High expression of MMP-9 is associated with better prognosis in extrahepatic bile duct cancer patients

Purpose: To evaluate the prognostic value of matrix metalloproteinase-9 (MMP-9) in patients with extrahepatic bile duct (EHBD) cancer undergoing surgical resection and adjuvant radiotherapy. Methods: Between January 2000 and August 2006, patients who underwent complete resection followed by adjuvant radiotherapy for EHBD cancer were enrolled in this study. The expression of MMP-9 was assessed with immunohistochemical staining. The prognostic values of the MMP-9 expression and other clinicopathologic factors were evaluated in univariate and multivariate analyses. Results: Sixty-six patients were included in this study. All received radiotherapy with a median dose of 40 Gy (range, 40–56), and 61 patients received concomitant fluoropyrimidine chemotherapy. MMP-9 was highly expressed in 33 patients (50.0%). MMP-9 expression was significantly associated with locoregional recurrence-free survival (LRRFS) and overall survival (OS) but not with distant metastasis-free survival (DMFS). The 5-year LRRFS and OS rates were 50.8% versus 86.5% (p =.0281), and 23.3% versus 68.1% (p =.0087) in patients with low and high expression of MMP-9, respectively. Among the clinicopathologic factors, tumor location was associated with DMFS and OS (p =.0292 and.0003, respectively). Nodal stage and histologic differentiation showed significant association with DMFS (p =.0277 and.0060, respectively). Based on multivariate analysis for OS, tumor location was the only significant prognostic factor (p =.0021), while MMP-9 expression showed marginal significance (p =.0633). Conclusion: MMP-9 expression is a useful prognostic factor for predicting LRRFS and OS in patients with EHBD cancer after surgical resection and adjuvant radiotherapy.