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

Abstract

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 neurofibroma/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. RECK 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.