Expression pattern of the AP-1 family of transcription factors in Gestational Trophoblastic Diseases (GTD)

Abstract

The human placenta is an endocrine tissue with a unique capacity for rapid, but tightly controlled proliferation and invasion. Gestational trophoblastic diseases (GTD) are placental pathologies with endocrine activity and partially malignant potential and include hydatidiform moles (HM), placental site nodules (PSN) and tumors such as placental site trophobastic tuor (PSTT) and choriocarcinomas (CC). The AP-1 family of transcription factors (activating protein-1) is composed of the cellular homologs of the Jun and Fos oncoproteins, immediately involved in cellular proliferation, differentiation and invasion processes as well as in the regulation of endocrine genes. We have recently described the expression pattern of the AP-1 factors in the normal human placenta. Their systematic expression in GTD has not been studied so far. For this reason in the present study we investigated the expression pattern of AP-1 family in GTD and compared it to the expression in normal placenta by using immunohistochemistry with specific polyclonal antibodies against all members of the AP-1 family (JunB, JunD, c-Jun, c-Fos, FosB, Fra1, Fra2). Immunohistochemistry was performed on nomal human placentas (positive control) and on 20 cases of GTD including four choriocarcinomas, one PSTT, one PSN and fourteen hydatidiform moles. In the normal placenta and in hydatidiform molar samples most AP-1 factors (especially c-Jun, JunD and Fra2) were expressed in the intermediate (extravillous) trophoblast. In addition, in molar lesions strong expression was found in trophoblast proliferating from the surface of villi. There was only weak expression of JunB and Fra2 in small fractions of villous cyto- and sycytiotrophoblast nuclei. In choriocarcinomas, PSN and especially in PSTT there was a strong expression for c-Jun, JunD, Fra1 and Fra2. The specific localization to extravillous trophoblast and their expression pattern in GTD indicates that the AP-1 family of transcription factors is probably implicated in regulating proliferation and invasion of trophoblast.