Loss of H3K27 tri-methylation is a diagnostic marker for malignant peripheral nerve sheath tumors and an indicator for an inferior survival
| Autor: | Ghadah A. Al Sannaa, Kelia E. Torres, Matt van de Rijn, Inge H. Briaire-de Bruijn, Pancras C.W. Hogendoorn, Davis R. Ingram, Judith V.M.G. Bovée, Brian P. Rubin, Wei Lien Wang, Alexander J. Lazar, Maurits de Vries, Sjoerd G. van Duinen, Kelsey L. Watson, Arjen H.G. Cleven |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Adult Male medicine.medical_specialty Pathology Time Factors Adolescent macromolecular substances Kaplan-Meier Estimate Biology Article California Pathology and Forensic Medicine Surgical pathology Diagnosis Differential Histones 03 medical and health sciences Young Adult 0302 clinical medicine Predictive Value of Tests medicine Neurofibroma Humans Neurofibromatosis Child Fibrosarcomatous Dermatofibrosarcoma Protuberans Aged Netherlands Tissue microarray Lysine DNA Methylation Middle Aged medicine.disease Prognosis Immunohistochemistry Texas Synovial sarcoma 030104 developmental biology Tissue Array Analysis 030220 oncology & carcinogenesis Child Preschool Female Hematopathology Neurilemmoma |
| Zdroj: | Modern Pathology, 29(6), 582-590 |
| Popis: | Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive sarcomas that can show overlapping features with benign neurofibromas as well as high-grade sarcomas. Additional diagnostic markers are needed to aid in this often challenging differential diagnosis. Recently mutations in two critical components of the polycomb repressor 2 (PRC2) complex, SUZ12 and EED, were reported to occur specifically in MPNSTs while such mutations are absent in neurofibromas, both in the setting of neurofibromatosis (NF) and sporadic cases. Furthermore, both SUZ12 and EED mutations in MPNSTs were associated with loss of H3K27 tri-methylation, a downstream target of PRC2. Therefore, we tested whether H3K27me3 immunohistochemistry is useful as a diagnostic and prognostic marker for MPNSTs. We performed H3K27me3 immunohistochemistry in 162 primary MPNSTs, 97 neurofibromas and 341 other tumors using tissue microarray. We observed loss of H3K27me3 in 34% (55/162) of all MPNSTs while expression was retained in all neurofibromas including atypical (n=8) and plexiform subtypes (n=24). Within other tumors we detected loss of H3K27me3 in only 7% (24/341). Surprisingly, 60% (9/15) of synovial sarcomas and 38% (3/8) of fibrosarcomatous dermatofibrosarcoma protuberans (DFSP) showed loss of H3K27 trimethylation. Only 1 out of 44 schwannomas showed loss of H3K27me3 and all 4 perineuriomas showed intact H3K27me3. Furthermore, MPNSTs with loss of H3K27 tri-methylation showed inferior survival compared with MPNSTs with intact H3K27 tri-methylation, which was validated in two independent cohorts. Our results indicate that H3K27me3 immunohistochemistry is useful as a diagnostic marker, in which loss of H3K27me3 favors MPNST above neurofibroma. However, H3K27me3 immunohistochemistry is not suitable to distinguish MPNST from its morphological mimicker synovial sarcoma or fibrosarcomatous DFSP. Since loss of H3K27 tri-methylation was related to poorer survival in MPNST, chromatin modification mediated by this specific histone seems to orchestrate more aggressive tumour biology. |
| Databáze: | OpenAIRE |
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