Extinction of FOXL2 expression in aggressive ovarian granulosa cell tumors in children

• Published in: Fertility and sterility Vol. 87; no. 4; pp. 896 - 901
• Main Authors: Kalfa, Nicolas, M.D, Philibert, Pascal, Pharm.D, Patte, Catherine, M.D, Ecochard, Aude, M.D, Duvillard, Pierre, M.D., Ph.D, Baldet, Pierre, M.D., Ph.D, Jaubert, Francis, M.D., Ph.D, Fellous, Marc, M.D., Ph.D, Sultan, Charles, M.D., Ph.D
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.04.2007; Elsevier Science
• Subjects: Adolescent; Biological and medical sciences; Child; Child, Preschool; Female; Female genital diseases; Forkhead Box Protein L2; Forkhead Box Protein O1; Forkhead Transcription Factors - analysis; Forkhead Transcription Factors - genetics; Forkhead Transcription Factors - physiology; granulosa cell tumor; Granulosa Cell Tumor - chemistry; Granulosa Cell Tumor - pathology; Granulosa Cell Tumor - therapy; Granulosa Cells - pathology; Gynecology. Andrology. Obstetrics; human FOXL2 protein; Humans; Immunohistochemistry; Infant; Internal Medicine; Medical sciences; Neoplasm Staging; Obstetrics and Gynecology; Ovarian neoplasms; Ovarian Neoplasms - chemistry; Ovarian Neoplasms - pathology; Ovarian Neoplasms - therapy; Prognosis; Retrospective Studies; Tumors; granulosa cell tumor; human FOXL2 protein; Ovarian neoplasms; prognosis; child; Human; Prognosis; Protein; Female genital diseases; Ovarian diseases; Granulosa cell; Fertility; Child; Tumor cell; High malignancy; Ovarian tumor
• ISSN: 0015-0282; 1556-5653
• DOI: 10.1016/j.fertnstert.2006.11.016

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). Design Nationwide retrospective study. Setting University Hospital of Montpellier, Department of Hormonology. Patient(s) 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. Intervention(s) Immunohistochemistry studies of FOXL2 on OGCT slides. Main Outcome Measure(s) Level of FOXL2 expression within the tumor, International Federation of Gynecology and Obstetrics classification, and tumor recurrences. Result(s) 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). Conclusion(s) 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.