Introduction: The human placenta is a rapidly growing and differentiating organ. When the trophoblast escapes from normal control during pregnancy, gestational trophoblastic diseases may develop that comprises of benign hydatidiform moles, malignant moles, to choriocarcinoma. The cellular mechanisms underlying the formation of gestational choriocarcinoma remain poorly understood and recent studies have demonstrated that the β-catenin/E-cadherin complex plays a central role in the terminal differentiation of human trophoblasts. We hypothesized that β-catenin might have a role in choriocarcinoma formation and attempted to verify this hypothesis by studying β-catenin expression in choriocarcinoma and its premalignant form. Materials and Methods: We investigated the expression pattern of β-catenin in paraffin-embedded specimens consisting of 60 normal gestation products (NGP), 60 complete hydatidiform moles (CHM) and 10 choriocarcinomas using semi-quantitative immunohistochemistry presented as the immunohistochemical (IHC) score. In addition, approximately 400 cytotrophoblasts each in 40 NGP and 10 choriocarcinoma from the same batch of samples as above were microdissected for quantitative reverse transcriptase polymerase chain (Q-RT-PCR) reaction to measure β-catenin mRNA concentrations. Results: Our results showed that β-catenin was consistently expressed in the nuclei of cytotrophoblasts but not syncytiotrophoblasts in the chorionic villi in the NGP. β-catenin nuclear expression was decreased in cytotrophoblasts in CHM and it was absent in choriocarcinoma cells. The IHC scores for β-catenin nuclear expression for all specimens in each clinical stage are shown in figure 1 and the decrease was statistically significant (Kruskal-Wallis test, p<0.05). In Q-RT-PCR, β-catenin mRNA expression was positive in 25% and 30% of normal gestational products and choriocarcinoma, with median copy numbers of 43,000 and 17,300 per 400 cytotrophoblasts, respectively. Conclusions: Decreased β-catenin expression is a feature of gestational trophoblastic diseases. These findings thus suggest that β-catenin may play a role in trophoblast differentiation during normal placental development.
[Proc Amer Assoc Cancer Res, Volume 46, 2005]