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Degradation of Tenascin-C and Activity of Matrix Metalloproteinase-2 Are Associated with Tumor Recurrence in Early Stage Non-Small Cell Lung Cancer

Departments of Thoracic and Cardiovascular Surgery [M. C., K. O., M. T., H. S., I. Y.] and Pathology [I-Y. K., T. Y.], Mie University School of Medicine, Tsu, Mie, Japan 514-8507

Purpose: To find out an effective prognostic factor for early stage non-small cell lung cancer (NSCLC), we examined the relationship of the degree of tenascin-C (TN-C) degradation in relapsed NSCLC tumors with the prognosis of the patients. The molecular mechanism of TN-C degradation was also evaluated.

Experimental Design: In 63 stage-1 NSCLC patients, TN-C protein was analyzed by Western blotting, and the activity of matrix metalloproteinase (MMP)-2 was examined by gelatin zymography in 23 stage-1 NSCLC patients.

Results: Degradation of TN-C was detected in 12 of 63 patients. TN-C degradation was detected in 9 of 17 patients (52.9%) that showed local and distant cancer recurrences. In short, in 9 of 12 patients (75%) showing TN-C degradation, lung cancer recurrence was recognized. The actual frequency of free-from-recurrence at 4 years was 28.1% in patients with tumors showing TN-C degradation, and actual frequency of free-from-recurrence at 4 years and 10 years was 82.1% and 76.6% in patients without TN-C degradation (P < 0.001). In 23 stage-1 NSCLC patients, in tumors with or without degraded TN-C, the mean ratio of tumor:normal-tissue of activated MMP-2 was 3.5 ± 0.4 or 1.54 ± 0.4, respectively. Significantly increased activity of MMP-2 was recognized in tumors showing TN-C degradation (P < 0.001).

Conclusions: These results suggest that TN-C degradation is a reliable marker for recurrence potential of stage-1 NSCLC and that MMP-2 may be a protease breaking down TN-C in lung cancer.

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