Role of myofibroblasts in tumour encapsulation of hepatocellular carcinomain haemochromatosis

Background/Aims: Hepatocellular carcinoma is a carcinoma malignancy and a m ajor complication of untreated haemochromatosis. Encapsulation of liver tum ours has been associated with a better prognosis and longer disease-free pe riods following resection, This study investigated the source of the tumour capsule in patients with haemochromatosis and coexisting hepatocellular ca rcinoma and examined potential factors influencing development. Methods: Fi ve haemochromatosis patients with encapsulated hepatocellular carcinoma wer e studied. Myofibroblasts were identified using combined immunohistochemist ry and in situ hybridisation for a-smooth muscle actin and procollagen alph a (1)(I) mRNA, respectively. Immunohistochemistry was also performed for tr ansforming growth factor (TGF)-beta (1), platelet-derived growth factor (PD GF)-beta receptor and malondialdehyde. Results. Procollagen alpha (1)(I) mR NA co-localised to alpha -smooth muscle actin positive myofibroblasts. The number of myofibroblasts was maximal within the capsule and decreased away from the tumour. TGF-beta (1) protein was expressed in iron-loaded cells in non-tumour liver at the interface of tumour capsule. PDGF-beta receptor ex pression was observed in mesenchymal cells in the tumour capsule and in por tal tracts. Malondialdehyde adducts were observed in the tumour, non-tumour tissue and in the capsule. Conclusions: This study provides evidence that myofibroblasts are the cell type responsible for collagen production within the tumour capsule surrounding hepatocellular carcinoma in haemochromatosi s, The production of TGF-beta (1) by iron-loaded hepatic cells at the tumou r capsule interface may perpetuate the myofibroblastic phenotype, resulting in, the formation of the tumour capsule.