Expression of tissue inhibitor of metalloproteinase‐3 (TIMP‐3) and its prognostic significance in resected non‐small cell lung cancer

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Abstract
Background and Objectives Tissue inhibitor of metalloproteinase‐3 (TIMP‐3) inhibits the activity of metalloproteinases that play important roles in development and progression of malignant tumors. We conducted a retrospective study of TIMP‐3 expression in resected non‐small cell lung cancer (NSCLC). Methods TIMP‐3 expression was examined immunohistochemically in primary tumor specimens from 143 patients who underwent complete resection for NSCLC. Correlations between TIMP‐3 expression grade and tumor histology, TNM classification, MMP‐2 and MMP‐9 expression grade, VEGF expression grade, intra‐tumoral microvessel density, proliferative index, apoptosis index, and prognosis were analyzed. Results TIMP‐3 expression was low in 40, moderate in 71, and high in 32 patients. Higher TIMP‐3 expression was seen in squamous cell carcinoma than in adenocarcinoma (P = 0.001), and reduced TIMP‐3 expression was significantly associated with nodal involvement (P = 0.016) and advanced pathologic stage (P = 0.036). MMP‐2 expression was reduced along with enhanced TIMP‐3 expression (P = 0.010). The 5‐year overall survival rates of low, moderate, and high TIMP‐3 patients were 53, 64, and 84%, respectively (P = 0.037). Multivariate analysis confirmed that enhanced TIMP‐3 expression was an independent factor for a favorable prognosis (P = 0.037). Conclusions TIMP‐3 expression status was significantly correlated with pathologic stage and nodal involvement, and was an independent prognostic factor in resected NSCLC. J. Surg. Oncol. 2007;95:250–257.

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