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

• Published in: Neoplasia (New York, N.Y.) N.Y.), 2007-08, Vol.9 (8), p.671-677
• Main Authors: Holtkamp, Nikola, Atallah, Isis, Okuducu, Ali-Fuat, Mucha, Jana, Hartmann, Christian, Mautner, Victor-F, Friedrich, Reinhard E., Mawrin, Christian, von Deimling, Andreas
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; Biomarkers, Tumor - biosynthesis; Biomarkers, Tumor - genetics; Biomarkers, Tumor - physiology; Disease Progression; Female; Follow-Up Studies; Gene Expression Regulation, Neoplastic - physiology; Genes, p53 - genetics; Genes, p53 - physiology; Humans; Male; Malignant peripheral nerve sheath tumor; malignant progression; matrix metalloproteinase 13; Matrix Metalloproteinase 13 - biosynthesis; Matrix Metalloproteinase 13 - genetics; Matrix Metalloproteinase 13 - physiology; Middle Aged; Mutation; Nerve Sheath Neoplasms - genetics; Nerve Sheath Neoplasms - metabolism; Nerve Sheath Neoplasms - pathology; Neurofibroma - genetics; Neurofibroma - metabolism; Neurofibroma - pathology; neurofibromatosis type 1; TP53
• ISSN: 1476-5586; 1522-8002; 1476-5586; 1522-8002
• DOI: 10.1593/neo.07304

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.