title: Extinction of FOXL2 expression in aggressive ovarian granulosa cell tumors in children.
abstract: OBJECTIVE
  In the female gonad, FOXL2 is a key factor for proper differentiation of granulosa cells (GC) during folliculogenesis and its expression persists in the ovary after birth. The aim of this multicentric nationwide study was to determine whether FOXL2 expression varies during tumoral proliferation of GC cells in juvenile ovarian GC tumors (OGCT).
  
  
  METHODS
  Nationwide retrospective study.
  
  
  METHODS
  University Hospital of Montpellier, Department of Hormonology.
  
  
  METHODS
  Between 1994 and 2004, 26 patients with juvenile OGCT were reported in the TGM95 database of the French Society for Childhood Cancer (SFCE) and from eight pediatric endocrinology centers. Immunohistochemistry was performed using an anti-FOXL2 antibody.
  
  
  METHODS
  Immunohistochemistry studies of FOXL2 on OGCT slides.
  
  
  METHODS
  Level of FOXL2 expression within the tumor, International Federation of Gynecology and Obstetrics classification, and tumor recurrences.
  
  
  RESULTS
  FOXL2 expression was absent in the GC of 10 patients and was markedly reduced in the cells of 4 patients. Precocious pseudopuberty was more frequently the revealing symptom in the children with conserved FOXL2 expression. Patients with no or reduced expression of FOXL2 more frequently exhibited associated hemorrhagic ascites, higher mitotic activity in the tumor, and significantly more advanced oncologic staging. All patients requiring complementary treatment (n = 7; chemotherapy or complementary surgery) had reduced expression of FOXL2 in the tumor. All recurring OGCT exhibited a complete extinction of FOXL2 expression (n = 3).
  
  
  CONCLUSIONS
  These results show that FOXL2 is not expressed or is underexpressed in juvenile OGCT with an aggressive pattern of progression, and it thus may be a prognostic factor for these tumors.
authors: Unité d'Endocrinologie-Gynécologie Pédiatrique, Service de Pédiatrie 1, Hôpital Arnaud-de-Villeneuve, Montpellier, France.
authors: Nicolas
authors: N
authors: Kalfa
authors: Pascal
authors: P
authors: Philibert
authors: Catherine
authors: C
authors: Patte
authors: Aude
authors: A
authors: Ecochard
authors: Pierre
authors: P
authors: Duvillard
authors: Pierre
authors: P
authors: Baldet
authors: Francis
authors: F
authors: Jaubert
authors: Marc
authors: M
authors: Fellous
authors: Charles
authors: C
authors: Sultan
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D005260:Female; D000074842:Forkhead Box Protein L2; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors / Q000032:analysis* / Q000235:genetics / Q000502:physiology; D006106:Granulosa Cell Tumor / Q000737:chemistry* / Q000473:pathology / Q000628:therapy; D006107:Granulosa Cells / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000737:chemistry* / Q000473:pathology / Q000628:therapy; D011379:Prognosis; D012189:Retrospective Studies
chemical_list: C421604:FOXL2 protein, human; C085126:FOXO1 protein, human; D000074842:Forkhead Box Protein L2; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors