Tyrosinase immunohistochemistry can be employed for the diagnosis of atypical teratoid/rhabdoid tumours of the tyrosinase subgroup (ATRT-TYR)
Abstrakt
Atypical teratoid/rhabdoid tumour (ATRT) is a malignant brain tumour mainly occurring in young children. Mutations of chromatin remodelling complex member SMARCB1/INI1 or (rarely) SMARCA4/BRG1 are the sole recurrent genetic lesions.
On an epigenetic level, however, ATRT is a heterogeneous disease comprised of three different molecular subgroups (ATRT-TYR, ATRT-SHH and ATRT-MYC). These subgroups are characterized by distinct DNA methylome profiles, enhancer landscapes and subgroup-specific transcriptional networks.
Because molecular subgroups not only differ with regard to tumour location and age of onset, but may also show differences in overall survival, molecular subgrouping of ATRT is expected to influence clinical management. This holds especially true for the identification of ATRT-TYR, a subgroup named after the enzyme tyrosinase, which is highly expressed in this subgroup.
ATRT-TYR tumours are further characterized by overexpression of melanosomal marker genes (e.g. TYR, TYRP and MITF) and OTX2, young age of onset, infratentorial location and relatively favourable outcome.
DNA methylation profiling is a robust and reliable tool for the molecular classification of brain tumours 9 and has been successfully employed for subgrouping of ATRT. However, availability and/or legal regulations preclude first-line use of DNA methylation profiling at some institutions.
We have previously shown that tyrosinase is overexpressed at the mRNA and protein level in ATRT-TYR, but the sensitivity and specificity of tyrosinase immunohistochemistry for the diagnosis of ATRT-TYR have not yet been determined. Here, we show in a large ATRT series with known molecular subgroup status that positive tyrosinase staining is highly specific for the diagnosis of ATRT-TYR.