• Na,K-ATPase;
  • sodium pump;
  • Na,K-ATPase α-subunit;
  • Na,K-ATPase β-subunit;
  • bladder cancer;
  • recurrence;
  • tissue microarray



The purpose of this study was to determine the clinical significance of Na,K-ATPase α- and β-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).


Na,K-ATPase α- and β-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.


Compared with the benign fields, the mean protein expression for both Na,K-ATPase α- and β-subunits were found to be decreased overall in in situ and invasive tumors, as well as in tumor-adjacent dysplastic fields. When Na,K-ATPase α- and β-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 α- and β-subunits, respectively). The authors also found that patients with high α- and low β-subunit expression had a high risk for early recurrence, whereas patients with a low α- and high β-subunit expression had a significantly longer median recurrence-free time (17 months and 125 months, respectively, log rank statistics P = 0.0005).


The results suggested that Na,K-ATPase α- and β-subunit expression levels may be useful predictors of clinical outcomes such as recurrence-free time of bladder cancer patients. Cancer 2003;97:1859–68. © 2003 American Cancer Society.

DOI 10.1002/cncr.11267