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MMP-13 and p53 in the progression of malignant peripheral nerve sheath tumors
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DOI：10.1593/neo.07304.png)
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Abstract
En 中文
Malignant peripheral nerve sheath tumors ( MPNST) are sarcomas with poor prognosis and limited treatment options. Factors contributing to tumor progression are largely unknown. We therefore examined MPNST from 22 neurofibromatosis type 1 (NF1) patients, 14 non-NF1 patients, and 14 neurofibroma patients for matrix metalloproteinase 13 (MMP-13) expression. Because wild-type and mutant p53 were shown to differentially regulate MMP-13 expression, TP53 status and protein levels were also determined. MMP-13 expression was detected in 58% of MPNST and was significantly associated with recurrent MPNST (P =.019). p53 was observed in 78% of MPNST and was found to be strongly associated with MMP- 13 expression ( P =.005). In contrast, 14 neurofibromas lacked MMP- 13 and p53 expressions. TP53 mutations were found in only 11% of MPNST and were associated with high tumor grades (P=.029). No significant association between mutant TP53 and MMP- 13 was observed, indicating that other factors drive MMP- 13 expression in MPNST. The presence of metastasis was linked to p53Pro(72) polymorphism (P=.041) and 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 and as a therapeutic target.
Keywords:
malignant peripheral nerve sheath tumor
matrix metalloproteinase 13
neurofibromatosis type 1
TP53
malignant progression
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