Abstract American Association of Neuropathologists, Inc. Abstracts of the 88th Annual Meeting June 21–24, 2012 Chicago, IL

Background: Malignant peripheral nerve sheath tumors occurring in the setting of neurofibromatosis type 1 (NF1) are thought to be the result of malignant transformation of a preexisting (plexiform) neurofibroma. This study compared features of MPNSTs and plexiform neurofibromas in the setting of NF1 patients. Design: 12 cases of MPNSTs arising within preexisting plexiform neurofibromas were selected. For each case RNA was isolated from formalin fixed paraffin embedded (FFPE) neurofibroma and the matched MPNST. The resulting 24 samples were used to analyze the expression of 519 kinase genes using Nanostring nCounter technology. Differentially expressed kinases between neurofibromas and MPNSTs were assessed. The protein expression of some identified genes was then analyzed by immunohistochemical staining of tissue array slides. Results: Principle component analysis of kinase expression demonstrates that differential expression of kinase genes is sufficient to separate most of MPNSTs from neurofibromas. Interestingly, two of the MPNSTs clustered more closely with neurofibromas than the remaining MPNSTs. These were the only MPNSTs that were not clearly high-grade. The neurofibromas formed a tighter cluster, while MPNSTs were more heterogenous. Genes that were differentially expressed between neurofibroma and MPNST from the same individual were identified by ranking fold changes. Although there was extensive diversity in these lists, reflecting the diversity of MPNSTs, a few common genes were apparent. These included the genes of kinases important in the process of chromosome segregation. Differences in the expression of two of these latter genes were confirmed by immunohistochemical studies that showed significance differences in staining between neurofibromas and MPNSTs. Conclusion: The pattern of kinase gene expression performed on FFPE samples using this platform can separate MPNSTs and neurofibromas. Genes important for mitotic regulation may be important in the process of malignant transformation of neurofibromas.