GONADOBLASTOMAS IN 45,X 46,XY MOSAICISM - ANALYSIS OF Y-CHROMOSOME DISTRIBUTION BY FLUORESCENCE IN-SITU HYBRIDIZATION/

Gonadoblastomas are composed of nests of neoplastic germ cells and sex cord derivatives surrounded by ovarian-type stroma. These tumors are found almost exclusively in persons with gonadal dysgenesis associated with a Y chromosome or Y chromosome fragment, and accordingly, the Y chromosome has been implicated in gonadoblastoma oncogenesis. To evalu ate this association, we used two-color fluorescence in situ hybridiza tion with chromosome-specific probes to determine the distribution of the X and Y chromosomes in the tumor nests and surrounding stromal cel ls in paraffin tissue sections of three gonadoblastomas in two patient s with gonadal dysgenesis and 45,X /46,XY mosaicism. Statistical analy sis of the data from the fluorescence in situ hybridization demonstrat ed that in all three gonadoblastomas, the proportion of nuclei with a Y chromosome signal was significantly higher in the tumor cells than i n the nontumoral cells of the surrounding stroma (P<.001). These resul ts suggest that Y chromosome material participates in gonadoblastoma t umorigenesis.