Expression of collagenase-1 (MMP-1), collagenase-3 (MMP-13) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) in laryngeal squamous cell carcinomas.

Abstract

Matrix metalloproteinases (MMPs) that have a proteolytic activity against the components of extracellular matrix (ECM) play an important role in the invasive and metastatic spread of tumors. The role of MMPs and tissue inhibitors of MMPs (TIMPs) in laryngeal squamous cell carcinoma (LSCC) has not been elucidated sufficiently. The aim of the present study was to evaluate the correlation between the expression of collagenase-1 (MMP-1), collagenase-3 (MMP-13) and TIMP-1, as well as the clinicopathological features of LSCCs. The expression of collagenases and TIMP-1 was examined immunohistochemically in 50 cases of surgically obtained specimens of primary LSCCs. Analyses indicated that LSCC cells as well as stromal cells expressed MMP-1, MMP-13 and TIMP-1 immunostaining. Overexpression of TIMP-1 occurred more frequently in non-metastasizing cases (P=0.009). TIMP-1 and MMP-1 staining correlated significantly with the histologic type of LSCC. The keratinizing type of carcinomas exhibited higher TIMP-1 protein expression than the nonkeratinizing variety (P=0.01). TIMP-1 staining was associated with the grade of differentiation, since it was found predominantly in well and moderately differentiated carcinomas (P=0.04). The findings confirm that expression of analyzed MMPs and TIMP-1 is characteristic of LSCC and that these enzymes contribute to the progression of tumors. TIMP-1 upregulation might exhibit lower metastatic potential in LSCCs and is linked rather with an early stage of tumor progression. It seems also that TIMP-1 expression is dependent on the grade of differentiation.