Expression of matrix metalloproteinases MMP-2, MMP-9 and their tissue inhibitors TIMP-1,-2, and-3 in benign and malignant tumours of the salivary gland

Aims: The balance between matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) is involved in the morphogenesis of the normal salivary gland as well as in mechanisms of tumour invasion and metastasis. Our aim was to analyse protein and mRNA expression of MMPs and TIMPs in normal salivary gland tissue and in various salivary gland neoplasms. Methods and results: Immunohistochemistry for MMP-2, MMP-9, TIMP-1, -2 and -3 was performed in 20 malignant and six benign salivary gland tumours. The immunoscores of MMP-2 were significantly higher in carcinomas compared with adenomas (P = 0.0028). The MMP/TIMP ratio was significantly higher in carcinomas than in adenomas (P = 0.0097). In mucoepidermoid carcinomas MMP-2 expression was preferentially observed in the intermediate cell type. Neoplastic acinar cells of acinic cell carcinoma demonstrated de novo expression of MMP-2, MMP-9, TIMP-1, and TIMP-2. Immunoscores of TIMP-3 were not decreased in malignant tumours compared with adenomas. In accordance with the immunostaining of MMP-2 and -9, gelatinolytic activity could be demonstrated by in-situ zymography. The mRNA expression of MMPs and TIMPs analysed by real-time reverse transcriptase-polymerase chain reaction in three malignant and two benign tumours and their corresponding normal tissue did not generally correlate with their protein expression. Conclusions: Our findings suggest a disturbed balance between MMP and TIMP in malignant salivary gland tumours. MMP-2 expression in particular seems to be related to the invasive properties and the malignant potential of these tumours.