ArticleNeuro-oncology advances
Ornithine decarboxylase levels in peripheral nerve sheath tumors from NF1 patients.
Article in Neuro-oncology advances. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: The study was conducted to determine the level of ornithine decarboxylase (ODC) activity in several types of peripheral nerve sheath tumors to assess ODC as a potential target for alpha-difluoromethylornithine (DFMO), an irreversible inhibitor of ODC. Methods: A formalin-fixed paraffin-embedded peripheral nerve sheath tumor tissue microarray was developed in the Department of Anatomic Pathology, MD Anderson Cancer Center. ODC levels were measured using immunofluorescence with a polyclonal antibody to ODC and Alexa-Fluor 647 goat anti-rabbit IgG using previously validated and established methodology. Results: Nuclear and cytoplasmic ODC levels were assessed to determine surrogate ODC activity based on immunofluorescence from 11 patients with a spectrum of nerve sheath tumors, including malignant peripheral nerve sheath tumors (MPNSTs), plexiform neurofibroma, WHO Grade 1 (NF), atypical neurofibroma neoplasm of uncertain biologic potential (ANNUBP), and schwannoma. ODC activity was less than 5 nmol/30 min/min/ug ODC protein in many MPNST, NF, and schwannomas, but higher than 10 nmol/min/ug protein in ANNUBP tumors and one NF tumor. Conclusion: Nuclear ODC activity varied across peripheral nerve sheath tumors, with relatively low to moderate levels observed in MPNSTs and higher levels in ANNUBP tumors within the small cohort studied. Since DFMO, an irreversible ODC inhibitor, is more effective in slow-growing grade 2 and 3 gliomas with low ODC levels than in higher malignancy grade 4 glioma with high ODC activity, it is reasonable to assume that MPNSTs and neurofibromas, WHO grade, with relatively low to moderate levels of ODC activity may be suitable candidates for DFMO therapy. However, larger studies are needed to validate ODC activity as a predictive biomarker and to determine the therapeutic efficacy of DFMO in peripheral nerve sheath tumors.
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