title: GATA-4 and FOG-2 expression in pediatric ovarian sex cord-stromal tumors replicates embryonal gonadal phenotype: results from the TREP project.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Pediatric Surgery, Departments of Pediatrics and Gynaecology-Obstetrics, University Hospital, Padua, Italy. calogero.virgone@unipd.it
authors.forename: Calogero
authors.initials: C
authors.lastname: Virgone
authors.forename: Giovanni
authors.initials: G
authors.lastname: Cecchetto
authors.forename: Andrea
authors.initials: A
authors.lastname: Ferrari
authors.forename: Gianni
authors.initials: G
authors.lastname: Bisogno
authors.forename: Vittoria
authors.initials: V
authors.lastname: Donofrio
authors.forename: Renata
authors.initials: R
authors.lastname: Boldrini
authors.forename: Paola
authors.initials: P
authors.lastname: Collini
authors.forename: Patrizia
authors.initials: P
authors.lastname: Dall'Igna
authors.forename: Rita
authors.initials: R
authors.lastname: Alaggio
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005260:Female; D050991:GATA4 Transcription Factor / Q000378:metabolism*; D006801:Humans; D007223:Infant; D007265:Inhibins / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000473:pathology; D010053:Ovary / Q000378:metabolism / Q000473:pathology; D010641:Phenotype; D018312:Sex Cord-Gonadal Stromal Tumors / Q000378:metabolism* / Q000473:pathology; D014157:Transcription Factors / Q000378:metabolism*; D014746:Vimentin / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D050991:GATA4 Transcription Factor; C484170:GATA4 protein, human; D014157:Transcription Factors; D014746:Vimentin; C117427:ZFPM2 protein, human; D007265:Inhibins