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.