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Transcription factor AP‐2γ, a novel marker of gonocytes and seminomatous germ cell tumors
Author(s) -
Pauls Katharina,
Jäger Richard,
Weber Susanne,
Wardelmann Eva,
Koch Arend,
Büttner Reinhard,
Schorle Hubert
Publication year - 2005
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.20913
Subject(s) - gonocyte , seminoma , biology , germ cell , germ cell tumors , embryonal carcinoma , yolk sac , pathology , immunohistochemistry , cancer research , cellular differentiation , medicine , microbiology and biotechnology , immunology , embryo , genetics , gene , chemotherapy
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‐2γ is expressed in gonocytes at weeks 12–37 of gestation, indicating a role of this transcription factor in fetal germ cell development. AP‐2γ 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‐2γ from the 12th to 37th week of gestation was observed. Furthermore, AP‐2γ 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‐2γ. The expression pattern of AP‐2γ, 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‐2γ immunohistochemistry to the detection of GCT, a tumor entity with a steadily growing incidence in the male population worldwide. © 2005 Wiley‐Liss, Inc.