Liver metastases from colorectal adenocarcinomas grow in three patterns with different angiogenesis and desmoplasia

The liver is a highly vascularized organ which frequently hosts metastases in patients with colorectal adenocarcinomas. The hypothesis of this study i s that the hypoxic drive of angiogenesis might be minimal or absent in thos e growing liver metastases which are capable of preserving the stromal stru cture, including the numerous sinusoidal blood vessels. Representative para ffin sections of liver metastases from 26 patients with colorectal adenocar cinoma were investigated. Three different growth patterns were found. In th e desmoplastic and in the pushing growth patterns (42% and 46% of all metas tases, respectively), the architecture of the liver parenchyma was not pres erved. In the replacement growth pattern (12% of all cases), the reticulin pattern of the liver parenchyma was conserved within the metastases at the tumour-liver parenchyma interface. The endothelial cells of the blood vesse ls near the interface in the metastases of the replacement type did not exp ress CD34, nor were they surrounded by alpha-smooth muscle actin-positive m ural cells. In the desmoplastic and in the pushing growth patterns, 23% and 52% of all blood vessels in this area were covered by pericytes. The fract ion of proliferating endothelial cells was low in the metastases with a des moplastic or a replacement growth pattern (about 3%), compared with metasta ses with a pushing growth pattern (11%). Tumour cell apoptosis was highest in the pushing-type metastases and was inversely correlated with microvesse l density in liver metastases. The ratio of the proliferating tumour cell f raction and the proliferating endothelial cell fraction, roughly representi ng the degree of angiogenesis-dependent growth, was three- to four-fold hig her in the replacement-type metastases compared with the other metastases. In summary, the present study has demonstrated that liver metastases are a heterogeneous group, with different growth patterns which predict the fract ion of immature blood vessels, the fraction of proliferating endothelial ce lls, and the fraction of apoptotic tumour cells. The replacement growth pat tern expands with minimal angiogenesis by co-opting the stroma with the sin usoidal blood vessels of the liver. (C) Copyright 2001 John Wiley & Sons, L td.