Aims/methods: In the human liver, alpha-smooth muscle actin (ASMA) is present in smooth muscle of the vasculature, perisinusoidal cells (Ito cells), and myofibroblasts derived from perisinusoidal cells. In this study, we investigated ASMA-positive stromal cells and their relation to tumor fibrosis in 50 cholangiocarcinomas, 30 hepatocellular carcinomas, and 57 metastatic liver carcinomas.
Results: Tumor fibrosis was much more extensive in cholangiocarcinomas and metastatic liver carcinomas than in metastatic liver carcinomas. ASMA immunoreactivity was prominent in the sinusoids surrounding cancer nodules and in the cancerous stroma, not in sinusoids remote from cancer nodules. ASMA-positive stromal cells were divisible into peritumoral ASMA-positive perisinusoidal cells and intratumoral ASMA-positive stromal cells. Both types of ASMA-positive cells were abundant in cholangiocarcinomas and metastatic liver carcinomas, but much more scanty in hepatocellular carcinomas. The number of both types showed a significant positive correlation with the degree of tumor fibrosis. The peritumoral ASMA-positive perisinusoidal cells were frequently in direct continuity with intratumoral ASMA-positive stromal cells in cholangiocarcinomas and metastatic liver carcinomas.
Conclusions: These findings show that ASMA-positive stromal cells are related to tumor fibrosis in liver malignancies. Although direct evidence is lacking, the data suggest that, in cholangiocarcinomas and metastatic liver carcinomas, peritumoral ASMA-positive perisinusoidal cells transform into activated perisinusoidal cells (myofibroblasts), are incorporated into the tumor (intratumoral ASMA-positive stromal cells), and produce extracellular matrix proteins, that lead to tumor fibrosis. The scanty ASMA-positive cells in hepatocellular carcinomas may in part be responsible for the small amount of fibrosis in this tumor.