CLONAL ANALYSIS OF FOCAL NODULAR HYPERPLASIA OF THE LIVER

Recent evidence suggests that focal nodular hyperplasia of the liver ( FNH) may represent a hyperplastic response to a vascular malformation, but the precise etiology remains unclear. We performed a clonal analy sis of ten FNHs from wine patients by patterns of X chromosome inactiv ation, DNA isolated from paraffin-embedded specimens was subjected to polymerase chain reaction amplification for a highly polymorphic regio n of the human androgen receptor gene (HUMARA), Predigestion of tumor DNA with the methylation-sensitive, restriction enzyme HpaII allowed f or selective amplification of the methylated (inactivated) allele. Of the nine patients analyzed, seven were heterozygous for the HUMARA pol ymorphism and informative for analysis, One informative patient had tw o lesions, for a total of eight FNHs Amplification of lesional DNA aft er HpaII digestion demonstrated clonality in six of the eight informat ive cases. Paired tissue samples from different lesional areas were av ailable in four of the six FNHs with evidence of clonality, In three o f the four cases, DNA extracted from the two tissue samples showed bot h evidence of clonality and an identical pattern of X chromosome inact ivation. In the remaining case, one sample showed evidence of clonalit y whereas the other was nonclonal, Three hepatic adenomas from two inf ormative patients Were also analyzed for comparative purposes, aa of w hich showed evidence of clonality after HpaII digestion. The current s tudy illustrates that most cases of FNH show a uniform pattern of X ch romosome inactivation consistent with clonality.