Immunohistochemical investigation of topoIIβ, H3K27me3 and JMJD3 expressions in medulloblastoma

Abstract

Topoisomerase IIβ (topoIIβ) is a nuclear enzyme specifically expressed in neurons, and plays an important role in the development of the cerebellum. To date, the expression of topoIIβ protein in medulloblastoma (MB) has not been investigated. In this study, 16 MB specimens including 10 classical subtypes of MB and 6 desmoplastic subtypes of MB (DMB), along with 5 normal cerebellum samples, were obtained from clinics. With immunohistochemical staining, prominently expressed topoIIβ was seen in normal cerebellar tissues, while there was no or less pronounced staining in classical MB cells. Interestingly, on comparing topoIIβ expression in different regions of DMB samples, relatively high levels of topoIIβ were revealed within nodules composed of differentiated neurocytic cells, which are known to predict a favorable clinical outcome for MB. We also examined the expression of two epigenetic factors, H3K27me3 and JMJD3 in the different tissues. Very high levels of H3K27me3 were found in all MB samples, except the intranodules of DMB, where JMJD3 expression was more prominent. Furthermore, a negative correlation between topoIIβ and H3K27me3 in MB was revealed in this study. Thus, our data primarily indicate that topoIIβ can be used to estimate neuronal differentiation in MB, and may serve as a target for improving the survival rates for this condition. We speculate that H3K27me3 repression of topoIIβ at the transcriptional level may occur, although this needs to be verified using larger numbers of MB samples in future experiments.