EVIDENCE THAT MYOFIBROBLAST-LIKE CELLS ARE THE CELLULAR SOURCE OF CAPSULAR COLLAGEN IN HEPATOCELLULAR-CARCINOMA

Background/Aims: The prognosis for patients with hepatocellular carcin oma is poor although tumour encapsulation has been associated with imp roved survival and disease-free rates, While the source of the tumour capsule is unclear, the major role that activated hepatic stellate cel ls play in the deposition of liver matrix in normal and diseased state s suggests the possible involvement of these cells in tumour encapsula tion, Methods: Twenty-four liver tumours (seven encapsulated HCC, seve n non-encapsulated HCC, 10 colorectal metastases) were studied, Activa ted hepatic stellate cells were identified by immunohistochemistry for alpha-smooth muscle actin (alpha-SMA) and in situ hybridization for p ro-collagen alpha(1) (I) mRNA, Collagen deposition was localized using Masson's trichrome stain, Results: Pro-collagen alpha(1) (I) mRNA co- localized to alpha-SMA positive hepatic stellate cells within the regi on of increased collagen deposition in (i) the tumour capsule of encap sulated HCC, and (ii) the tumour junction of non-encapsulated HCC and colorectal metastasis, In addition, there was marked peritumour expres sion of alpha-SMA and procollagen alpha(1) (I) mRNA, which diminished with distance away from the tumour in all tumour groups, The degree of expression was greatest with encapsulated HCC, less with non-encapsul ated HCC and least with colorectal metastasis, This contrasted with th e absence of alpha-SMA expression in normal liver from the same patien ts, Within the tumours, colorectal metastases differed from HCC by dem onstrating marked alpha-SMA expression and collagen deposition in the septa, Conclusions: Our findings demonstrate that activated hepatic st ellate cells (i) are responsible for increased peritumour collagen pro duction in non-encapsulated HCC and colorectal metastasis, and (ii) ma y be implicated in tumour capsule formation in HCC and metastasis stro ma development, Thus, stellate cells may influence the local hepatic i nvasion by these tumours.