Transcription factor AP-2γ, a novel marker of gonocytes and seminomatous germ cell tumors

Most germ cell tumors (GCTs) arise from intratubular germ cell neoplasias (IGCNUs, also referred to as carcinoma in situ), which are thought to originate from a transformed fetal germ cell, the gonocyte. However, the nature of the molecular pathways involved in IGCNU formation remains elusive. Therefore, identification of novel oncofetal markers is an important prerequisite to further our understanding of the etiology of this tumor entity. In the present study, we show that in humans AP-2 gamma is expressed in gonocytes at weeks 12-37 of gestation, indicating a role of this transcription factor in fetal germ cell development. AP-2 gamma and c-KIT, a known target of AP-2 transcription factors, were coexpressed in gonocytes, making a direct regulation possible. With increasing differentiation of fetal testis, gradual downregulation of AP-2 gamma from the 12th to 37th week of gestation was observed. Furthermore, AP-2 gamma was expressed abundantly in 25/25 IGCNUs, 52153 testicular seminomas, 10/10 metastatic seminomas, 9/9 extragonadal seminomas and 515 dysgerminomas. In embryonal carcinomas and choriocarcinomas, focal staining only was observed. Spermatocytic seminomas, teratomas and yolk sac tumors as well as normal adult testis and various control tissues were negative for AP-2 gamma. The expression pattern of AP-2 gamma, like that of other oncofetal markers, supports the model of a gonocytal origin of IGCNUs and germ cell tumors. Finally, our results provide the basis for applying AP-2 gamma immunohistochemistry to the detection of GCT, a tumor entity with a steadily growing incidence in the male population worldwide. (c) 2005 Wiley-Liss, Inc.