A morphometric and immunohistochemical study on angiogenesis of human metastatic carcinomas of the liver



Background/Aims: To clarify the angiogenetic process and the origin of tumor vessels in human metastatic liver carcinomas. Methods: One hundred autopsy livers with metastatic carcinomas were studied by immunohistochemistry for von Willebrand factor, by lectin histochemistry for Ulex europaeus agglutinin I (UEA-I), and by morphometry of the density of tumor vessels in the liver metastases. In addition, tumor vessels were observed three-dimensionally in silicone rubber-injected livers with metastases. Results: Tumor vessels in metastatic liver carcinomas were positive for von Willebrand factor and UAE-I agglutinin I receptor. Tumor vessels first appeared in liver metastases of 200 μm in diameter. The density of the tumor vessels in the metastases increased up to 3mm in diameter, and it remained stable over 3mm. Sinusoidal endothelial cells around the liver metastases were positive for these endothelial markers. Sinusoidal endothelial cells were frequently in continuity with vessels in the metastases. Silicone rubber-injected specimens showed that blood vessels arising from surrounding sinusoids entered into the metastases. Conclusions: The angiogenesis of liver metastases may progress stepwise as the metastases enlarge, and capillarization of sinusoidal endothelium around the liver metastases may occur. Tumor vessels of liver metastases may in part originate from sinusoidal endothelial cells neighboring the tumors.