Expression of melanoma cell adhesion molecule in intermediate trophoblast

Melanoma cell adhesion molecule (Mel-CAM), also known as MUC18, is a cell adhesion molecule belonging to the immunoglobulin supergene family. Because of the importance of cell adhesion molecules in trophoblastic function and development, we studied the immunohistochemical distribution of Mel-CAM in trophoblastic cells in the implantation site and the normal placenta and compared it with a variety of gestational trophoblastic lesions. Formalin-fixed paraffin-embedded tissues from 44 normal placentas, 54 implantation sites (37 normal and 17 exaggerated), 13 hydatidiform moles, 13 placental site trophoblastic tumors (PSTT), and 16 choriocarcinomas were evaluated for Mel-CAM expression in trophoblast using a Mel-CAM-specific polyclonal antibody and an immunoperoxidase method. Mel-CAM was demonstrated in intermediate trophoblastic (IT) cells in all normal placentas, implantation sites, and exaggerated placental sites. Mel-CAM staining was also found in all the multinucleated IT cells in the placental site. In contrast, Mel-CAM was not detected in either cytotrophoblast (CT) or syncytiotrophoblast (ST). Similarly, in hydatidiform moles, Mel-CAM was confined to IT. In trophoblastic neoplasms, Mel-CAM was expressed in all 13 placental site trophoblastic tumors, and in 14 of 16 (88%) choriocarcinomas. Mel-CAM staining was localized to IT in both placental site trophoblastic tumors and in choriocarcinomas. In conclusion, Mel-CAM is a specific and sensitive marker for IT differentiation in normal placentas, implantation sites, and in gestational trophoblastic lesions. The differential staining pattern of Mel-CAM provides support for a dual pathway of trophoblastic differentiation in the normal placenta and in gestational trophoblastic lesions in which CT differentiates directly into ST on the villous surface, compared with the differentiation of CT to IT and then into multinucleated IT cells in extravillous sites. In view of the difficulty in distinguishing IT from CT by conventional light microscopy, it is proposed that IT cells be defined on the basis of both their morphologic features and immunophenotype as a mononucleate trophoblastic cell that expresses Mel-CAM.