gms | German Medical Science

Objective: Infratentorial ependymoma account for approximately 60 - 70% of all ependymoma. Recent studies established two main subtypes of posterior fossa ependymoma (PF). PF type A (PFA) occur in younger children, experience more often recurrence or metastasis and are associated with a poor survival. Genetically, they show a low mutation rate und only rare copy number changes. PF type B (PFB) develop in older children, carry a better prognosis and demonstrate a high rate of copy number changes. For PFA tumors a hypermethylation phenotype has been described. Ten-eleven translocation (TET) proteins catalyze the conversion of 5-methylcytosine (5mC) to 5-hydroxymethylcytosin (5-hmC) leading to DNA demethylation. Therefore, silencing of TET2 protein is supposed to lead to DNA methylation and is linked to the hypermethylation phenotype. Previously, we have shown, that a subgroup of PF ependymoma shows methylation of the TET2 promotor. As promotor methylation might cause low protein expression, we sought to investigate the protein expression level of TET2 in PF ependymoma.

Methods: We investigated the expression of TET2 protein in 17 pediatric PF ependymoma using paraffin sections. Staining was performed with rabbit polyclonal antibody for TET2 protein. Sections were analyzed for TET2 expression using two criteria: percentage of positive tumor cells and the intensity of staining. These criteria were combined in a scoring system. Low expression was defined as a score between 0 and 1, whereas a high expression was assumed for values greater than 2. Additionally, clinical data was assessed, like age, gender, days to progression, recurrence, tumor grade and localization. Fisher’s exact test and t-test were used for statistical analysis.

Results: In 7 out of 17 (41.2%) tumors a low TET2 protein expression was detected. Only one patient with low TET2 expression had a grade III tumor, whereas tumors with high TET2 expression were grade II and III tumors. Furthermore, of these 7 patients with low TET2 expression, 6 (86%) patients developed a recurrent tumor (P=0.015). This is supported by a shorter time to progression in the subgroup of patients with low TET2 expression (522 vs 646 days).

Conclusion: In this study, we detected that a subgroup of PF ependymoma shows a low expression of TET2 protein. Despite the small sample size, we observed an association between low TET2 protein expression and a higher tumor grade as well as tumor recurrence and time to progression.