Copyright 2009 by the Society for Neuro-Oncology
Identification of p53 as a strong predictor of survival for patients with malignant peripheral nerve sheath tumors
vard E. DanielsenDepartment of Cancer Prevention, Institute for Cancer Research (H.R.B., M.K., R.I.S., R.A.L.), Division of Cancer Medicine and Radiotherapy, Department of Oncology (K.S.H., S.S.), Division of Pathology (B.B., B.R.), and Institute for Medical Informatics (B.R., H.E.D.), Norwegian Radium Hospital, Rikshospitalet University Hospital, Oslo, Norway; Centre for Cancer Biomedicine (H.R.B., M.K., R.I.S., K.L., H.E.D., R.A.L.), Department of Informatics (K.L., H.E.D.), and Department of Molecular Biosciences (R.A.L.), University of Oslo, Oslo, Norway; Department of Pathology (H.A.D.) and Department of Clinical Genetics (N.M., F.M.), Lund University Hospital, Lund, Sweden
Address correspondence to Ragnhild A. Lothe, Department of Cancer Prevention, Institute for Cancer Research, Norwegian Radium Hospital, Rikshospitalet University Hospital, Montebello, NO-0310 Oslo, Norway (ragnhild.a.lothe{at}rr-research.no).
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Abstract |
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The purpose of this study was to identify new prognostic biomarkers with clinical impact in malignant peripheral nerve sheath tumor (MPNST), a highly aggressive malignancy for which no consensus therapy exists besides surgery. We have used tissue microarrays (TMAs) to assess in situ expression of 14 cell-cycle–regulating proteins in 64 well-characterized MPNST patients: 36 sporadic and 28 with neurofibromatosis type 1 (NF1). We developed a new software application for evaluation and logistics of the TMA images and performed a literature survey of cell cycle proteins in MPNST. For NF1-associated patients, there was a clear association between nuclear expression of p53 and poor survival (p = 0.004). Among the other proteins analyzed, we also found significant associations between survival and clinical variables, but none were as strong as that for p53. For the total series of MPNSTs, p53 was shown to be an independent predictor of survival, and patients without remission, with tumor size larger than 8 cm, and with positive p53 expression had a 60 times greater risk of dying within the first 5 years compared with the remaining patients (p = 0.000002). This is the most comprehensive study of in situ protein expression in MPNST so far, and expressed p53 was found to be a strong surrogate marker for outcome. Patients in complete remission with a primary p53-positive MPNST diagnosis may be considered in a high-risk subgroup and candidates for adjuvant treatment.
Keywords: cyclin D1, MPNST, neurofibroma, NF1, p53
Received October 10, 2008; Accepted January 5, 2009