Title: Immunohistochemistry for trimethylated H3K27 in the diagnosis of malignant peripheral nerve sheath tumours
Abstract: Aims The diagnosis of a malignant peripheral nerve sheath tumour ( MPNST ) can be challenging, as the morphological criteria and existing immunohistochemical markers are not entirely specific. The recent discovery of frequent inactivation of polycomb repressive complex 2 in MPNST s suggests that immunohistochemical detection of histone 3 trimethylated on lysine 27 (H3K27me3) could be of diagnostic help. This study aimed to clarify the utility of this marker. Methods and results We performed immunostaining studies, with monoclonal (C36B11) and polyclonal antibodies in parallel. With the monoclonal antibody, 56% of 54 conventional MPNST s showed complete loss of staining, whereas 17% showed mosaic loss and 28% showed intact staining. Three MPNST s showed a novel geographical pattern of complete loss. All three epithelioid MPNST s retained intact staining. Among 232 non‐ MPNST s, only two (0.9%) showed complete loss of staining. Mosaic loss was observed in 38% of non‐ MPNST s, whereas the remaining 61% retained intact staining. For conventional MPNST s, complete loss of H3K27me3 was significantly associated with a higher TNM stage ( P = 0.013), a deeper location ( P = 0.004), and the presence of heterologous differentiation ( P = 0.003). Polyclonal antibodies did not recognize 34% of cases that showed complete loss with the use of monoclonal antibodies. Conclusions We confirmed that complete loss of H3K27me3 immunohistochemical staining is moderately sensitive and highly specific for MPNST s. In contrast to prior studies, we found that mosaic loss of H3K27me3 staining is non‐specific, and caution that such a pattern should not be considered to be diagnostic. We recommend the use of a monoclonal antibody to obtain better performance.
Publication Year: 2016
Publication Date: 2016-11-10
Language: en
Type: article
Indexed In: ['crossref', 'pubmed']
Access and Citation
Cited By Count: 53
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