Expression of metastasis-associated molecules in non-small cell lung cancer and their prognostic significance.

Molecules associated with tumor invasion and metastasis have been actively investigated, but their prognostic significance has been variously reported by investigators. We evaluated the expression of matrix metalloproteinase (MMP)-1, MMP-2, MMP-3, MMP-9, MMP-10, tissue inhibitor of MMPs (TIMP)-1, TIMP-2, β-catenin, E-cadherin and cyclooxygenase-2 (COX-2) in 43 cases of non-small cell lung cancer (NSCLC). Immunohistochemistry of each marker was performed on tissue microarray paraffin blocks, and the results were determined by a semi-quantitative method using an intensity score (0-3) and percentage score (0-3). The expression scores of each marker were correlated with TNM stage and patient survival data. The expression of MMP-3 and COX-2 was significantly increased in higher stage tumors (P<0.001 and P=0.046, respectively), while a correlation with patient survival length was observed for MMP-1 and COX-2 (P=0.034 and 0.019, respectively). All stage I or II cases with increased MMP-1 expression succumbed to NSCLC within 34.1 months. Cases with low expression of both MMP-1 and COX-2 had a significantly longer survival time than cases with high expression of either of the two markers (P=0.002). These results suggest that MMP-1 and COX-2 are plausible candidate survival markers for NSCLC.