Department of General Surgery, Changhai Hospital, Second Military Medical University, Shanghai, China.
Cancer Sci. 2012 Oct;103(10):1756-63. doi: 10.1111/j.1349-7006.2012.02364.x. Epub 2012 Aug 27.
Cancer cells can metastasize throughout the body by various mechanisms, including the lymphatic system, resulting in tumor-induced lymphangiogenesis that can profoundly affect patient survival. The aim of the present study was to examine the role of lymphangiogenesis in the metastasis of pancreatic cancer to the peripheral nerve plexus. Immunohistochemistry was performed to analyze specimens obtained from 70 ductal adenocarcinoma patients. The markers used included lymphangiogenic factor vascular endothelial growth factor (VEGF)-C, the lymphatic-specific marker D2-40, and cytokeratin 19, an independent prognostic factor for pancreatic tumors. The relationship between survival rate and invasion of both the lymphatic vessels and peripancreatic nerve plexus (PNP) was evaluated, with clearly elevated lymphatic vessel density (LVD) in tissues adjacent to the cancer tissues. In fact, LVD levels were higher in adjacent tissues than in localized cancer tissues, and lymphatic vessel invasion into tissues adjacent to the tumor was significantly correlated with both PNP invasion (P = 0.005) and lymph node metastasis (P = 0.010). Correspondingly, LVD in tissues adjacent to the tumor was correlated with both invasion of lymphatic vessels surrounding the tumor (P = 0.024) and VEGF-C expression (P = 0.031); in addition, VEGF-C expression was correlated with invasion of lymphatic vessels around the tumor (P = 0.004). Survival rates were significantly lower in patients in whom there was peritumor lymphatic vessel invasion (P < 0.001), extrapancreatic nerve plexus invasion (P = 0.001), and/or lymph node metastasis (P < 0.001). Based on these results, lymphatic invasion associated with adjacent tumor growth likely contributes to the development of metastatic tumors that invade the PNP.
癌细胞可以通过各种机制转移到全身，包括淋巴系统，导致肿瘤诱导的淋巴管生成，这可能会深刻影响患者的生存。本研究旨在研究淋巴管生成在胰腺癌转移到周围神经丛中的作用。免疫组织化学分析了 70 例导管腺癌患者的标本。使用的标志物包括淋巴管生成因子血管内皮生长因子（VEGF）-C、淋巴管特异性标志物 D2-40 和细胞角蛋白 19，这是胰腺肿瘤的独立预后因素。评估了生存率与淋巴管和胰周神经丛（PNP）侵袭之间的关系，发现癌组织附近的组织中淋巴管密度（LVD）明显升高。事实上，相邻组织中的 LVD 水平高于局限性癌组织，并且淋巴管侵入肿瘤附近组织与 PNP 侵袭（P = 0.005）和淋巴结转移（P = 0.010）显著相关。相应地，肿瘤周围组织的 LVD 与肿瘤周围淋巴管的侵袭（P = 0.024）和 VEGF-C 表达（P = 0.031）相关；此外，VEGF-C 表达与肿瘤周围淋巴管的侵袭相关（P = 0.004）。存在肿瘤周围淋巴管侵袭（P < 0.001）、胰外神经丛侵袭（P = 0.001）和/或淋巴结转移的患者的生存率显著降低（P < 0.001）。基于这些结果，与肿瘤相邻生长相关的淋巴侵袭可能导致侵袭 PNP 的转移性肿瘤的发展。
