Immunohistochemical localization of epidermal growth factor receptor and myc oncogene product in human placenta: implication for trophoblast proliferation and differentiation.

Cytologic localization of epidermal growth factor receptor and myc oncogene protein product in developing human placenta was analyzed by avidin/biotin immunoperoxidase techniques with a monoclonal antibody to epidermal growth factor receptor and an affinity purified polyclonal antibody to myc protein product. Epidermal growth factor receptor was found to be almost exclusively localized to syncytiotrophoblast, paralleling the immunohistochemical localization of human chorionic gonadotropin. Since epidermal growth factor has been shown to stimulate human chorionic gonadotropin and human placental lactogen production by cultured early placental tissue, the present finding that epidermal growth factor receptor was localized to mitotically inactive syncytiotrophoblast suggests a role for epidermal growth factor receptor in the induction of differentiated function of trophoblast rather than trophoblast proliferation. By contrast, myc protein product was found to be predominantly localized to cytotrophoblastic cells, paralleling the autoradiographic distribution of replicating cytotrophoblast identified by tritiated thymidine labeling of placental explant. A close similarity between the cytologic localization of myc protein product and tritiated thymidine labeling of placental explant suggests that myc protein expression is linked to trophoblast proliferation. Furthermore, immunohistochemical cellular levels of both epidermal growth factor receptor and myc protein product were most pronounced in early placenta and declined in term placenta. Thus myc protein product and epidermal growth factor receptor seem to play a crucial role in the induction of trophoblast proliferation and differentiation, respectively, during the development of human placenta.