Different behaviour of DVL 1, DVL 2, DVL 3 in astrocytoma malignancy grades and their association to TCF 1 and LEF 1 upregulation

Key regulators of the Wnt signalling, DVL 1, DVL 2 and DVL 3, in astrocytomas of different malignancy grades were investigated. Markers for DVL 1 , DVL 2 and DVL 3 were used to detect microsatellite instability ( MSI ) and gross deletions ( LOH ), while immunohistochemistry and immunoreactivity score were used to determine the signal strengths of the three DVL proteins and transcription factors of the pathway, TCF 1 and LEF 1. Our findings demonstrated that MSI at all three DVL loci was constantly found across tumour grades with the highest number in grade II ( P  = 0.008). Collectively, LOH s were more frequent in high‐grade tumours than in low grade ones. LOH s of DVL 3 gene were significantly associated with grade IV tumours ( P  = 0.007). The results on protein expressions indicated that high‐grade tumours expressed less DVL 1 protein as compared with low grade ones. A significant negative correlation was established between DVL 1 expression and malignancy grades ( P  < 0.001). The expression of DVL 2 protein was found similar across grades, while DVL 3 expression significantly increased with malignancy grades ( P  < 0.001). The signal strengths of expressed DVL 1 and DVL 3 were negatively correlated ( P  = 0.002). However, TCF 1 and LEF 1 were both significantly upregulated and increasing with astrocytoma grades ( P  = 0.001). A positive correlation was established between DVL 3 and both TCF 1 ( P  = 0.020) and LEF 1 ( P  = 0.006) suggesting their joint involvement in malignant progression. Our findings suggest that DVL 1 and DVL 2 may be involved during early stages of the disease, while DVL 3 may have a role in later phases and together with TCF 1 and LEF 1 promotes the activation of Wnt signalling.