Neurofibromin specific antibody differentiates malignant peripheral nerve sheath tumors (MPNST) from other spindle cell neoplasms
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- 作者：David E. Reuss (1) (2)
Antje Habel (2)
Christian Hagenlocher (1)
Jana Mucha (1)
Ulrike Ackermann (3)
Claudia Tessmer (3)
Jochen Meyer (1)
David Capper (1) (2)
Gerhard Moldenhauer (4)
Victor Mautner (5)
Pierre-Olivier Frappart (1)
Jens Schittenhelm (6)
Christian Hartmann (7)
Christian Hagel (8)
Kathrin Katenkamp (9)
Iver Petersen (9)
Gunhild Mechtersheimer (10)
Andreas von Deimling (1) (2) - 刊名：Acta Neuropathologica
- 出版年：2014
- 出版时间：April 2014
- 年：2014
- 卷：127
- 期：4
- 页码：565-572
- 全文大小：713 KB
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Antje Habel (2)
Christian Hagenlocher (1)
Jana Mucha (1)
Ulrike Ackermann (3)
Claudia Tessmer (3)
Jochen Meyer (1)
David Capper (1) (2)
Gerhard Moldenhauer (4)
Victor Mautner (5)
Pierre-Olivier Frappart (1)
Jens Schittenhelm (6)
Christian Hartmann (7)
Christian Hagel (8)
Kathrin Katenkamp (9)
Iver Petersen (9)
Gunhild Mechtersheimer (10)
Andreas von Deimling (1) (2)
1. German Cancer Consortium (DKTK), Clinical Cooperation Unit Neuropathology, German Cancer Research Center, DKFZ, Im Neuenheimer Feld 224, 69120, Heidelberg, Germany
2. Department of Neuropathology, Institute of Pathology, Ruprecht-Karls-University Heidelberg, Heidelberg, Germany
3. Monoclonal Antibody Facility, German Cancer Research Center, Heidelberg, Germany
4. Department of Translational Immunology, German Cancer Research Center, Heidelberg, Germany
5. Department of Neurology, University Hospital Hamburg-Eppendorf, Hamburg, Germany
6. Department of Neuropathology, Institute of Pathology and Neuropathology, University Tübingen, Tübingen, Germany
7. Department of Neuropathology, Institute of Pathology, Medizinische Hochschule Hannover, Hannover, Germany
8. Institute of Neuropathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
9. Institute of Pathology, University Hospital of Jena, Jena, Germany
10. Institute of Pathology, University of Heidelberg, Heidelberg, Germany - ISSN：1432-0533
文摘
Malignant peripheral nerve sheath tumors (MPNST) derive from the Schwann cell or perineurial cell lineage and occur either sporadically or in association with the tumor syndrome neurofibromatosis type 1 (NF1). MPNST often pose a diagnostic challenge due to their frequent lack of pathognomonic morphological or immunohistochemical features. Mutations in the NF1 tumor suppressor gene are found in all NF1-associated and many sporadic MPNST. The presence of NF1 mutation may have the potential to differentiate MPNST from several morphologically similar neoplasms; however, mutation detection is hampered by the size of the gene and the lack of mutational hot spots. Here we describe a newly developed monoclonal antibody binding to the C-terminus of neurofibromin (clone NFC) which was selected for optimal performance in routinely processed formalin-fixed and paraffin-embedded tissue. NFC immunohistochemistry revealed loss of neurofibromin in 22/25 (88?%) of NF1-associated and 26/61 (43?%) of sporadic MPNST. There was a strong association of neurofibromin loss with deletions affecting the NF1 gene (P?<?0.01). In a series of 256 soft tissue tumors of different histotypes NFC staining showed loss of neurofibromin in 2/8 myxofibrosarcomas, 2/12 (16?%) pleomorphic liposarcomas, 1/16 (6?%) leiomyosarcomas, and 4/28 (14?%) unclassified undifferentiated pleomorphic sarcomas. However, loss of neurofibromin was not observed in 22 synovial sarcomas, 27 schwannomas, 23 solitary fibrous tumors, 14 low-grade fibromyxoid sarcomas, 50 dedifferentiated liposarcomas, 27 myxoid liposarcomas, 13 angiosarcomas, 9 extraskeletal myxoid chondrosarcomas, and 7 epitheloid sarcomas. Immunohistochemistry using antibody NFC may substantially facilitate sarcoma research and diagnostics.