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Identification of p53 as a strong predictor of survival for patients with malignant peripheral nerve sheath tumors

Brekke, Helge R.; Kolberg, Matthias; Skotheim, Rolf I.; Hall, Kirsten S.; Bjerkehagen, Bodil; Risberg, Bjorn; Domanski, Henryk LU ; Mandahl, Nils LU ; Liestol, Knut and Smeland, Sigbjorn, et al. (2009) In Neuro-Oncology 11(5). p.514-528
Abstract
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... (More)
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. Neuro-Oncology 11, 514-528, 2009 (Posted to Neuro-Oncology [serial online], Doc. D08-00271, January 30, 2009.) (Less)
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Contribution to journal
publication status
published
subject
keywords
neurofibroma, cyclin D1, MPNST, NF1, p53
in
Neuro-Oncology
volume
11
issue
5
pages
514 - 528
publisher
Oxford University Press
external identifiers
  • wos:000270494800006
  • scopus:70349628640
ISSN
1523-5866
DOI
10.1215/15228517-2008-127
language
English
LU publication?
yes
id
6d4b684b-b987-4b7c-91fa-a464fc9a2bc3 (old id 1517630)
date added to LUP
2010-01-04 16:19:07
date last changed
2017-09-03 03:39:33
@article{6d4b684b-b987-4b7c-91fa-a464fc9a2bc3,
  abstract     = {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. Neuro-Oncology 11, 514-528, 2009 (Posted to Neuro-Oncology [serial online], Doc. D08-00271, January 30, 2009.)},
  author       = {Brekke, Helge R. and Kolberg, Matthias and Skotheim, Rolf I. and Hall, Kirsten S. and Bjerkehagen, Bodil and Risberg, Bjorn and Domanski, Henryk and Mandahl, Nils and Liestol, Knut and Smeland, Sigbjorn and Danielsen, Havard E. and Mertens, Fredrik and Lothe, Ragnhild A.},
  issn         = {1523-5866},
  keyword      = {neurofibroma,cyclin D1,MPNST,NF1,p53},
  language     = {eng},
  number       = {5},
  pages        = {514--528},
  publisher    = {Oxford University Press},
  series       = {Neuro-Oncology},
  title        = {Identification of p53 as a strong predictor of survival for patients with malignant peripheral nerve sheath tumors},
  url          = {http://dx.doi.org/10.1215/15228517-2008-127},
  volume       = {11},
  year         = {2009},
}