Immunohistochemistry for trimethylated H3K27 in the diagnosis of malignant peripheral nerve sheath tumours

Naofumi Asano, Akihiko Yoshida, Hitoshi Ichikawa, Taisuke Mori, Masaya Nakamura, Akira Kawai, Nobuyoshi Hiraoka

Research output: Contribution to journalArticle

24 Citations (Scopus)

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 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. Methods and 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.

Original languageEnglish
Pages (from-to)385-393
Number of pages9
JournalHistopathology
Volume70
Issue number3
DOIs
Publication statusPublished - 2017 Feb 1

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Neurilemmoma
Immunohistochemistry
Staining and Labeling
Monoclonal Antibodies
Polycomb Repressive Complex 2
Antibodies
Histones
Lysine

Keywords

  • diagnosis
  • epigenetics
  • histone
  • immunohistochemistry
  • malignant peripheral nerve sheath tumour
  • methylation
  • sarcoma

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Histology

Cite this

Immunohistochemistry for trimethylated H3K27 in the diagnosis of malignant peripheral nerve sheath tumours. / Asano, Naofumi; Yoshida, Akihiko; Ichikawa, Hitoshi; Mori, Taisuke; Nakamura, Masaya; Kawai, Akira; Hiraoka, Nobuyoshi.

In: Histopathology, Vol. 70, No. 3, 01.02.2017, p. 385-393.

Research output: Contribution to journalArticle

Asano, Naofumi ; Yoshida, Akihiko ; Ichikawa, Hitoshi ; Mori, Taisuke ; Nakamura, Masaya ; Kawai, Akira ; Hiraoka, Nobuyoshi. / Immunohistochemistry for trimethylated H3K27 in the diagnosis of malignant peripheral nerve sheath tumours. In: Histopathology. 2017 ; Vol. 70, No. 3. pp. 385-393.
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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 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. Methods and 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.",
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AU - Asano, Naofumi

AU - Yoshida, Akihiko

AU - Ichikawa, Hitoshi

AU - Mori, Taisuke

AU - Nakamura, Masaya

AU - Kawai, Akira

AU - Hiraoka, Nobuyoshi

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N2 - 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 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. Methods and 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.

AB - 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 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. Methods and 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.

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KW - epigenetics

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KW - methylation

KW - sarcoma

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