p16(INK4A) - alterations in primary angiosarcoma of the liver

Background/Aims: Alterations in the p16 (CDKN2/MTS-1/INK4A) gene have been implicated in the tumorigenesis of different human cancers, Recent evidence shows that transcriptional silencing as a consequence of hypermethylation of CPG islands is the predominant mechanism of p16INK4a gene inactivation i n malignant epithelial tumors; This study was performed to determine whethe r alterations of p16 are involved in the development of angiosarcoma of the liver, Methods: The status of p16 was evaluated in 17 angiosarcomas of the liver b y methylation-specific PCR (MSP), microsatellite analysis, DNA sequencing a nd immunohistochemical staining. The results obtained were correlated with histopathological variables and with patient survival. Results: Hypermethylation of the 5 ' CPG island of the p16 gene was found i n 12 out of 17 (71%) angiosarcomas examined. Homozygous deletion at the p16 region was present in one case (6%), and loss of heterozygosity was presen t in two cases (12%). We failed to detect p16 gene missense mutations, The status of p16 correlated with neither histopathological factors nor with th e prognosis of the patients with angiosarcomas, Conclusions: These data suggest that inactivation of the p16 gene is a freq uent event in angiosarcomas of the liver. The most common somatic alteratio n is promotor methylation of the p16 gene. We failed to establish p16 as in dependent prognostic, factors in these tumors. (C) 2001 European Associatio n for the Study of the Liver. Published by Elsevier Science B.V. All rights reserved.