Chromosome Y-linked Testis Specific Protein Is Chracteristically Present in Gonadoblastoma
JD Hertel, PC Huettner, LP Dehner, JD Pfeifer. Washington University School of Medicine, St Louis, MO
Background: Gonadoblastoma (GB) is a rare gonadal neoplasm that usually occurs in intersex disorders including androgen insensitivy syndrome, mixed gonadal dysgenisis, Turner syndrome, and Turner syndrome mosaicism. The vast majority of GB develop in the setting of an abnormal karyotype with at least a portion of the Y chromosome present, a finding that led to the hypothesis of the existence of a gonadoblastoma locus (GBY) that is critical to the development of GB. The portion of the Y chromosome conserved in GB has been mapped to the centromeric portion of the short arm of the Y chromosome. While a number genes are present in this region, several factors have implicated the testis specific protein, Y-linked (TSPY) gene in the pathogenesis of GB. First, by immunohistochemistry TSPY has been noted to be over expressed in GB. Second, though the function of the TSPY protein is unknown, it appears to be involved in cell cycle regulation. TSPY has a high degree of homology with the cyclin B family of proteins that regulate the cell cycle. Third, in vitro experiments have suggested that expression of the TSPY may transition cells through the G(2)/M phase of the cell cycle.
Design: Six cases of GB were identified from our files dating back to 1989. A series of overlapping fluorescent in situ hybridization (FISH) probes designed to target approximately 450 kb of the GBY locus including TSPY1 was developed from human BAC clones. A commercially available chromosome X CEP probe was used to identify the X chromosome. Dual color FISH using both probes simultaneously was used to evaluate cases for X and Y chromosomal DNA.
Results: FISH analysis demonstrated X and Y chromosomal DNA in five of six (84%) GB; in these five cases the adjacent noneoplastic ovary showed the same DNA pattern as the GB. In one of these cases an associated germ cell tumor showed the same DNA pattern as the GB. The GB that showed no Y chromosomal DNA arose in a Gravida 2 Para 2 woman with two X chromosomes; in this case the nonneoplastic ovary and an associated germ cell tumor showed the same DNA pattern as the GB.
Conclusions: FISH based testing for the GBY locus, specifically the TSPY gene, can aid in the detection of intersex disorders in women who develop GB. Our demonstration of the lack of an identifiable GBY locus in a fertile woman, specifically TSPY gene, suggests that this Y chromosomal region is not necessary for the development of GB.
Monday, March 9, 2009 9:30 AM
Poster Session I Stowell-Orbison/Autopsy Award # 153, Monday Morning