MMPs are a family of zinc metalloproteases capable of degrading all components of host connective tissues. MMPs have been implicated in tumor cell detachment and migration, which are essential features of cancer invasion and metastasis. Tumor tissue is heterogenous. Transformed cells within the tissue have differing metastatic potentials and differing patterns of MMP expression. Stromal cells and inflammatory cells in the tissue also express MMPs. Objectives: Our aim was to assess the MMP distribution in tumor tissue specimens from oral carcinoma variants of differing invasive and metastatic properties and to correlate MMP expression patterns with the tumor characteristics. Methods: Immunohistochemical techniques were used to assess and compare MMP distributions in paraffin embedded specimens of oral verrucous (VC), squamous cell (SCC), and spindle cell (SpC) carcinomas. Results: The non-metastatic VC showed moderate expression of MMP-3 & -9 in both tumor and stromal cells with enhanced expression at sites of inflammatory cell accumulation, strong cytoplasmic expression of MMP-7, and no expression of MMP-2 & -14. In SCC, there was strong stromal expression of MMP-1, -13, -2, & -3 by fibroblasts at the tumor periphery and strong cytoplasmic expression of MMP-3, -7, & -9 in advancing tumor nests. The deeply invasive SpC showed enhanced stromal expression of MMP-1, -13, -2, & -3 and stronger expression of MMP-7 & -9, especially at sites of inflammation. Conclusions: Interstitial MMPs (MMP-3 & -9) may play a role in VC invasive growth, and the absence of MMP-2 expression may be related to the non-metastatic properties of VC. MMP-1, -13, -2, & -3 expression is associated with progression to higher metastatic potential. During tumor progression, the change to spindle cell morphology may be associated with a switch to the stromal MMP pattern, while maintaining strong MMP-7 & -9 expression. Supported in part by NIDCR training grant DE07258

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