Abstract
Introduction: Matrix metalloproteinase-9 (MMP-9) plays an essential role in degrading extracellular matrix and this contributes to invasiveness and metastatic potential of tumor cells. The associations of MMP-9 expression with prognosis in various cancers have been reported in previous studies but there is a controversy about the prognostic role of MMP-9. In this study, we evaluated the prognostic value of MMP-9 in patients with extrahepatic bile duct (EHBD) cancer undergoing surgical resection and adjuvant radiotherapy. Methods: Between January 2000 and August 2006, 66 patients who underwent R0 resection and following adjuvant radiotherapy for EHBD cancer were enrolled in this study. All patients received radiotherapy with median dose of 40 Gy (range, 40-56Gy) and 61 patients received concomitant fluoropyrimidine chemotherapy. Tissue microarray was constructed from surgical specimens of enrolled patients and immunohistochemical staining was undertaken to evaluate the expression of MMP-9. Results: 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 rate were 50.8% versus 86.5% (P = 0.0281), and 23.3% versus 68.1% (P = 0.0087) in patients with low and high expression of MMP-9, respectively. Among the clinicopathologic factors, hilar tumor location was associated with DMFS and OS (p = 0.0292 and p = 0.0003, respectively). Nodal stage and histologic differentiation showed significant association with DMFS (p = 0.0277 and p = 0.0060, respectively). On multivariate analysis for OS, hilar tumor location was the only significant prognostic factor (p = 0.0021), while MMP-9 expression showed marginal significance (p = 0.0633). Conclusion: MMP-9 expression is a favorable prognostic factor for predicting LRRFS and OS in patients with EHBD cancer after surgical resection and adjuvant radiotherapy.
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