Lymphatic Patterns of Colorectal Liver Metastases

Abstract

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.