In
head and neck cancer as well as in other
carcinomas,
tumor expansion and spread to distant sites require the secretion of destructive
enzymes that degrade the extracellular matrix. A variety of
proteases contribute to matrix destruction. Characteristics of the invasive
tumor front may reflect
tumor prognosis better than do other parts of the
tumor. Therefore, it was the aim of the present study to (i) compare central and peripheral
tumor zones for differences in the expression of
matrix-metalloproteinases (
MMP) -2 and -9 and their naturally occurring inhibitors (tissue inhibitor of
matrix-metalloproteinases (TIMP) -1 and -2), (ii) examine the morphological potential of
malignancy, and (iii) correlate these findings with clinicopathological parameters. The study population consisted of 106 surgical specimens of advanced
head and neck squamous cell carcinomas. The invasive front was graded for
malignancy, and immunohistochemical staining with MMP-2, MMP-9,
TIMP-1 and
TIMP-2 antibodies was performed. Both MMP-2 and MMP-9 were found to be significantly overexpressed at the
tumor front. The MMP-2-positive invasive front exhibited diminished overall survival times. In multivariate analysis, MMP-2 expression retained its correlation with overall survival in addition to nodal status and total
malignancy score. Expression of
TIMP-2 correlated with local
tumor invasion. We conclude that the expression of MMP-2 at the invasive front is a marker of poor survival and appears to be associated with early recurrence in initially lymph node-negative patients.