Transcription factor AP-2gamma, 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-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.

Pauls K ，Jäger R ，Weber S ，Wardelmann E ，Koch A ，Büttner R ，Schorle H ... -  《INTERNATIONAL JOURNAL OF CANCER》

Transcription factor AP-2gamma is a developmentally regulated marker of testicular carcinoma in situ and germ cell tumors.

Hoei-Hansen CE ，Nielsen JE ，Almstrup K ，Sonne SB ，Graem N ，Skakkebaek NE ，Leffers H ，Rajpert-De Meyts E ... -  《CLINICAL CANCER RESEARCH》

AP-2gamma protein expression in intratubular germ cell neoplasia of testis.

Hong SM ，Frierson HF Jr ，Moskaluk CA 《AMERICAN JOURNAL OF CLINICAL PATHOLOGY》

Spatial expression of germ cell markers during maturation of human fetal male gonads: an immunohistochemical study.

Pauls K ，Schorle H ，Jeske W ，Brehm R ，Steger K ，Wernert N ，Büttner R ，Zhou H ... -  《HUMAN REPRODUCTION》

Germ cell tumors of the gonads: a selective review emphasizing problems in differential diagnosis, newly appreciated, and controversial issues.

Ulbright TM 《MODERN PATHOLOGY》