Immunohistochemical expression of 5-Hydroxymethylcytosine (5hmC) and mutational analysis of IDH1 gene in patients with diffuse astrocytoma WHO grade II: clinical value and impact on survival

摘要

Background: Diffuse astrocytoma (WHO grade II) is a primary low-grade brain tumor of astrocytes. Although grade II astrocytoma is a relatively slow growing tumor, they have a high recurrence rate. In the 2016 edition of the WHO classification, gliomas are classified based not only on histopathologic appearance but also on molecular parameters. 5-Methylcytosine (5mC) in genomic DNA has important epigenetic functions in tumor biology. 5-Hydroxymethylcytosine (5hmC) is generated from 5mC by the action of the TET (Ten ‐ Eleven ‐ Translocation) enzymes. The highest levels of 5hmC were observed in terminally differentiated cells, while less differentiated tissue had very low 5hmC levels. Therefore, 5hmC levels were profoundly reduced in carcinoma. 5hmC regulation in malignant glioma may represent an important determinant of tumor differentiation and aggressive behavior. Aim: In the current study, we measured the level of 5hmC in diffuse astrocytoma WHO grade II and analyze its relationship with other molecular markers to investigate their potential roles as a prognostic indicator for astrocytoma patients. Patients & Methods: This prospective study included 55 adult patients with histologically confirmed grade II astrocytoma on the basis of WHO grading system. Those patients treated at Tanta University Hospitals through the period from January 2015 to June 2018. Results: In our study, low level of 5hmC was significantly associated with tumor size ≥5cm (P 0.001), but there was nonsignificant correlation between 5hmc level and age, gender, location and extent of resection. Meanwhile, there is significant correlation between high level of 5hmC and presence of isocitrate dehydrogenase1(IDH1) mutation, low level KI67 and low level of P53 (P 0.001, P=0.007 and P=0.001 respectively). Kaplan-Meier analysis was used for Correlation between overall survival and 5hmC and revealed significant correlation between overall survival and 5hmC. The 3-year overall survival for patients with high 5hmC level was 88.7% compared to 31.7% for patients with low 5hmC level (P 0.001, 95%CI=4.8-448). Conclusion: Molecular classification of grade II astrocytoma may be used to delineate it.