Buell-Gutbrod Rebecca, Ivanovic Marina, Montag Anthony, Lengyel Ernst, Fadare Oluwole, Gwin Katja
Department of Pathology, University of Chicago, Chicago, IL, USA.
Pediatr Dev Pathol. 2011 Sep-Oct;14(5):391-5. doi: 10.2350/10-12-0943-OA.1. Epub 2011 Jun 17.
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.
性腺母细胞瘤是一种混合性生殖细胞性索间质肿瘤，发生于发育异常的性腺，由未成熟生殖细胞和分化不定的性索间质细胞组成。FOXL2是女性性腺发育中最早表达的基因之一，在卵泡发生过程中，它是颗粒细胞正常分化所必需的。SOX9是Y染色体性别决定区域基因SRY的下游靶点，是睾丸发育以及（前）支持细胞形成和维持所必需的。本研究通过评估这些相互拮抗的转录因子的表达，对性腺母细胞瘤的性索间质细胞进行了特征分析。通过免疫组织化学检测了7例性腺母细胞瘤存档石蜡包埋材料中FOXL2和SOX9的表达及定位，其中5例被无性细胞瘤过度生长。性索间质细胞FOXL2呈强核染色，SOX9表达阴性。性腺母细胞瘤和无性细胞瘤成分中的生殖细胞未显示FOXL2和SOX9表达。性腺母细胞瘤和无性细胞瘤之间的过渡区域可见巢状结构，FOXL2表达逐渐减少。我们的结果支持性腺母细胞瘤的性索间质细胞成分起源于颗粒细胞的假说。此外，FOXL2似乎是评估无性细胞瘤过度生长和识别“原位无性细胞瘤”过渡区的有用标志物。由于FOXL2和SOX9表达不同，它们也有助于将性腺母细胞瘤与小管内生殖细胞肿瘤区分开来，并有助于区分具有支持细胞成分的肿瘤与具有颗粒细胞成分的性腺母细胞瘤。
