FOXL2 and SOX9 distinguish the lineage of the sex cord-stromal cells in gonadoblastomas.

Rebecca Buell-Gutbrod, Marina Ivanovic, Anthony Montag, Ernst Lengyel, Oluwole Fadare, Katja Gwin

Department of Pathology, University of Chicago, Chicago, IL, USA.

Pediatric and developmental pathology : the official journal of the Society for Pediatric Pathology and the Paediatric Pathology Society 2011 Sep-Oct

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Gonadoblastomas are mixed germ cell sex cord-stromal tumors that arise in dysgenetic gonads and are composed of immature germ cells and sex cord-stromal cells of indeterminate differentiation. FOXL2 is one of the first genes expressed in female gonad development, and it is required for proper granulosa cell differentiation during folliculogenesis. SOX9 , a downstream target of SRY , the gene in the Y chromosomal sex-determining region, is required for testicular development and for the formation and maintenance of (pre-)Sertoli cells. This study characterized the sex cord-stromal cells of gonadoblastoma by evaluating the expression of these counteracting transcription factors. Archival paraffin-embedded material of 7 gonadoblastomas, 5 of which were overgrown by dysgerminoma, was examined by immunohistochemistry for expression and localization of FOXL2 and SOX9. The sex cord-stromal cells revealed strong nuclear staining for FOXL2 and were negative for SOX9 expression. Germ cells in the gonadoblastoma and dysgerminoma components showed no FOXL2 and SOX9 expression. Areas of transition between gonadoblastoma and dysgerminoma revealed nests with a gradual reduction of FOXL2 expression. Our results support the hypothesis that the sex cord-stromal cell component of gonadoblastomas is of granulosa cell origin. In addition, FOXL2 appears to be a useful marker for the evaluation of overgrowth by dysgerminomas and for the identification of the transition zone of "dysgerminoma in situ." As FOXL2 and SOX9 are differentially expressed, they also should be useful for distinguishing gonadoblastomas from intratubular germ cell neoplasias and can help to differentiate those with a Sertoli cell component from gonadoblastoma with a granulosa cell component.

Citation

Rebecca Buell-Gutbrod, Marina Ivanovic, Anthony Montag, Ernst Lengyel, Oluwole Fadare, Katja Gwin. FOXL2 and SOX9 distinguish the lineage of the sex cord-stromal cells in gonadoblastomas. Pediatric and developmental pathology : the official journal of the Society for Pediatric Pathology and the Paediatric Pathology Society. 2011 Sep-Oct;14(5):391-5