Transcription Factors GATA-4 and GATA-6, and their Potential Downstream Effectors in Ovarian Germ Cell Tumors

Abstract

Ovarian germ cell tumors (GCTs) are histologically heterogeneous neoplasms originating from activated germ cells, the oocyte stem cells. These rare tumors often contain many different tissues mixed together, and malignant components are occasionally hidden within benign tissues thus complicating the diagnosis. The reasons for the variable differentiation of germ cells are still largely unknown. As transcription factors GATA-4 and GATA-6 as well as their downstream factors (e.g. HNF-4, BMP-2 and Ihh) are essential for normal yolk sac development, we studied their expression in 19 ovarian GCTs. Endodermal markers were expressed distinctively in different GCT types. The malignant endoderm in yolk sac tumors expressed all factors of endodermal development included in the study. Dysgerminomas, on the contrary, expressed only GATA-4 and, in a minority of cases, Ihh and BMP-2. The results suggest that GATA-4 and GATA-6 detected in the ovarian GCTs have retained their normal function. The fact that GATA-6 and HNF-4 are expressed exclusively in endodermal tissues indicates that these transcription factors play a role in the differentiation of germ cells towards the endodermal phenotype. Analysis of the nuclear transcription factors in tumor tissue could serve as a new informative diagnostic tool for ovarian GCTs.

Differential developmental expression of transcription factors GATA-4 and GATA-6, their cofactor FOG-2 and downstream target genes in testicular carcinoma in situ and germ cell tumors

“…In line with this study, GATA-4 and GATA-6 expression has also been demonstrated in pediatric testicular as well as non-gonadal yolk sac tumors (27,28). Moreover, GATA-4 expression has been reported in adult ovarian and testicular yolk sac tumors (25,29).…”

“…In the ovary, GATA-4 is expressed in a subpopulation of dysgerminomas (75%) (25), which is a tumor with a very close gene expression profile as compared to testicular seminomas (26). Here, we find that also most of the testicular seminomas are positive for GATA-4.…”

“…Here, we find that also most of the testicular seminomas are positive for GATA-4. Similarly to dysgerminomas (25), seminomas were mostly negative for the GATA-4 cofactor FOG-2, suggesting that GATA-4 may not function properly in seminoma tissue due to a lack of the presence of this essential cofactor. Although GATA-6 has not been detected in ovarian dysgerminomas (25), we now show that most of the testicular seminomas express this transcription factor.…”

“…Similarly to dysgerminomas (25), seminomas were mostly negative for the GATA-4 cofactor FOG-2, suggesting that GATA-4 may not function properly in seminoma tissue due to a lack of the presence of this essential cofactor. Although GATA-6 has not been detected in ovarian dysgerminomas (25), we now show that most of the testicular seminomas express this transcription factor. Taken together, although certain similarities between the corresponding ovarian and testicular tumors exist, there are also clear differences in their gene expression patterns.…”

Tissue AP-2γ and Oct-3/4, and Serum CA 125 as Diagnostic and Prognostic Markers of Malignant Ovarian Germ Cell Tumors

“…Recently, the transcription factor Oct-3/4 has been shown to be specific for DGs [14] . In our previous study, DGs were found to express the transcription factor GATA-4, whereas YSTs expressed both GATA-4 and the closely related GATA-6, which are both essential for normal yolk sac development [32] .…”