Prognostic Significance of Reversion-Inducing Cysteine-Rich Protein With Kazal Motifs Expression in Resected Pathologic Stage IIIA N2 Non–Small-Cell Lung Cancer

Abstract

Reversion-inducing cysteine-rich protein with Kazal motifs (RECK) is a novel membrane-anchored matrix metalloproteinase inhibitor, and experimental studies have shown that RECK can suppress tumor progression through angiogenesis inhibition. We have already revealed that enhanced RECK expression is significantly correlated with a favorable prognosis in non-small-cell lung cancer (NSCLC). In this study, further analyses focused on pN2 disease were conducted to assess the clinical significance of RECK expression. A total of 118 patients with completely resected pathologic stage IIIA N2 NSCLC were retrospectively examined. RECK expression in the primary tumor, along with involved N2 nodes, was examined immunohistochemically. RECK expression in the primary tumor was strong in 53 patients (44.9%) and was weak in the other 65 patients. The 5-year survival rate of patients with RECK-strong tumor (42.9%) was significantly higher than that of patients with RECK-weak tumor (23.1%; P = .017). Reduced RECK expression significantly correlated with a poor prognosis for patients with a single N2 node involved (P = .019), but not for patients with multiple N2 nodes involved (P = .440). A multivariate analysis confirmed that reduced RECK expression was an independent and significant factor to predict a poor prognosis (P = .031). RECK expression in involved N2 nodes was significantly higher than in primary tumors (P < .001). RECK status was a novel prognostic factor in pathologic stage IIIA N2 NSCLC.