Aberrant expression of ovary determining gene FOXL2 in the testis and juvenile granulosa cell tumor in children.

Abstract

PURPOSE:

FOXL2 is the earliest known marker of ovarian differentiation in mammals. It is involved in ovarian somatic cell differentiation and further follicle maintenance. FOXL2 is not implicated in determination of the male gonad and it is absent in the testis. We investigated whether the rare JGCTT (juvenile granulose cell tumor of the testis), named for its histological similarity to ovarian tumor, could be the first illustration of aberrant expression of this ovary determining gene in the human testis.

MATERIALS AND METHODS:

Between 1990 and 2004, 3 boys with JGCTT were reported from the TGM95 database of the French Society for Childhood Cancer and from 8 pediatric endocrinology centers. Orchiectomy was performed in these patients. Immunohistochemistry of FOXL2, and co-immunofluorescence of FOXL2 and SOX9 were performed on tumor sections.

RESULTS:

Testicular tumor cells showed aberrant expression of FOXL2, which resembled normal ovarian granulosa cells. The localization of FOXL2 expression was nuclear without any cytoplasmic sequestration, suggesting that FOXL2 had biological activity. Conversely SOX9, which is present in the nucleus of normal testicular cells, was sequestered in the cytoplasm of granulosa tumor cells or markedly under expressed in the nuclei. In this case of residual SOX9 nuclear expression the expression of FOXL2 and SOX9 was mutually exclusive.

CONCLUSIONS:

To our knowledge we report the first human model of aberrant intratesticular expression of an ovary determining gene along with the extinction of SOX9 and the transdifferentiation of a testicular cell into a granulosa tumor cell.

• Authors: Nicolas Kalfa, Marc Fellous, Brigitte Boizet-Bonhoure, Catherine Patte, Pierre Duvillard, Catherine Pienkowski, Francis Jaubert, Aude Ecochard, Charles Sultan
• Journal: The Journal of urology (J Urol) Vol. 180 Issue 4 Suppl Pg. 1810-3 (Oct 2008) ISSN: 1527-3792 [Electronic] United States
• PMID: 18721930 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• FOXL2 protein, human
• Forkhead Box Protein L2
• Forkhead Transcription Factors
• High Mobility Group Proteins
• SOX9 Transcription Factor
• SOX9 protein, human
• Transcription Factors

Topics

• Cell Differentiation (physiology)
• Forkhead Box Protein L2
• Forkhead Transcription Factors (metabolism)
• Gene Expression Regulation, Neoplastic
• Granulosa Cell Tumor (chemistry, metabolism)
• High Mobility Group Proteins (metabolism)
• Humans
• Immunohistochemistry
• Male
• SOX9 Transcription Factor
• Testicular Neoplasms (chemistry, metabolism)
• Testis (metabolism)
• Transcription Factors (metabolism)