Na,K-Adenosine Triphosphatase α₁-Subunit Predicts Survival of Renal Clear Cell Carcinoma

Purpose: Na,K-adenosine triphosphatase, which is composed of a catalytic α-subunit and a regulatory β-subunit, generates an electrochemical gradient across the plasma membrane. Previous studies demonstrated altered Na,K-adenosine triphosphatase subunit expression in renal clear cell carcinoma and an association of subunit levels with the prediction of recurrent bladder cancer. We determined the clinical association of protein expression patterns of the Na,K-adenosine triphosphatase α₁ and β₁-subunits in renal clear cell carcinoma using tissue microarrays with linked clinicopathological data. Materials and Methods: The UCLA kidney cancer tissue microarray was used to investigate the protein expression of Na,K-adenosine triphosphatase α₁ and β₁-subunits by immunohistochemistry in 342 patients with renal clear cell carcinoma who were treated with radical nephrectomy. Of these patients clinical outcomes studies were performed in 317. The resultant expression reactivity was correlated with clinicopathological variables. Results: We found that the α₁-subunit was a significant and independent predictor of disease specific death from renal clear cell carcinoma on multivariate Cox proportional hazards analysis that included established prognostic factors Eastern Cooperative Oncology Group performance status, pT status, metastasis status and tumor grade. Significance was found when examining all patients with clear cell renal cell carcinoma as well as patient substrata with low or high grade tumors and localized or metastatic disease, suggesting that the Na,K-adenosine triphosphatase α₁-subunit could be used as a new prognosticator for disease specific death from renal clear cell carcinoma. Conclusions: These results suggest that Na,K-adenosine triphosphatase α₁-subunit expression patterns may be a useful clinical prognosticator for renal clear cell carcinoma. The Na,K-adenosine triphosphatase β₁-subunit was not found to be a useful prognosticator in this setting.