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

被引：36

作者：

Brekke, Helge R. ^{[1
,5
]}

Kolberg, Matthias ^{[1
,5
]}

Skotheim, Rolf I. ^{[1
,5
]}

Hall, Kirsten S. ^{[2
]}

Bjerkehagen, Bodil ^{[3
]}

Risberg, Bjorn ^{[3
,4
]}

Domanski, Henryk A. ^{[8
]}

Mandahl, Nils ^{[9
]}

Liestol, Knut ^{[5
,6
]}

Smeland, Sigbjorn ^{[2
]}

Danielsen, Havard E. ^{[4
,5
,6
]}

Mertens, Fredrik ^{[9
]}

Lothe, Ragnhild A. ^{[1
,5
,7
]}

机构：

[1] Norwegian Radium Hosp, Rikshosp Univ Hosp, Dept Canc Prevent, Inst Canc Res, NO-0310 Oslo, Norway

[2] Norwegian Radium Hosp, Rikshosp Univ Hosp, Div Canc Med & Radiotherapy, Dept Oncol, NO-0310 Oslo, Norway

[3] Norwegian Radium Hosp, Rikshosp Univ Hosp, Div Pathol, NO-0310 Oslo, Norway

[4] Norwegian Radium Hosp, Rikshosp Univ Hosp, Inst Med Informat, NO-0310 Oslo, Norway

[5] Univ Oslo, Ctr Canc Biomed, Oslo, Norway

[6] Univ Oslo, Dept Informat, Oslo, Norway

[7] Univ Oslo, Dept Mol Biosci, Oslo, Norway

[8] Univ Lund Hosp, Dept Pathol, S-22185 Lund, Sweden

[9] Univ Lund Hosp, Dept Clin Genet, S-22185 Lund, Sweden

来源：

NEURO-ONCOLOGY | 2009年 / 11卷 / 05期

关键词：

cyclin D1; MPNST; neurofibroma; NF1; p53; COMPARATIVE GENOMIC HYBRIDIZATION; SOFT-TISSUE SARCOMAS; CELL NUCLEAR ANTIGEN; NEUROFIBROMATOSIS TYPE-1; IMMUNOHISTOCHEMICAL ANALYSIS; MOLECULAR ANALYSIS; EXPRESSION; GENE; CHROMOSOME-17; BENIGN;

D O I：

10.1215/15228517-2008-127

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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. URL http://neuro-oncology.dukejournals.org; DOI: 10.1215/15228517-2008-127)

引用

页码：514 / 528

页数：15

共 63 条

[1] Expression patterns of cell cycle components in sporadic and neurofibromatosis type 1-related malignant peripheral nerve sheath tumors [J].