ALPHA-SMOOTH-MUSCLE ACTIN POSITIVE PERISINUSOIDAL STROMAL CELLS IN HUMAN HEPATOCELLULAR-CARCINOMA

The purpose of this study is to clarify the morphological characterist ics and functional significance of the perisinusoidal stromal cells in hepatocellular carcinoma. The liver specimens surgically resected fro m 24 patients with hepatocellular carcinoma were studied by electron m icroscopy and immunohistochemistry using monoclonal antibodies against a smooth muscle actin, vimentin and desmin. In the tissue space betwe en endothelial cells and trabeculae of cancer cells, the stromal cells were frequently found. They were strongly positive for alpha-smooth m uscle actin, weakly and less frequently positive for vimentin but nega tive for desmin. They varied in shape, size and distribution, stretchi ng cytoplasmic processes and occasionaIly surrounding the trabeculae o f cancer cells. They contained considerable amounts of microfilaments that were positive for alpha-smooth muscle actin and condensed in cell periphery. Along the cell membrane, the short dense areas and pinocyt otic vesicles were seen. The external lamina incompletely invested the stromal cells. They were always surrounded by amorphous material. In the granulation tissue and fibrotic areas around necrotic cancer tissu e, they were increased in size and number. On the other hand, immunohi stochemically and ultrastructurally, they closely resembled the Ito ce lls in the piecemeal necrosis that showed myofibroblastic transformati on. These results suggest that the perisinusoidal stromal cells in non necrotic cancer tissue produce the extracellular matrix in the tissue space and maintain the cancerous trabecular structure. After necrosis of cancer tissue, they may become activated and actively participate i n the fibrosis.