Expression of CD44, Vascular Endothelial Growth Factor, and Proliferating Cell Nuclear Antigen in Severe Venous Invasional Colorectal Cancer and Its Relationship to Liver Metastasis

Abstract: The first step in liver metastasis is venous invasion by cancer cells from the primary tumor. However, even among cases where the histology shows extensive venous invasion by the primary tumor, we sometimes find cases without synchronous liver metastases. As a result, there is a strong possibility that, besides the established causes of colorectal cancer and that of cancer cells invading the veins, some other important causes for liver metastasis must exist. We investigated the expression rates of CD44, proliferating cell nuclear antigen (PCNA), and vascular endothelial growth factor (VEGF) in 28 primary colorectal tumors using immunohistological techniques, and examined an association with liver metastasis. Cases that are strongly positive for CD44 or PCNA have a higher rate of synchronous liver metastases than cases with either no expression or a low expression. We could find no correlation between the VEGF expression and synchronous liver metastasis. In cases with severe venous invasion, VEGF is not correlated with liver metastasis whereas CD44 and PCNA are correlated with liver metastasis. In cases where severe venous invasion is histologically observed, an immunohistochemical analysis for CD44 and PCNA should be done to assess the likelihood of liver metastases.