Metalloproteinases and their inhibitors in squamous cell carcinoma of the hypopharynx: indicators of individual tumor aggressiveness.

BACKGROUND

Matrix metalloproteinases (MMP) are proteolytic enzymes capable of degrading connective tissue components. MMP activity is modulated by tissue inhibitors of metalloproteinases (TIMP). Imbalanced secretion of certain MMP or disturbances in the differential control of MMP by TIMP have been implicated in the invasive potential of malignant tumors.

METHODS

Thirty-nine surgically obtained specimens of the hypopharynx were immunohistochemically stained with antibodies against MMP-1, MMP-2, MMP-3, MMP-9 and their inhibitors, TIMP-1 and TIMP-2. Thirty-one samples derived from primary tumors (PT-group) and 8 samples from recurrent tumors (RT-group).

RESULTS

In the PT-group, MMP-1 was expressed in almost all tumors. Expression of TIMP-1 was rarer than of TIMP-2. Relapse occurred in 8/31 cases expressing MMP-1 or MMP-9 (4 cases each). Staining for TIMP-1 was negative in these patients, while TIMP-2 was expressed in most cases. In the RT-group, MMP-1 and MMP-9 stained positive in an almost equal number of cases. Only TIMP-1 was not expressed in any tumor. Patients who died of tumor were uniformly negative for TIMP-1.

CONCLUSIONS

The findings suggest that the presence of MMP-9 and concomitant lack of TIMP-1 serve as prognostic indicators of tumor aggressiveness and increased risk of relapse.