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Expression of Matrix Metalloproteinase-9 in Head and Neck Squamous Cell Carcinoma

A Potential Marker for Prognosis

Departments of ¹ Oncology and Radiotherapy and ² Pathology, Oulu University Hospital, Oulu, Finland

Purpose: Previous studies have shown that matrix metalloproteinase-9 (MMP-9) is expressed in malignant head and neck squamous cell carcinoma. The prognostic role of MMP-9 is still unclear. The aim of this study was to investigate the role of MMP-9 immunoreactive protein as a prognostic marker for survival in head and neck squamous cell carcinoma.

Experimental Design: Overexpression of the immunoreactive protein for MMP-9 was evaluated in tissue sections of 74 primary head and neck carcinomas with a monoclonal antibody using a biotin-streptavidin immunohistochemical staining method. The staining results were compared with the clinical data and to the patients’ outcome.

Results: Positive immunostaining for MMP-9 was observed in 82% of the head and neck carcinomas, 39% of the cases being extensively positive. MMP-9 protein expression was independent of the stage or the grade of the tumor. The expression of MMP-9 was prognostic for shortened survival, the 5-year cause-specific survival being 45% in MMP-9 positive cases, and 92% in cases negative for MMP-9 (P = 0.013). MMP-9 positivity also correlated to the relapse-free survival (P = 0.019). At the 5-year follow-up, the cumulative relapse-free survival rate was 79% for patients with MMP-9-negative tumor and 42% for the patients with positive immunostaining for MMP-9. High expression of MMP-9 seemed to be linked with more aggressive relapses, appearing in 33% of the cases in local relapses, in 52% of cases with lymph node relapses, and in 60% of the cases with hematogenic relapses.

Conclusions: This is the first study with a long follow-up showing that the immunoreactive protein of MMP-9 in head and neck carcinoma is associated with shortened relapse-free and cause-specific survival, suggesting that MMP-9 has a role in tumor progression of head and neck carcinomas, as well as in estimation of the prognosis of these diseases.

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