Matrix metalloproteinase 7 and perlecan in oral epithelial dysplasia and carcinoma in situ: an aid for histopathologic recognition of their cell proliferation centers.

BACKGROUND: As one of the valuable tools for differential diagnoses of oral epithelial dysplasia, carcinoma in situ (CIS) and squamous cell carcinoma (SCC), we have proposed the immunohistochemistry for perlecan, a heparan sulfate proteoglycan (HSPG). As HSPGs have been shown to be extracellular docking molecules for matrix metalloproteinase (MMP) 7, our aim was to determine the expression mode of MMP-7 in these lesions for its possible diagnostic aid for oral borderline malignancies. METHODS: Twenty cases each of moderate dysplasia, CIS, SCC, and normal/hyperplastic/mild dysplastic epithelia of the tongue and buccal mucosa were immunohistochemically examined for MMP-1, -2 and -7 in reference to their perlecan immunolocalization. RESULTS: The expression of all three MMPs in the normal mucosal epithelium was restricted mainly to the parabasal layers. The most striking finding was strong expression of MMP-7 in epithelial dysplasia with a two-phase appearance: a clear demarcation of MMP-7-immunopositive (+) lower dysplastic/basaloid cells from non-positive upper keratinized cells. MMP-7+ cells were spread over the whole epithelial layer of CIS. In SCC, MMP-7 positivity was reduced from carcinoma cells but instead appeared in stromal cells. These expression profiles of MMP-7 resembled those of perlecan. MMP-1 and MMP-2 exhibited a similar but much weaker staining than MMP-7. CONCLUSION: These results suggest that the enhanced metabolism of perlecan associated with MMP-7 plays an important role in the cell proliferation of oral epithelia in their malignant transformation process, and that MMP-7 immunohistochemistry may be a valuable aid for identification of the cell proliferation center in oral CIS and dysplasia.