Abstract
INTRODUCTION: In the 2016 World Health Organization classification of tumors of the central nervous systems, genetic markers are included to define tumor entities in addition to histology. Especially in the lower-grade gliomas with IDH-mutant, status of chromosome 1p/19q codeletion is significant prognostic predictor, however its analysis methods such as Fluorescence in situ hybridization (FISH), comparative genomic hybridization (CGH), or Multiplex Ligation-dependent Probe Amplification (MLPA) have limitations in routine clinical practice. Since ATRX mutation and 1p/19q codeletion are mutually exclusive, ATRX immunohistochemistry (IHC) is considered to be a potential substitute for analysis of 1p/19q codeletion. Nonetheless this issue has not been verified yet. ATRX gene abnormality has various mutation patterns, and few studies have investigated whether ATRX immuno-positivity is correlated with the ATRX mutation. METHODS AND RESULTS: We performed ATRX-IHC by using two antibodies in 78 grades II and III gliomas whose whole exome sequencing was performed including ATRX, IDH and 1p/19q statuses. Among 60 IHC positive cases, 8 (13.3%) were ATRX mutant, all of which have no characteristic mutational pattern. Four (22.2%) were ATRX wildtype in 18 IHC negative cases. Some ATRX wildtype but IHC negative cases received preoperative radiochemotherapy, but it does not affect the results. CONCLUSIONS: Describing the complex IHC expression of ATRX somatic mutations, our results reveal some caveats for the diagnostic practice.