title: Unusual virilization in girls with juvenile granulosa cell tumors of the ovary is related to intratumoral aromatase deficiency.
abstract: BACKGROUND
  Hyperandrogenism is a rare symptom of juvenile ovarian granulosa cell- tumors (JGCTO). This study aimed to determine whether hyperandrogenism was related to overexpression of SOX9, decreased expression of FOXL2 or absent aromatase expression in tumor with particular scheme of expression of P450scc and P450c17alpha.
  
  
  METHODS
  Through a nationwide study including the French Society of Pediatric Oncology, 6/30 patients with JGCTO presented with clinical hyperandrogenism and high plasma testosterone. Tumor specimens underwent immunofluorescence (SOX9, FOXL2) and immunochemistry (aromatase, P450scc, P450c17alpha). Results were compared with patients without hyperandrogenism.
  
  
  RESULTS
  SOX9 was expressed in the granulosa cell nucleus in 2/6 cases but also in 9/24 tumors without hyperandrogenism (p=n.s.). FOXL2 was absent or decreased in 3/6 cases of JGCTO with hyperandrogenism with no statistical difference from the group without this symptom. In 6/6 patients, the intratumoral expression of aromatase was absent (n=5) or dramatically reduced (n=1). In contrast, 15/24 patients without virilization exhibited conserved aromatase expression in their tumor (p<0.05). A variable number of tumoral cells expressed P450scc while some interstitial cells were focally immunopositive for P450c17alpha.
  
  
  CONCLUSIONS
  Unusual virilization in girls with JGCTO is not explained by a dysregulation in SOX9 or FOXL2 expression, but is related to a localized defect of aromatase expression in granulosa cells and to the ability of interstitial cells to produce testosterone.
authors.affiliation: Service d'Hormonologie du Développement et de la Reproduction, Hôpital Lapeyronie, CHU Montpellier, Montpellier, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Kalfa
authors.forename: Geri
authors.initials: G
authors.lastname: Méduri
authors.forename: Pascal
authors.initials: P
authors.lastname: Philibert
authors.forename: Catherine
authors.initials: C
authors.lastname: Patte
authors.forename: Brigitte
authors.initials: B
authors.lastname: Boizet-Bonhoure
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Thibaut
authors.forename: Catherine
authors.initials: C
authors.lastname: Pienkowski
authors.forename: Francis
authors.initials: F
authors.lastname: Jaubert
authors.forename: Micheline
authors.initials: M
authors.lastname: Misrahi
authors.forename: Charles
authors.initials: C
authors.lastname: Sultan
mesh_terms: D001141:Aromatase / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D005260:Female; D000074842:Forkhead Box Protein L2; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D006106:Granulosa Cell Tumor / Q000201:enzymology / Q000235:genetics / Q000473:pathology*; D006801:Humans; D017588:Hyperandrogenism / Q000201:enzymology / Q000235:genetics / Q000473:pathology*; D007150:Immunohistochemistry; D008856:Microscopy, Fluorescence; D010051:Ovarian Neoplasms / Q000201:enzymology / Q000235:genetics / Q000473:pathology*; D012189:Retrospective Studies; D055758:SOX9 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D013254:Steroid 17-alpha-Hydroxylase / Q000378:metabolism; D014770:Virilism / Q000378:metabolism
chemical_list: C421604:FOXL2 protein, human; D000074842:Forkhead Box Protein L2; D051858:Forkhead Transcription Factors; D055758:SOX9 Transcription Factor; C527932:SOX9 protein, human; D001141:Aromatase; C501892:CYP17A1 protein, human; D013254:Steroid 17-alpha-Hydroxylase