MMP-13, p53 in the Progression of Malignant Peripheral Nerve Sheath Tumors 1

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.