Caspase activity is downregulated in choriocarcinoma: a cDNA array differential expression study

Background: Placental trophoblast can be considered to be pseudomalignant tissue and the pathogenesis of gestational trophoblastic diseases remains to be clarified. Aims: To examine the role of caspases 8 and 10, identified by differential expression, on trophoblast tumorigenesis. Methods: cDNA array hybridisation was used to compare gene expression profiles in choriocarcinoma cell lines (JAR, JEG, and BeWo) and normal first trimester human placentas, followed by confirmation with quantitative real time polymerase chain reaction and immunohistochemistry. Caspase 10 and its closely related family member caspase 8 were analysed. Results: Downregulation of caspase 10 in choriocarcinoma was detected by both Atlas (TM) human cDNA expression array and Atlas (TM) human 1.2 array. Caspase 10 mRNA expression was significantly lower in hydatidiform mole (p = 0.035) and chorioarcinoma (p = 0.002) compared with normal placenta. The caspase 8 and 10 proteins were expressed predominantly in the cytotrophoblast and syncytiotrophoblast, respectively, with significantly lower expression in choriocarcinomas than other trophoblastic tissues (p < 0.05). Immunoreactivity for both caspase 8 and 10 correlated with the apoptotic index previously assessed by terminal deoxynucleotidyl transferase mediated dUTP nick end labelling (p = 0.02 and p = 0.04, respectively) and M30 (p < 0.001 and p = 0.003, respectively) approaches. Conclusions: These results suggest that the downregulation of capases 8 and 10 might contribute to the pathogenesis of choriocarcinoma.