Extinction of FOXL2 expression in aggressive ovarian granulosa cell tumors in children.
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.
Kalfa
Nicolas
N
Unité d'Endocrinologie-Gynécologie Pédiatrique, Service de Pédiatrie 1, Hôpital Arnaud-de-Villeneuve, Montpellier, France.
Philibert
Pascal
P
Patte
Catherine
C
Ecochard
Aude
A
Duvillard
Pierre
P
Baldet
Pierre
P
Jaubert
Francis
F
Fellous
Marc
M
Sultan
Charles
C
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
C421604:FOXL2 protein, human; C085126:FOXO1 protein, human; D000074842:Forkhead Box Protein L2; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors