Clinical significance and prognostic value of S100A4 and matrix metalloproteinase-14 in patients with organ-confined bladder cancer.

Various therapeutic modalities are available for treatment of bladder cancer, and their effectiveness and patient outcome often depend on cancer cell invasiveness. However, the mechanisms underlying the early steps of bladder cancer cell invasion remain unknown. This study aimed to clarify the relationships between S100A4 expression and bladder cancer invasion of surrounding muscles, prognosis and expression of matrix metalloproteinase (MMP)-14 in patients with organ-confined bladder cancer. S100A4 and MMP-14 expression was analyzed in 85 cases of organ-confined (pTa, pT1 and pT2) bladder cancer using immunohistochemical technique. The expression levels were compared among the pTa, pT1 and pT2 tumors. In addition, the predictive values of S100A4 or MMP-14 expression for muscle invasion, metastasis and survival were investigated, as was the possible correlation between the expression of the two proteins. The proportion of S100A4-positive cancer cells in pT2 tumors (53%) was significantly higher (p<0.001) than in pTa (38.7%) or pT1 (40.9%) tumors; there was no difference between pTa and pT1. The results were similar for MMP-14 expression, which was significantly correlated with S100A4 expression (r=0.360, p<0.001). S100A4 expression predicted metastasis-free survival (p=0.009), but not cause-specific survival. The results implicated S100A4 in the early steps of muscle invasion via MMP-14, but not for mucosal invasion. S100A4 is therefore a potential therapeutic target for bladder cancer, and its expression is a risk factor for muscle invasion in patients with superficial tumors. In addition, S100A4 expression may be a useful prognostic factor for metastasis in patients with organ-confined bladder cancer.