Degradation of tenascin-C and activity of matrix metalloproteinase-2 are associated with tumor recurrence in early stage non-small cell lung cancer.

Abstract

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. 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. 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). 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.