Aberrant expression of ovary determining gene FOXL2 in the testis and juvenile granulosa cell tumor in children

Unité d'Endocrinologie-Gynécologie Pédiatrique, Service de Pédiatrie 1, Hôpital Arnaud-de-Villeneuve and Service d'Hormonologie du Développement et de Reproduction, Hôpital Lapeyronie, Centre Hospitalier Universitaire Montpellier, Montpellier, France.
The Journal of urology (Impact Factor: 3.75). 09/2008; 180(4 Suppl):1810-3. DOI: 10.1016/j.juro.2008.03.097
Source: PubMed

ABSTRACT FOXL2 is the earliest known marker of ovarian differentiation in mammals. It is involved in ovarian somatic cell differentiation and further follicle maintenance. FOXL2 is not implicated in determination of the male gonad and it is absent in the testis. We investigated whether the rare JGCTT (juvenile granulose cell tumor of the testis), named for its histological similarity to ovarian tumor, could be the first illustration of aberrant expression of this ovary determining gene in the human testis.
Between 1990 and 2004, 3 boys with JGCTT were reported from the TGM95 database of the French Society for Childhood Cancer and from 8 pediatric endocrinology centers. Orchiectomy was performed in these patients. Immunohistochemistry of FOXL2, and co-immunofluorescence of FOXL2 and SOX9 were performed on tumor sections.
Testicular tumor cells showed aberrant expression of FOXL2, which resembled normal ovarian granulosa cells. The localization of FOXL2 expression was nuclear without any cytoplasmic sequestration, suggesting that FOXL2 had biological activity. Conversely SOX9, which is present in the nucleus of normal testicular cells, was sequestered in the cytoplasm of granulosa tumor cells or markedly under expressed in the nuclei. In this case of residual SOX9 nuclear expression the expression of FOXL2 and SOX9 was mutually exclusive.
To our knowledge we report the first human model of aberrant intratesticular expression of an ovary determining gene along with the extinction of SOX9 and the transdifferentiation of a testicular cell into a granulosa tumor cell.

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