Prognostic significance of heme oxygenase-1, S100 calcium-binding protein A4, and syndecan-1 expression in primary non-muscle-invasive bladder cancer.

Abstract

We investigated the prognostic significance of heme oxygenase-1 (HO-1), S100 calcium-binding protein A4 (S100A4), and syndecan-1 (SYND1) expression in patients with primary non-muscle-invasive bladder cancer (NMIBC). Immunohistochemical studies were performed on tissue specimens from 109 patients diagnosed with primary NMIBC following complete transurethral resection, with the expression dichotomized as negative/mild ("low") versus moderate/strong ("high") according to scores based on staining area and intensity. The effect of each biomarker on recurrence-free survival (RFS) and progression-free survival (PFS) was analyzed. The predictive accuracy for RFS and PFS in multivariate Cox regression models with or without (the baseline model) biomarkers was estimated using the Harrell concordance index. High HO-1, S100A4, and SYND1 expressions were observed in 33.0%, 36.7%, and 63.3% cases, respectively. High HO-1 and S100A4 expressions were significantly associated with various adverse pathological characteristics (high T stage and grade); SYND1 expression was inversely correlated with these characteristics (all, P < .05). In the baseline multivariate model, multifocality, intravesical therapy, and T stage were significant predictors for RFS, whereas intravesical therapy and T stage had marginal statistical significance in predicting PFS. In the multivariate model with the biomarkers, the 3 biomarkers were significant predictors for RFS; and HO-1 expression was a significant predictor for PFS. Addition of the 3 biomarkers to the baseline model significantly increased the predictive accuracy for RFS from 0.754 to 0.828 (P = .043). Our findings suggest that HO-1, S100A4, and SYND1 expressions have prognostic value in primary NMIBC; thus, their evaluation might be useful for determining treatment strategies.