Expression of matrix metalloproteinases and their inhibitors correlates with invasion and metastasis in squamous cell carcinoma of the head and neck

Background: Matrix metalloproteinases (MMPs) have been implicated in the in vasion and metastasis of head and neck squamous cell carcinoma (HNSCC). How ever, a detailed analysis of MMPs and tissue inhibitors of MMPs (TIMPs) in relation to the biological behavior of HNSCC has yet to be performed in cli nical material. Objectives: To study a comprehensive profile of MMPs and their 2 main inhib itors in HNSCC tissue samples and to correlate the patterns of expression w ith clinicopathological characteristics, invasion, and metastasis. Design: This study included 54 consecutive patients with primary HNSCC, 27 of which showed lymph node metastasis. Expression of MMP-1, MMP-2, MMP-3, M MP-7, MMP-9, MMP-10, MMP-11, MMP-13, MMP-14, TIMP-1, and TIMP-2 was simulta neously analyzed in tissue homogenates using semiquantitative reverse trans cription-polymerase chain reaction assay. Where feasible, levels of protein and enzyme activity were confirmed by Western blot, enzyme-linked immunoso rbent assay, and substrate zymography. Conventional clinicopathological fea tures, including mode of tumor invasion, were also examined. Results: Significantly higher MMP-1, MMP-2, MMP-3, MMP-7, MMP-9, MMP-10, MM P-11, MMP-13, and TIMP-1 levels were found in tumors vs specimens of matche d normal mucosa. No difference in the distribution of MMPs and TIMPs in rel ation to age, sex, tumor site, or histological grade was observed. A signif icant correlation was demonstrated between levels of MMP-1, MMP-9, and TIMP -1 and advanced T stage and between MMP-9 expression and an infiltrative pa ttern of growth. Enhanced expression of MMP-9 was strongly correlated (P < .001) and levels of MMP-2, MMP-7, and MMP-11 were weakly correlated (P=.03- .05) with lymph node involvement. Conclusions: Overexpression of multiple MMPs and TIMPs is characteristic of HNSCC, and analysis of specific MMPs, MMP-9 in particular, might be useful for evaluating the malignant potential in individual HNSCC.