The prognostic role of tissue and serum MMP-1 and TIMP-1 expression in patients with non-small cell lung cancer

Purpose: Matrix metalloproteinase (MMP) and tissue inhibitor of matrix metalloproteinase (TIMP) play an important role in tumor invasion and progression. The aim of this study was to evaluate the prognostic role of MMP-1 and TIMP-1 in non-small cell lung cancer (NSCLC). To find out a potential serum biomarker, tissue and serum levels were investigated together. Patients and methods: For 85 surgically resected NSCLC patients who had pre-operative serum samplings, MMP-1 and TIMP-1 expression were investigated using immunohistochemistry in tumor tissue and ELISA in serum. Tumor cells and surrounding stromal cells were assessed separately. Results: Higher expression of MMP-1 in tumor cells comparing to stromal cells was related to male gender (P = 0.006), ever smoker (P = 0.004), and pooly differentiated tumor (P = 0.043). For TIMP-1, adenocarcinoma showed higher tumor cell expression, while squamous cell carcinoma showed higher stromal expression (P = 0.007). Patients with high carcinoembryonic antigen (CEA) level, the presence of vascular invasion, recurrence or death showed higher serum MMP-1 level. There was no correlation between the tissue and serum levels of MMP-1 and TIMP-1. A tumor/stroma TIMP-1 intensity ratio ≥1 was strongly associated with early recurrence in multivariate analysis (hazard ratio = 280.55, 95% confidence intervals; 11.12-7080.45; P = 0.001). High serum MMP-1 (≥3,500 pg/ml) showed a trend for short overall survival (P = 0.080). When serum MMP-1 was combined with CEA level or presence of vascular invasion, its prognostic implication was statistically significant (P = 0.045 and P = 0.015, respectively). Conclusion: The tumor/stroma TIMP-1 intensity ratio in tissue is useful to predict tumor recurrence. Serum MMP-1 level showed a possibility as a prognostic biomarker.