MMP-13 and p53 in the progression of malignant peripheral nerve sheath tumors.
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.
Holtkamp
Nikola
N
Institute of Neuropathology, Charité-Universitätsmedizin Berlin, Berlin, Germany. nikola.holtkamp@charite.de
Atallah
Isis
I
Okuducu
Ali-Fuat
AF
Mucha
Jana
J
Hartmann
Christian
C
Mautner
Victor-F
VF
Friedrich
Reinhard E
RE
Mawrin
Christian
C
von Deimling
Andreas
A
D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D016158:Genes, p53 / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008297:Male; D053509:Matrix Metalloproteinase 13 / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D008875:Middle Aged; D009154:Mutation; D018317:Nerve Sheath Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D009455:Neurofibroma / Q000235:genetics / Q000378:metabolism / Q000473:pathology