EXPRESSION OF MATRIX METALLOPROTEINASES (MMP-1 AND MMP-2) AND THEIR INHIBITORS (TIMP-1, TIMP-2 AND TIMP-3) IN ORAL LICHEN-PLANUS, DYSPLASIA, SQUAMOUS-CELL CARCINOMA AND LYMPH-NODE METASTASIS

Although matrix metalloproteinases (MMPs) are among the potential key mediators of cancer invasion, their involvement in premalignant lesion s and conditions is not clarified. Therefore, we studied, using in sit u hybridization, immunohistochemistry and zymography the expression an d distribution of MMP-1 and -2, and their tissue inhibitors (TIMPs -1, -2 and -3) in oral squamous cell carcinomas (SCC) and lymph node meta stases as well as in oral lichen planus, epithelial dysplasias and nor mal buccal mucosa. In oral SCC and lymph node metastasis, MMP-1 mRNA w as detected in fibroblastic cells of tumoral stroma. In two out of ten carcinomas studied, the peripheral cells of neoplastic islands were a lso positive. MMP-2 mRNA expression was noted in fibroblasts surroundi ng the carcinoma cells, and no signal in carcinoma cells was detected. A clear TIMP-3 mRNA expression was seen in stromal cells surrounding the neoplastic islands in all SCCs and lymph node metastases studied. TIMP-1 mRNA was detected in some stromal cells surrounding the neoplas tic islands, whereas the mRNA expression for TIMP-2 was negligible. On the other hand, expression of MMPs and TIMPs was consistently low in oral epithelial dysplasias, lichen planus and normal mucosa. In certai n epithelial dysplasias and lichen planus, MMP-1 and -2 mRNA expressio ns were detected in few fibroblasts under the basement membrane zone, but normal mucosa was completely negative. In SCC and lymph node metas tasis, a detectable immunostaining for MMP-1 in stromal cells and in s ome carcinoma cells was observed. MMP-2 immunoreactivity was detected in the peripheral cell layer in neoplastic islands and in some fibrobl ast-like cells of tumoral stroma. Immunostaining for TIMP-3 was detect ed in stromal cells surrounding the neoplastic islands. A weak positiv e staining for TIMP-1 was located in tumoral stroma, whereas the immun ostaining for TIMP-2 was negative. Using zymography, elevated levels o f MMP-2 and MMP-9 were observed in carcinoma samples in comparison wit h lichen planus or normal oral mucosa, Our results indicate that the s tudied MMPs and TIMPs are clearly up-regulated during invasion in oral SCC. However, there was also a clear, although weak, up-regulation of the expression of the MMPs but not TIMPs in some of the lichen planus and dysplastic lesions.