title: Transcription factor AP-2gamma, a novel marker of gonocytes and seminomatous germ cell tumors.
abstract: 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-2gamma is expressed in gonocytes at weeks 12-37 of gestation, indicating a role of this transcription factor in fetal germ cell development. AP-2gamma 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-2gamma from the 12th to 37th week of gestation was observed. Furthermore, AP-2gamma was expressed abundantly in 25/25 IGCNUs, 52/53 testicular seminomas, 10/10 metastatic seminomas, 9/9 extragonadal seminomas and 5/5 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-2gamma. The expression pattern of AP-2gamma, 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-2gamma immunohistochemistry to the detection of GCT, a tumor entity with a steadily growing incidence in the male population worldwide.
authors.affiliation: Institute of Pathology, University of Bonn, Bonn, Germany. katharina.pauls@ukb.uni-bonn.de <katharina.pauls@ukb.uni-bonn.de>
authors.forename: Katharina
authors.initials: K
authors.lastname: Pauls
authors.forename: Richard
authors.initials: R
authors.lastname: Jäger
authors.forename: Susanne
authors.initials: S
authors.lastname: Weber
authors.forename: Eva
authors.initials: E
authors.lastname: Wardelmann
authors.forename: Arend
authors.initials: A
authors.lastname: Koch
authors.forename: Reinhard
authors.initials: R
authors.lastname: Büttner
authors.forename: Hubert
authors.initials: H
authors.lastname: Schorle
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis*; D002454:Cell Differentiation; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005260:Female; D005333:Fetus / Q000166:cytology / Q000196:embryology / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D009373:Neoplasms, Germ Cell and Embryonal / Q000737:chemistry* / Q000378:metabolism; D011247:Pregnancy; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D013736:Testicular Neoplasms / Q000737:chemistry* / Q000378:metabolism; D013737:Testis / Q000166:cytology / Q000196:embryology* / Q000378:metabolism*; D050656:Transcription Factor AP-2; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; C493679:TFAP2C protein, human; D050656:Transcription Factor AP-2; D014157:Transcription Factors; D019009:Proto-Oncogene Proteins c-kit