METASTATIC MODELS OF HUMAN LIVER-CANCER IN NUDE-MICE ORTHOTOPICALLY CONSTRUCTED BY USING HISTOLOGICALLY INTACT PATIENT SPECIMENS

In this study of orthotopic implantation of histologically intact surg ical specimens, the authors constructed metastatic models of human hep atocellular carcinoma (HCC) in nude mice. Histologically intact human liver cancer specimens, derived from patients, were implanted directly into the liver of nude mice, and their orthotopic growth and metastas es were observed. The transplantability and metastatic rate of two spe cimen groups (primary and metastatic lesions) were analysed. a-Fetopro tein (AFP) was also determined in transplanted tumours by an immunohis tochemical method. Orthotopic growth was observed in 14 of 30 transpla nted specimens and formation of metastases in 7 cases, which exhibited the variety of clinical behaviours seen in patients with HCC. These b ehaviours included local growth, regional invasion, spontaneous intrah epatic, lymph node and lung metastasis and peritoneal seeding. In two groups the growth rate of metastatic lesions following implantation wa s clearly higher than that of primary tumours. Chromosome analysis fro m locally growing tumours confirmed their morphologically human origin . An immunohistochemical study showed that implanted tumours originati ng from AFP-positive specimens maintained AFP expression. These result s indicated that the animal models should prove valuable for developin g new treatment modalities and studying the mechanism of metastasis of human HCC.