Malignant peripheral nerve sheath tumor: a comparison of grade, immunophenotype, and cell cycle/growth activation marker expression in sporadic and neurofibromatosis 1-related lesions

Am J Surg Pathol. 2003 Oct;27(10):1337-45. doi: 10.1097/00000478-200310000-00006.


This study investigates differences in expression of the cell cycle/growth activation markers p53, p16, and p27, and their relationship with nerve sheath cell and proliferation markers among plexiform neurofibromas (PNF), NF1-related and non-NF1 MPNSTs of different histologic grades and between benign-appearing and malignant areas in the MPNSTs associated with PNFs. Formalin-fixed, paraffin-embedded archival tissue from PNFs and MPNSTs were immunostained using the avidin-biotin-complex method with antibodies to S-100 protein (S-100), Leu7 (CD57), CD34, p16, p27, p53, Mib-1, and topoisomerase II-alpha (TopoIIalpha), with appropriate controls. All PNFs and most low-grade MPNSTs displayed diffuse or focal reactivity for S-100, Leu7, CD34, p16, and p27 and negative reactivity for p53, Mib-1, and TopoIIalpha. Most high-grade MPNSTs displayed decreased or negative reactivity to S-100, Leu7, CD34, p16, and p27 but increased reactivity to p53 (59%), Mib-1 (72%), and TopoIIalpha (72%). In addition, combined nuclear and cytoplasmic (nucleocytoplasmic) p27 staining, which was not seen in the PNF or low-grade MPNST, was observed in 33% of high-grade MPNSTs. These findings suggest that p53, p16, and p27 may be involved in tumor progression in the PNF-MPNST sequence. However, alterations in p53, p16, and p27 do not distinguish between low-grade MPNST and PNF, including PNF adjacent to high-grade MPNST. Although p53, p16, and p27 are unlikely to be reliable markers for early detection of tumor progression in MPNST, p53 reactivity was more frequent in NF1-associated high-grade MPNST and appeared to be a marker for high tumor grade. Combining immunohistochemical stains with histologic grading with careful examination of mitotic activity may provide insight into the progression of peripheral nerve sheath tumors.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Biomarkers, Tumor / analysis*
  • Cell Cycle / physiology
  • Cell Cycle Proteins / analysis
  • Cell Cycle Proteins / biosynthesis*
  • Cell Division / physiology
  • Cell Transformation, Neoplastic
  • Child
  • Female
  • Humans
  • Immunohistochemistry
  • Male
  • Nerve Sheath Neoplasms / chemistry*
  • Nerve Sheath Neoplasms / complications
  • Nerve Sheath Neoplasms / pathology*
  • Neurofibromatosis 1 / complications


  • Biomarkers, Tumor
  • Cell Cycle Proteins