Differential expression of MMP and uPA systems and prognostic relevance of their expression in esophageal squamous cell carcinoma

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Abstract
Matrix metalloproteinase (MMP) is critical for carcinoma progression. In our study, we evaluated the prognostic significance of the major MMP family such as MMP‐3, MMP‐9, MMP‐11 and MT1‐MMP at the mRNA in 44 esophageal squamous cell carcinoma (ESCC) that were previously characterized for MMP‐7, MMP‐1 and MMP‐2, and their relation to urokinase system (uPA and uPAR). MT1‐MMP, MMP‐11 and MMP‐2 expressions are closely associated with each other, while MMP‐9 and uPAR expressions are inversely associated with the former group. There is no MMP related to clinicopathological factors; however, patients with high MT1‐MMP could show worse prognosis, as compared to those with low MT1‐MMP expression (p=0.01), as well as MMP‐11 did (p=0.02). Both MMP showed clear expression of carcinoma cells by immunohistochemistry. In patients with high MT1‐MMP, recurrence was more prominent (23/26: 88.5%) than those with low MT1‐MMP (7/18: 38.9%) (p=0.0016). In the 20 cases who died within 3 years, all 15 cases with high MT1‐MMP showed initial recurrence of distant metastasis, and the other 5 cases with low MT1‐MMP showed locoregional recurrence (p=0.000064). These results could indicate that there is a relevant mechanism of associated expression of clinically significant MMP and that among them, MT1‐MMP plays the most critical role in ESCC progression.