Pediatric Surgery, Departments of Pediatrics and Gynaecology-Obstetrics, University Hospital, Padua, Italy.
PLoS One. 2012;7(9):e45914. doi: 10.1371/journal.pone.0045914. Epub 2012 Sep 24.
GATA proteins are a family of zinc finger transcription factors regulating gene expression, differentiation and proliferation in various tissues. The expression of GATA-4 and FOG-2, one of its modulators, was studied in pediatric Sex Cord-Stromal tumors of the ovary, in order to evaluate their potential role as diagnostic markers and prognostic factors.
Clinical and histological data of 15 patients, enrolled into the TREP Project since 2000 were evaluated. When available, immunostaines for FOG-2, GATA-4, α-Inhibin, Vimentin and Pancytokeratin were also analyzed.
In our series there were 6 Juvenile Granulosa Cell Tumors (JGCT), 6 Sertoli-Leydig Cell Tumors (SLCT), 1 Cellular Fibroma, 1 Theca Cell Tumor and 1 Stromal Sclerosing Tumor (SST). Thirteen patients obtained a complete remission (CR), 1 reached a second CR after the removal of a metachronous tumor and 1 died of disease. Inhibin was detectable in 11/15, Vimentin in 13/15, Pancytokeratin in 6/15, GATA-4 in 5/13 and FOG-2 in 11/15. FOG-2 was highly expressed in 5/6 JGCT, while GATA-4 was weakly detectable only in 1 of the cases. SLCT expressed diffusely FOG-2 (4/6) and GATA-4 (3/5). GATA-4 and FOG-2 were detected in fibroma and thecoma but not in the SST.
Pediatric granulosa tumors appear to express a FOG-2/GATA-4 phenotype in keeping with primordial ovarian follicles. High expression of GATA-4 does not correlate with aggressive behaviour as seen in adults, but it is probably involved in cell proliferation its absence can be associated with the better outcome of JGCT. SLCTs replicate the phenotype of Sertoli cells during embryogenesis in normal testis. In this group, the lack of expression of FOG-2 in tumors in advanced stages might reveal a hypothetical role in inhibiting GATA-4 cell proliferation pathway. In fibroma/thecoma group GATA-4 and FOG-2 point out the abnormal activation of GATA pathway and might be involved in the onset of these tumors.
GATA 蛋白是一类锌指转录因子，可调节各种组织中的基因表达、分化和增殖。本研究旨在探讨其调节因子之一 FOG-2 的表达，以评估其作为诊断标志物和预后因素的潜在作用。
对 2000 年以来纳入 TREP 项目的 15 例患儿的临床和组织学资料进行评估。当有条件时，还分析了 FOG-2、GATA-4、α-抑制素、波形蛋白和细胞角蛋白的免疫组化染色。
本研究包括 6 例儿童颗粒细胞瘤（juvenile granulosa cell tumor，JGCT）、6 例儿童睾丸间质细胞瘤（Sertoli-Leydig cell tumor，SLCT）、1 例纤维瘤、1 例卵巢门细胞瘤和 1 例间质硬化性肿瘤（stromal sclerosing tumor，SST）。13 例患儿获得完全缓解（complete remission，CR），1 例在切除同步肿瘤后获得二次 CR，1 例因疾病死亡。15 例患儿中 11 例可检测到抑制素，13 例可检测到波形蛋白，6 例可检测到细胞角蛋白，13 例中 5 例可检测到 GATA-4，11 例中 5 例可检测到 FOG-2。5/6 例 JGCT 中高表达 FOG-2，而 GATA-4 仅在 1 例中弱阳性表达。6 例 SLCT 中弥漫表达 FOG-2（4/6）和 GATA-4（3/5）。纤维瘤和卵巢门细胞瘤中均表达 GATA-4 和 FOG-2，但 SST 中不表达。
儿童颗粒细胞瘤似乎表达与原始卵泡一致的 FOG-2/GATA-4 表型。GATA-4 的高表达与成人中所见的侵袭性行为无关，但可能与细胞增殖有关，其缺失可能与 JGCT 较好的预后相关。SLCT 复制了正常睾丸中胚胎期 Sertoli 细胞的表型。在这组中，晚期肿瘤中 FOG-2 的缺失可能提示其在抑制 GATA-4 细胞增殖途径中具有潜在作用。在纤维瘤/卵巢门细胞瘤组中，GATA-4 和 FOG-2 提示 GATA 途径的异常激活，可能与这些肿瘤的发生有关。
