Transcription factor GATA-4 is expressed in pediatric yolk sac tumors

Yolk sac tumors (YSTs) are malignant tumors that occur in the gonads of chi ldren and young adults, and at extragonadal sites in young children. The hi stological features of YSTs are variable and can be superimposed on other g erm cell tumor histologies. Malignant endodermal cells within YSTs express a-fetoprotein, which can be detected in tumor tissue or serum. However, add itional markers of endoderm differentiation would be beneficial for the cla ssification of these tumors. Transcription factor GATA-4 regulates the diff erentiation and. function of murine yolk sac endoderm, and its expression c orrelates with proliferation and cell survival in certain tissues. To see w hether GATA-4 plays a role in human YSTs, we surveyed its expression in hum an germ cell tumors and cell lines. Northern analysis demonstrated expressi on of GATA-4 mRNA in four human germ cell tumor lines exhibiting yolk sac e ndoderm differentiation. GATA-4 protein was detected in eight of nine pedia tric YSTs by immunohistochemistry. Three of five immature teratomas exhibit ed GATA-4 in neural blastematous cells and in cylindrical epithelium, where as all 16 mature teratomas were devoid of GATA-4. We conclude that GATA-4 i s a clinically useful marker of human YSTs and speculate that it may play a role in the maintenance of the malignant phenotype.