MMP-13, p53 in the Progression of Malignant Peripheral Nerve Sheath Tumors
Malignant peripheral nerve sheath tumors (MPNST) are sarcomas with poor prognosis, limited treatment options. Factors contributing to tumor progression are largely unknown. We therefore examined MPNST from 22 neurofibromatosis type 1 (NF1) patients, 14 nonNF1 patients, 14 neurofibroma patients for m...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2007-08-01
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| Series: | Neoplasia: An International Journal for Oncology Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1476558607800741 |
| Summary: | Malignant peripheral nerve sheath tumors (MPNST) are sarcomas with poor prognosis, limited treatment options. Factors contributing to tumor progression are largely unknown. We therefore examined MPNST from 22 neurofibromatosis type 1 (NF1) patients, 14 nonNF1 patients, 14 neurofibroma patients for matrix metalloproteinase 13 (MMP-13) expression. Because wild-type, mutant p53 were shown to differentially regulate MMP-13 expression, TP53 status, protein levels were also determined. MMP-13 expression was detected in 58% of MPNST, was significantly associated with recurrent MPNST (P = .019). p53 was observed in 78% of MPNST, was found to be strongly associated with MMP-13 expression (P = .005). In contrast, 14 neurofibromas lacked MMP-13, p53 expressions. TP53 mutations were found in only 11% of MPNST, were associated with high tumor grades (P = .029). No significant association between mutant TP53, MMP-13 was observed, indicating that other factors drive MMP-13 expression in MPNST. The presence of metastasis was linked to p53Pro72 polymorphism (P= .041), shorter survival. In summary, our data suggest that MMP-13 expression in nerve sheath tumors is coupled with malignant progression. Therefore, MMP-13 may serve as a marker for progression, as a therapeutic target. |
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| ISSN: | 1476-5586 1522-8002 |