Analysis of the Na,K-ATPase α- and β-subunit expression profiles of bladder cancer using tissue microarrays

BACKGROUND. The purpose of this study was to determine the clinical significance of Na,K-ATPase alpha- and beta-subunit expression in a histopathologically well-characterized group of patients representing a wide spectrum of tumor grades and disease stages with transitional cell carcinomas (TCC). METHODS. Na,K-ATPase alpha- and beta-subunit protein expression patterns were analyzed using immunohistochemistry on urothelial cancer tissue microarrays (TMA) of 146 patients diagnosed with urothelial carcinoma. For each subunit, the maximum staining intensity and the percentage of positive cells staining at the maximal intensity were analyzed. RESULTS. Compared with the benign fields, the mean protein expression for both Na,K-ATPase alpha- and beta-subunits were found to be decreased overall in in situ and as well as in tumor-adjacent dysplastic fields. When Na,K-ATPase invasive tumors, alpha- and beta-subunit expression levels were dichotomized into distinct groups, they were both found to be significant predictors of recurrence risk in multivariate logistic regression analysis (P = 0.0062, odds ratio [OR] = 2.6 and P = 0.013, OR = 0.43, for Na,K-ATPase alpha- and beta-subunits, respectively). The authors also found that patients with high alpha- and low beta-subunit expression had a high risk for early recurrence, whereas patients with a low alpha- and high beta-subunit expression had a significantly longer median recurrence-free time (17 months and 125 months, respectively, log rank statistics P = 0.0005). CONCLUSIONS. The results suggested that Na,K-ATPase alpha- and beta-subunit expression levels may be useful predictors of clinical outcomes such as recurrence-free time of bladder cancer patients. (C) 2003 American Cancer Society.