肿瘤的临床病理特征、复发模式以及患者的生存率进行关联分析。
与未发生病变的肝组织中淋巴管数量较少形成对比，我们发现肝门部胆管癌中存在淋巴管生成。LVD高的肿瘤（60例中有34例）淋巴结受累（p < 0.001）、血管周围（p = 0.017）和神经周围（p = 0.033）淋巴管增生以及局部复发（p < 0.001）的发生率显著更高。此外，高LVD被确定为总体生存（三年：24.4% 对 90.5%；五年：7.0% 对 76.4%；p < 0.001）和无病生存（三年：8.3% 对 76.6%；五年：5.9% 对 61.4%；p < 0.001）的显著不利因素，在多变量分析中，LVD是生存的独立预后因素（p < 0.001）。
淋巴管生成与肝门部胆管癌淋巴管和淋巴结中肿瘤细胞频率增加相关。肿瘤相关淋巴管生成的预后重要性通过LVD作为独立预后因素得以体现。此外，淋巴管生成可能是肝门部胆管癌新治疗方法开发中的一个潜在靶点。
