Department of Surgery, The University of Melbourne, Austin Hospital, Melbourne, Victoria, Australia.
J Surg Res. 2012 Apr;173(2):292-8. doi: 10.1016/j.jss.2010.09.012. Epub 2010 Oct 8.
Hematogenous spread is considered the predominant pathway for development of colorectal liver metastases (CRLM) and subsequent further tumor dissemination portal nodal involvement is also frequently observed in such cases, suggesting that lymphatics may have a role in the spread of CRLM. The role of lymphatics in the development of liver metastases is, however, controversial. The lymphatic patterns of CRLM were determined using a well established murine model.
CRLM were induced using a well established murine intrasplenic colorectal cancer model. Tumors were assessed at varying stages of development, and lymphatic patterns were determined in tumors and liver by immunohistochemistry staining for podoplanin and LYVE-1. Blood vessels were characterized using the vascular marker CD-34. Assessment was undertaken using digital microscopy and image analysis.
Peri- and intratumoral lymphatic vessels were identified by podoplanin staining in all metastases and significantly increased with tumor growth. LYVE-1 staining was also noted but was variable. There was a concurrent significant increase in portal lymphatic staining within the normal liver with increasing growth of CRLM.
There is increased expression of lymphatics within CRLM and normal liver with increasing tumor growth. Lymphatic development is likely to play a significant role in the intrahepatic and periportal dissemination of CRLM.
血行播散被认为是结直肠癌肝转移（CRLM）发展的主要途径，在这种情况下，门静脉淋巴结受累也很常见，这表明淋巴可能在 CRLM 的扩散中起作用。然而，淋巴在肝转移发展中的作用存在争议。使用成熟的小鼠模型确定了 CRLM 的淋巴模式。
使用成熟的小鼠脾内结直肠癌模型诱导 CRLM。在肿瘤发展的不同阶段评估肿瘤，并通过对足突蛋白和 LYVE-1 的免疫组织化学染色来确定肿瘤和肝脏中的淋巴模式。使用血管标志物 CD-34 对血管进行特征描述。使用数字显微镜和图像分析进行评估。
所有转移瘤中均通过 podoplanin 染色识别出肿瘤周围和肿瘤内的淋巴管，并且随着肿瘤的生长显著增加。LYVE-1 染色也被注意到，但存在变异性。随着 CRLM 生长的增加，正常肝脏内门静脉的淋巴染色也同时显著增加。
随着肿瘤生长，CRLM 和正常肝脏中的淋巴管表达增加。淋巴的发展可能在 CRLM 的肝内和门周播散中起重要作用。
