In vivo expression of soluble Fas and Fap-1: Possible mechanisms of Fas resistance in human hepatoblastomas

Many tumour cells express both Fas and its ligand (FasL) on their surface a nd it has remained a mystery why such cells do not simply kill themselves. It remains to be determined whether Fas and Past are expressed in human hep atoblastomas and if so, what is responsible for the possible Fas resistance of these tumours. Tn this study, the expression of Fas and Past was examin ed in 23 cases of human hepatoblastoma by immunohistochemical staining. To elucidate possible Fas resistance in hepatoblastomas, Fas-resistance pathwa ys including the expression of bcl-2 and Fas-associated phosphatase-1 (FAP- 1), and the expression of soluble Fas (sFas) mRNA, were analysed by immunoh istochemistry and in situ reverse transcription-polymerase chain reaction ( in situ RT-PCR). Fas gene mutation in the death domain was also examined. P as and Past were expressed in all hepatoblastomas analysed. Twenty (87 per cent) and 18 (78 per cent) cases of hepatoblastoma were positive for sFas m RNA and FAP-1, respectively, but none of the hepatoblastomas expressed bcl- 2. Mutation in the death domain of the Fas gene was not found in hepatoblas tomas. Taken together, these findings demonstrated that Fas, a death recept or, and its ligand are co-expressed in hepatoblastomas in vivo, but some in hibitors of Fas-mediated apoptosis are also expressed in these tumours. The se results suggest that it is probably due to the action of inhibitory mole cules of the Fas pathway that the tumour cells of hepatoblastomas do not hi ll themselves in an autocrine-driven cycle and that in this manner hepatobl astomas avoid apoptosis. Copyright (C) 1999 John Wiley & Sons, Ltd.