Overexpression of DNA methyltransferase 1 (DNMT1) protein in astrocytic tumour and its correlation with O6-methylguanine-DNA methyltransferase (MGMT) expression

摘要

Background: The relationship between DNA methyltransferase (DNMT) and O6-methylguanine-DNA methyltransferase (MGMT) in mediating tumorigenesis is still poorly understood. This study was carried out to investigate a correlation between DNMT1 and MGMT immunoexpression in astrocytic tumour samples. Methods: Formalin-fixed paraffin embedded tissues of astrocytic tumour patients was obtained from an observational study conducted in Hospital Universiti Sains Malaysia (USM), which was performed from January 1997 until May 2012. Patient’s histological information was retrieved from the accessible Pathology Registry. Immunohistochemistry (IHC) staining was performed to assess DNMT1 and MGMT expressions in patients’ tumours. Results: Our data showed that DNMT1 was highly expressed in high grade astrocytic tumours. A multiple regression analysis demonstrated a significant association of DNMT1 overexpression with tumour grade III and IV (GIII: OR=5.802; 95% CI: 1.059, 31.785; p value=0.043; GIV: OR=40.663; 95% CI=4.069, 406.347; p value=0.002). The MGMT protein was downregulated in tumours with higher grade as evident by a reduction mean H-score for MGMT expression from GI to GIV [28.36 ± 43.88, 28.08 ± 33.67, 26.00 ± 48.70 and 16.20 ± 35.61]. However, a good negative correlation was observed between DNMT1 and MGMT in high grade tumour [Spearman correlation test: r=-0.561, p value≤0.001 in percentage expression and r=-0.576, p value≤0.001 in H score]. Conclusion: DNMT1 overexpression was seen correlated with a reduction of MGMT protein expression in high grade astrocytic tumour. Understanding the role of these markers could be important to overcome astrocytic tumour aggresiveness.