The Expression of bcl-2 protein in Gestational Trophoblastic Disease and Chorionic Villi

Kim, Y T; Huh, J R; Kim, J H; Na, J H; Teon, K S; Kong, H S; Kim, Y M; Nam, C H; Mok, J E

Abstract

Bcl-2 is a proto-oncogene that inhibits apoptosis induced by hormones and cytokines and thus extends cell survival, exposing the cell to oncogenic stimuli. It is expressed in various normal tissues and neoplasia, often associated with prognostic significance. In normal placenta, only syncytiotrophoblasts have been found to express bcl-2. The role of bl-2 in gestational trophoblastic disease (GTD) is largely undetermined. In this study, the authors examined the possible role of bcl-2 in oncogenesis of GTD. Bcl-2 protein in 34 cases of GTD was examined by immunohistochemical staining on routinely processed paraffin-embedded tissues, using antihuman mouse monoclonal antibody according to standard streptavidine biotin method. Cases included 21 hydatidiform moles (H-mole), 7 invasive moles, 4 choriocarcinomas and 2 placental site trophoblastic tumors (PSTT). As controls, we included 5 first trimester pregnancy, 5 abortions and 4 normal endometrium. In normal first trimester placental tissues, distinct strong diffuse cytoplasmic staining for bcl-2 was observed only in syncytiotrophoblastic cells, but not in cytotrophoblasts or intermediate trophoblasts. The reaction was stronger than in gestational endometrial glandular cells. In H-moles, diffuse cytoplasmic staining of syncytiotrophoblasts was noted in 17 cases (81.0%). The reaction was similar to, or weaker than normal in placental tissue. In invasive moles, weak to moderate staining was noted in trophoblasts invading myometrium in 3 cases (42.9%). In choriocarcinomas, weak cytoplasmic stain was seen in syncytiotrophoblasts in 1 cases (25.0%). Two case of PSTT showed diffuse cytoplasmic staining in some syncytiotrophoblasts and intermediate trophoblasts. There is a significant inverse relationship between the expression of bcl-2 and the aggressiveness of GTD. This study shows that the exclusive localization of bcl-2 in syncytiotrophoblasts is well maintained in hydatidiform moles and invasive moles, whereas almost absent staining is seen in choriocarcinoma and PSTT. Inverse relationship between bcl-2 expression and aggressiveness of GTD suggests that other molecular events are required for tumorigenesis of GTD, by which expression of bcl-2 can be altered or bcl-2 function as a tumor suppressor gene depending on cell type.