Objective: Improved staging systems for malignant peripheral nerve sheath tumor (MPNST) prognostication and management are needed. Consequently, we sought to identify clinical, pathologic, and molecular predictors of outcome in patients with/without neurofibromatosis type 1 (NF-1) associated MPNST.
Methods: MPNST patients treated from 1986 to 2006 (n = 140) were identified; 72 had NF-1 syndrome and 68 did not. A comprehensive database was constructed. Paraffin-embedded neurofibroma or MPNST blocks were assembled in a tissue microarray; marker expression was evaluated immunohistochemically. Univariable and multivariable analyses identified independent factors prognostic of local recurrence, distant metastasis, and disease-specific survival (DSS).
Results: DSS at 10 years was 31.6% for 87 primary disease patients, 25.9% for 26 recurrent patients, and 7.5% for 27 metastatic patients after median follow up of 91 months. The 5 years DSS for localized tumor patients was 35% for NF-1 patients and 50% for sporadic patients. MPNST >or=10 cm at diagnosis, partial resection, and metastasis development were significant negative predictors of DSS; completely resected tumors that lacked S-100 immunoreactivity had a nearly 5-fold increased risk of developing distant metastasis. Ki67, vascular endothelial growth factor, p53, and pMEK were over-expressed in MPNST compared with benign neurofibromas. Only tumor size and nuclear p53 expression were found to be independent prognosticators for MPNST DSS in a multivariable analysis.
Conclusions: MPSNT is a markedly metastatic and aggressive poor prognosis tumor. Multiple clinical, pathologic, and molecular markers identified in this study, coupled with findings from previous series, should be considered for an improved MPNST staging system useful for prognostic assessment and management decisions.