exudates and Astrocytoma

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.. 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.. 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].. 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.

Topics: Adolescent; Adult; Astrocytoma; Biomarkers, Tumor; Brain Neoplasms; DNA (Cytosine-5-)-Methyltransferase 1; DNA (Cytosine-5-)-Methyltransferases; DNA Modification Methylases; DNA Repair Enzymes; Down-Regulation; Female; Humans; Immunohistochemistry; Malaysia; Male; Middle Aged; Neoplasm Grading; Registries; Risk Factors; Tumor Suppressor Proteins; Up-Regulation; Young Adult

Alteration of the tumor suppressor gene p53 is considered to be a critical step in the development of human cancer. Changes in this gene have been detected in a wide range of human tumours, including gliomas. In glioma, the presence of p53 gene alterations has been associated with worse prognosis.. Forty-seven Malaysian adult glioma patients of the Malay race were prospectively studied over a period of 3 years where the presence of p53 mutation using cold-SSCP method and their clinical and paraclinical response were correlated.. Among these glioma patients, p53 mutations were detected in 12 tumors, an incidence rate of 25.5%. Mutations were found in 2 patients of grade II, and 5 patients both in grade III and grade IV. The sequencing results revealed the presence of base-substitutions (7) (58.3%) and frameshifts mutations (5) (41.7%). Of the base-substitutions, 57.1% were transversions and 42.9% were transitions.. Our analysis shows that 3 factors were associated with p53 mutations i.e. grade, site and consistency of tumour using univariate analysis although multivariate analysis revealed no positive on predictors of mutation. In conclusion, although p53 genetic alterations are involved in glioma patients in Malaysia, it has no impact on prognosis.

Topics: Adolescent; Adult; Amino Acid Substitution; Asian People; Astrocytoma; Base Pairing; Brain Neoplasms; DNA Mutational Analysis; Exons; Female; Frameshift Mutation; Genes, Tumor Suppressor; Glioblastoma; Humans; Magnetic Resonance Imaging; Malaysia; Male; Point Mutation; Polymerase Chain Reaction; Polymorphism, Single-Stranded Conformational; Prognosis; Prospective Studies; Tomography, X-Ray Computed; Tumor Suppressor Protein p53