Expression of emmprin and matrix metalloproteinases (MMPs) in peripheral nerve sheath tumors: emmprin and membrane-type (MT) 1-MMP expressions are associated with malignant potential
Nabeshima, K.; Iwasaki, H.; Nishio, J.; Koga, K.; Shishime, M.; Kikuchi, M.
Anticancer Research 26(2b): 1359-1367
2006
ISSN/ISBN: 0250-7005 PMID: 16619545 Document Number: 604865
Background: Matrix metalloproteinases (MMPs), including membrane-type (MT)-MMPs, correlate with biological aggressiveness in many carcinomas. However, their roles in peripheral nerve sheath tumors (PNSTs) have rarely been investigated. Materials and Methods: In this study, the immunohistochemical expression of 6 MMPs, their 3 inhibitors and emmprin, an MMP inducer, was examined in 14 schwannomas, 14 neurofibromas and 12 malignant peripheral nerve sheath tumors (MPNSTs) in relation to malignant potentials. Results: Higher expression levels (> 3 +) of emmprin and MT1-MMP were noted in 83.3% and 16.7% of MPNSTs, respectively, versus none in schwannomas and neurofibromas (p < 0.0001). The overall expression rate (1-4 +) of MT1-MMP was 58.3% in MPNSTs versus 7.1% in both schwannomas and neurofibromas (p = 0.0093). Gelatinase A (MMP-2) showed higher expression levels (> 3 +) in all the tumors without significant differencies. Moreover, the expression patterns of MMP-1 and gelatinase B (MMP-9) could divide PNSTs into two groups: schwannoma versus neuroflibroma/MPNST Higher expression levels (> 3 +) of MMP-9 were observed in 50% of schwannomas versus none in neurofibromas and MPNSTs, while those of MMP-1 were found in 35.7% of neurofibromas and 66.7% of MPNSTs versus none in schwannomas. PECK was the main inhibitor expressed in these 3 tumors, with no significant differences. Conclusion: These results suggest that emmprin and MT1-MMP may be malignant potential-related proteins in PNSTs, and that MMP-1 and 9 may help differentiation between schwannoma and neurofibroma, especially in their plexiform types.