[1766] GATA-4 and FOG-2 Expression in Pediatric Ovarian Sex Cord-Stromal Tumors (SCST): An Italian Multi-Institutional Cooperative Study

C Virgone, G Cecchetto, G Bisogno, P Dall'Igna, V D'Onofrio, R Boldrini, P Collini, R Alaggio. University of Padova, Padova, Italy; Ospedale Pausilipon, Napoli, Italy; Ospedale B. Gesù, Roma, Italy; Istituto Nazionale Tumori, Milano, Italy

Background: GATA-4 is a transcription factor regulating cell differentiation and proliferation: in the ovary it controls the expression of α-inhibin and anti-Müllerian Hormone (MIH). FOG-2 activates or inhibits the transcriptional activity of GATA-4, counteracting the trans-activation of the MIH gene by GATA-4 in fetal ovary. A prognostic role of GATA-4 in adult ovarian Granulosa Cell Tumor has been reported. Pediatric SCST are less than 8-10% of all ovarian tumors, with the most frequent histotypes represented by Juvenile Granulosa Cell Tumors (JGCT) and Sertoli-Leydig Cell tumors (SLCT). We explored the potential pathogenetic and prognostic role of FOG-2 and GATA-4 in pediatric SCST.
Design: Histological slides from 15 SCST entered into TREP-study (an Italian multi-institutional study for rare tumors) were reviewed, and immunostains for GATA-4, FOG-2 and α-inhibin were performed. Clinical information were retrieved from TREP files.
Results: Clinico-pathologic features are summarized in the table. Mean age was 112 months (range 7-224); 1 tumor was bilateral, 12 were stage I, 2 stage II, 1 was metastatic at diagnosis. Mean follow-up was 26 months.

Table 1
6 JGCT5/61/53/66 I CR
6 SLCT4*/62/45/64 I CR, 1 II CR(after metachronous ovarian tumor), 1DOD
FT/SST2/31/10/33 I CR
*only Sertoli component. Legend: I/IICR=first/second complete remission, DOD=died of disease

All were treated by surgery, with adjuvant chemotherapy in 3. There were 6 JGCT, 6 SLCT, 2 Fibroma/Thecoma (FT) and 1 Sclerosing Stromal Tumor (SST). SLCT behaved more aggressively: 1 SLCT (FOG/GATA negative) was metastatic at diagnosis, and the patient is in I CR; one poorly differentiated SLCT with fatal outcome and 1 metachronous bilateral SLCT were GATA-4 and/or FOG2 positive.
Conclusions: Compared to adult GCT, JGCT express FOG-2, but are frequently GATA-4 negative, suggesting a possible switch to the phenotype of the fetal ovary. The favourable prognosis in most pediatric SCST does not allow to draw a conclusion on the prognostic role of FOG-2 and GATA-4. Therefore, absence of GATA-4 in JGCT may contribute to their favourable prognosis. In SLCT, GATA-4 and/or FOG-2 were expressed in more aggressive tumors. There was no relationship between FOG-2/GATA-4 and α-inhibin staining.
Category: Pediatrics

Monday, March 22, 2010 11:15 AM

Platform Session: Section H 2, Monday Morning


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