Immunohistochemical evaluation of H3K27 trimethylation in malignant peripheral nerve sheath tumors

Hiroshi Otsuka, Kenichi Kouhashi, Masato Yoshimoto, Shin Ishihara, Yu Toda, Yuichi Yamada, Hidetaka Yamamoto, Yasuharu Nakashima, Yoshinao Oda

研究成果: ジャーナルへの寄稿記事

6 引用 (Scopus)

抄録

The histological definitive diagnosis of malignant peripheral nerve sheath tumor (MPNST) is quite difficult because the morphological features are not specific and no useful immunohistochemical marker has been identified. Loss-of-function mutations in EED or SUZ12, which encode the core subunit of polycomb repressive complex 2 (PRC2), were reported in MPNSTs, and the mutations were shown to cause inactivation of PRC2, leading to loss of trimethylation of histone H3 at lysine 27 (H3K27me3). Immunohistochemistry of H3K27me3 is expected to be a specific marker for MPNSTs. We evaluated immunohistochemical expression of H3K27me3 in MPNSTs with heterologous components and metachronous cases of MPNSTs. Among 145 MPNST samples, 50 (34.5%) showed complete loss of staining, and 45 (31.0%) showed partial loss of staining. Regarding the backgrounds of MPNSTs, 43 patients of neurofibromatosis type 1 (NF-1)-associated MPNST demonstrated 19 (44.2%) complete and 12 (27.9%) partial loss of H3K27me3. Among MPNSTs with heterologous component, almost all of MPNSTs with epithelioid differentiation (8/9 samples, 88.9%) retained H3K27me3, and malignant Triton tumors without epithelioid component lacked H3K27me3 at high rate (91.7%). Five of 20 metachronous MPNST cases showed significantly reduced expression of H3K27me3 between primary and later-occurring tumors, but in some cases increased expression of H3K27me3 in the clinical course (such as complete loss to partial loss) was observed. If the tumors are recurrent or metastatic, H3K27me3 expression should be reduced or at least maintained because loss of H3K27me3 is due to genetic mutation of EED or SUZ12. MPNSTs, especially those associated with NF-1, can occur in heterochronous and multiple patterns, and the identification of increased expression of H3K27me3 during a patient's clinical course can be helpful for determining whether the tumors are heterochronous, multiple or not. As heterochronous and multiple tumors may show lower malignancy compared to recurrent or metastatic tumors, favorable prognosis may be expected when H3K27me3 expression is increased.

元の言語英語
ページ(範囲)417-425
ページ数9
ジャーナルPathology Research and Practice
214
発行部数3
DOI
出版物ステータス出版済み - 3 1 2018

Fingerprint

Neurilemmoma
Polycomb Repressive Complex 2
Neoplasms
Neurofibromatosis 1
Mutation
Staining and Labeling
Histones
Lysine
Immunohistochemistry

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine
  • Cell Biology

これを引用

Immunohistochemical evaluation of H3K27 trimethylation in malignant peripheral nerve sheath tumors. / Otsuka, Hiroshi; Kouhashi, Kenichi; Yoshimoto, Masato; Ishihara, Shin; Toda, Yu; Yamada, Yuichi; Yamamoto, Hidetaka; Nakashima, Yasuharu; Oda, Yoshinao.

:: Pathology Research and Practice, 巻 214, 番号 3, 01.03.2018, p. 417-425.

研究成果: ジャーナルへの寄稿記事

@article{bdb59445a6ad4d2d80f97b15b7dc0d23,
title = "Immunohistochemical evaluation of H3K27 trimethylation in malignant peripheral nerve sheath tumors",
abstract = "The histological definitive diagnosis of malignant peripheral nerve sheath tumor (MPNST) is quite difficult because the morphological features are not specific and no useful immunohistochemical marker has been identified. Loss-of-function mutations in EED or SUZ12, which encode the core subunit of polycomb repressive complex 2 (PRC2), were reported in MPNSTs, and the mutations were shown to cause inactivation of PRC2, leading to loss of trimethylation of histone H3 at lysine 27 (H3K27me3). Immunohistochemistry of H3K27me3 is expected to be a specific marker for MPNSTs. We evaluated immunohistochemical expression of H3K27me3 in MPNSTs with heterologous components and metachronous cases of MPNSTs. Among 145 MPNST samples, 50 (34.5{\%}) showed complete loss of staining, and 45 (31.0{\%}) showed partial loss of staining. Regarding the backgrounds of MPNSTs, 43 patients of neurofibromatosis type 1 (NF-1)-associated MPNST demonstrated 19 (44.2{\%}) complete and 12 (27.9{\%}) partial loss of H3K27me3. Among MPNSTs with heterologous component, almost all of MPNSTs with epithelioid differentiation (8/9 samples, 88.9{\%}) retained H3K27me3, and malignant Triton tumors without epithelioid component lacked H3K27me3 at high rate (91.7{\%}). Five of 20 metachronous MPNST cases showed significantly reduced expression of H3K27me3 between primary and later-occurring tumors, but in some cases increased expression of H3K27me3 in the clinical course (such as complete loss to partial loss) was observed. If the tumors are recurrent or metastatic, H3K27me3 expression should be reduced or at least maintained because loss of H3K27me3 is due to genetic mutation of EED or SUZ12. MPNSTs, especially those associated with NF-1, can occur in heterochronous and multiple patterns, and the identification of increased expression of H3K27me3 during a patient's clinical course can be helpful for determining whether the tumors are heterochronous, multiple or not. As heterochronous and multiple tumors may show lower malignancy compared to recurrent or metastatic tumors, favorable prognosis may be expected when H3K27me3 expression is increased.",
author = "Hiroshi Otsuka and Kenichi Kouhashi and Masato Yoshimoto and Shin Ishihara and Yu Toda and Yuichi Yamada and Hidetaka Yamamoto and Yasuharu Nakashima and Yoshinao Oda",
year = "2018",
month = "3",
day = "1",
doi = "10.1016/j.prp.2017.12.015",
language = "English",
volume = "214",
pages = "417--425",
journal = "Pathology Research and Practice",
issn = "0344-0338",
publisher = "Urban und Fischer Verlag GmbH und Co. KG",
number = "3",

}

TY - JOUR

T1 - Immunohistochemical evaluation of H3K27 trimethylation in malignant peripheral nerve sheath tumors

AU - Otsuka, Hiroshi

AU - Kouhashi, Kenichi

AU - Yoshimoto, Masato

AU - Ishihara, Shin

AU - Toda, Yu

AU - Yamada, Yuichi

AU - Yamamoto, Hidetaka

AU - Nakashima, Yasuharu

AU - Oda, Yoshinao

PY - 2018/3/1

Y1 - 2018/3/1

N2 - The histological definitive diagnosis of malignant peripheral nerve sheath tumor (MPNST) is quite difficult because the morphological features are not specific and no useful immunohistochemical marker has been identified. Loss-of-function mutations in EED or SUZ12, which encode the core subunit of polycomb repressive complex 2 (PRC2), were reported in MPNSTs, and the mutations were shown to cause inactivation of PRC2, leading to loss of trimethylation of histone H3 at lysine 27 (H3K27me3). Immunohistochemistry of H3K27me3 is expected to be a specific marker for MPNSTs. We evaluated immunohistochemical expression of H3K27me3 in MPNSTs with heterologous components and metachronous cases of MPNSTs. Among 145 MPNST samples, 50 (34.5%) showed complete loss of staining, and 45 (31.0%) showed partial loss of staining. Regarding the backgrounds of MPNSTs, 43 patients of neurofibromatosis type 1 (NF-1)-associated MPNST demonstrated 19 (44.2%) complete and 12 (27.9%) partial loss of H3K27me3. Among MPNSTs with heterologous component, almost all of MPNSTs with epithelioid differentiation (8/9 samples, 88.9%) retained H3K27me3, and malignant Triton tumors without epithelioid component lacked H3K27me3 at high rate (91.7%). Five of 20 metachronous MPNST cases showed significantly reduced expression of H3K27me3 between primary and later-occurring tumors, but in some cases increased expression of H3K27me3 in the clinical course (such as complete loss to partial loss) was observed. If the tumors are recurrent or metastatic, H3K27me3 expression should be reduced or at least maintained because loss of H3K27me3 is due to genetic mutation of EED or SUZ12. MPNSTs, especially those associated with NF-1, can occur in heterochronous and multiple patterns, and the identification of increased expression of H3K27me3 during a patient's clinical course can be helpful for determining whether the tumors are heterochronous, multiple or not. As heterochronous and multiple tumors may show lower malignancy compared to recurrent or metastatic tumors, favorable prognosis may be expected when H3K27me3 expression is increased.

AB - The histological definitive diagnosis of malignant peripheral nerve sheath tumor (MPNST) is quite difficult because the morphological features are not specific and no useful immunohistochemical marker has been identified. Loss-of-function mutations in EED or SUZ12, which encode the core subunit of polycomb repressive complex 2 (PRC2), were reported in MPNSTs, and the mutations were shown to cause inactivation of PRC2, leading to loss of trimethylation of histone H3 at lysine 27 (H3K27me3). Immunohistochemistry of H3K27me3 is expected to be a specific marker for MPNSTs. We evaluated immunohistochemical expression of H3K27me3 in MPNSTs with heterologous components and metachronous cases of MPNSTs. Among 145 MPNST samples, 50 (34.5%) showed complete loss of staining, and 45 (31.0%) showed partial loss of staining. Regarding the backgrounds of MPNSTs, 43 patients of neurofibromatosis type 1 (NF-1)-associated MPNST demonstrated 19 (44.2%) complete and 12 (27.9%) partial loss of H3K27me3. Among MPNSTs with heterologous component, almost all of MPNSTs with epithelioid differentiation (8/9 samples, 88.9%) retained H3K27me3, and malignant Triton tumors without epithelioid component lacked H3K27me3 at high rate (91.7%). Five of 20 metachronous MPNST cases showed significantly reduced expression of H3K27me3 between primary and later-occurring tumors, but in some cases increased expression of H3K27me3 in the clinical course (such as complete loss to partial loss) was observed. If the tumors are recurrent or metastatic, H3K27me3 expression should be reduced or at least maintained because loss of H3K27me3 is due to genetic mutation of EED or SUZ12. MPNSTs, especially those associated with NF-1, can occur in heterochronous and multiple patterns, and the identification of increased expression of H3K27me3 during a patient's clinical course can be helpful for determining whether the tumors are heterochronous, multiple or not. As heterochronous and multiple tumors may show lower malignancy compared to recurrent or metastatic tumors, favorable prognosis may be expected when H3K27me3 expression is increased.

UR - http://www.scopus.com/inward/record.url?scp=85042383817&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85042383817&partnerID=8YFLogxK

U2 - 10.1016/j.prp.2017.12.015

DO - 10.1016/j.prp.2017.12.015

M3 - Article

C2 - 29482987

AN - SCOPUS:85042383817

VL - 214

SP - 417

EP - 425

JO - Pathology Research and Practice

JF - Pathology Research and Practice

SN - 0344-0338

IS - 3

ER -