Analysis of the Na,K-ATPase alpha- and beta-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 invasive tumors, as well as in tumor-adjacent dysplastic fields. When Na,K-ATPase 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.
Espineda
Cromwell
C
Department of Pathology and Laboratory Medicine, University of California-Los Angeles, 90095, USA.
Seligson
David B
DB
James Ball
William
W
Rao
JianYu
J
Palotie
Aarno
A
Horvath
Steve
S
Huang
Yunda
Y
Shi
Tao
T
Rajasekaran
Ayyappan K
AK
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002295:Carcinoma, Transitional Cell / Q000737:chemistry / Q000201:enzymology* / Q000473:pathology; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D007527:Isoenzymes; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000737:chemistry / Q000201:enzymology* / Q000473:pathology; D011379:Prognosis; D012189:Retrospective Studies; D000254:Sodium-Potassium-Exchanging ATPase / Q000032:analysis*; D015996:Survival Rate; D001749:Urinary Bladder Neoplasms / Q000737:chemistry / Q000201:enzymology* / Q000473:pathology
D007527:Isoenzymes; D000254:Sodium-Potassium-Exchanging ATPase