title: Immunohistochemistry for trimethylated H3K27 in the diagnosis of malignant peripheral nerve sheath tumours.
abstract: OBJECTIVE
  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 MPNSTs 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.
  
  
  RESULTS
  We performed immunostaining studies, with monoclonal (C36B11) and polyclonal antibodies in parallel. With the monoclonal antibody, 56% of 54 conventional MPNSTs showed complete loss of staining, whereas 17% showed mosaic loss and 28% showed intact staining. Three MPNSTs showed a novel geographical pattern of complete loss. All three epithelioid MPNSTs retained intact staining. Among 232 non-MPNSTs, only two (0.9%) showed complete loss of staining. Mosaic loss was observed in 38% of non-MPNSTs, whereas the remaining 61% retained intact staining. For conventional MPNSTs, 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 MPNSTs. 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.
authors: Division of Rare Cancer Research, National Cancer Centre Research Institute, Tokyo, Japan.|Department of Orthopaedic Surgery, Keio University School of Medicine, Tokyo, Japan.
authors: Naofumi
authors: N
authors: Asano
authors: Department of Pathology and Clinical Laboratories, National Cancer Centre Hospital, Tokyo, Japan.|Rare Cancer Centre, National Cancer Centre Hospital, Tokyo, Japan.
authors: Akihiko
authors: A
authors: Yoshida
authors: Department of Clinical Genomics, National Cancer Centre Research Institute, Tokyo, Japan.
authors: Hitoshi
authors: H
authors: Ichikawa
authors: Department of Pathology and Clinical Laboratories, National Cancer Centre Hospital, Tokyo, Japan.
authors: Taisuke
authors: T
authors: Mori
authors: Department of Orthopaedic Surgery, Keio University School of Medicine, Tokyo, Japan.
authors: Masaya
authors: M
authors: Nakamura
authors: Rare Cancer Centre, National Cancer Centre Hospital, Tokyo, Japan.|Department of Musculoskeletal Oncology, National Cancer Centre Hospital, Tokyo, Japan.
authors: Akira
authors: A
authors: Kawai
authors: Department of Pathology and Clinical Laboratories, National Cancer Centre Hospital, Tokyo, Japan.
authors: Nobuyoshi
authors: N
authors: Hiraoka
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis*; D019175:DNA Methylation; D006657:Histones / Q000032:analysis*; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D009442:Neurilemmoma / Q000175:diagnosis*; D012680:Sensitivity and Specificity
chemical_list: D014408:Biomarkers, Tumor; D006657:Histones
keywords: diagnosis; epigenetics; histone; immunohistochemistry; malignant peripheral nerve sheath tumour; methylation; sarcoma