Objectives: Squamous cell carcinoma of the oral cavity (SCC) is a highly invasive tumor that spreads through degradation of the basement membrane and extracellular matrix. Verrucous carcinoma of the oral cavity is a low grade variant of oral SCC. Matrix metalloproteinases (MMPs) have been implicated in cancer invasion. The aim of this study was to investigate if the pattern of MMP expression contributes to the differences in the biological behavior of oral SCC and verrucous carcinoma. Methods: Tissue sections were analyzed by specific immunohistochemical and in situ hybridization techniques. Results: The less aggressive nature of oral verrucous carcinoma may be connected to its MMP expression profile. Typically verrucous carcinoma were devoid of epithelial MMP-3, -7, -9, –12 and –13 expression compared to SCCs. MMP-19 was expressed by epithelial keratinocytes in hyperproliferative areas of verrucous hyperplasia, verrucous carcinoma and SCC, but was absent in the invasive cancer cell nests of SCC. MMP-26 was expressed by hyperproliferative keratinocytes in verrucous carcinoma as well as by invasive cancer cells in SCCs. MMP-10 was expressed widely in the epithelium of all SCC and it was concentrated at the invasive cancer front. Conclusions: Absence of MMP-7, -9, -12 and –13 from epithelial cells may serve as a good prognostic marker of non-invasive oral carcinoma. Moreover, blocking the activity of invasion-specific MMPs might offer novel therapeutic modalities at early stages of oral carcinoma.

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