Immunohistochemical Ratio of α-3 and α-1 Subunits of Sodium Pump Correlates with Prostate Cancer Biochemical Recurrence: A Tissue Microarray Study
D Trudel, A Roussel-Jobin, B Tetu, Y Fradet, L Lacombe, H Hovington, M Njoya, T Mijatovic, R Kiss. Centre Hospitalier Universitaire de Québec, Québec, Canada; Université Libre de Bruxelles, Bruxelles, Belgium
Background: Sodium pump (Na+/K+ ATPase) is made of α and β-subunits. Expression of the α subunit is altered in many cancer types. Considering that Na+/K+ ATPase is the target of cardiotonic steroids such as digoxin, we hypothesized that the finding of an association between the expression of α-1 (SUα1) and α-3 (SUα3) subunits and prostate cancer (PCA) prognosis might have important therapeutic implications.
Design: Men included in the cohort were diagnosed with a pT3N0-2M0 PCA treated by radical prostatectomy. A tissue microarray was built from representative areas of prostate tumors and the percentage of cancer cells expressing SUα1 and SUα3 by immunohistochemistry was evaluated. Frequency tables with Pearson's correlations were built to evaluate the association between the expression levels of SUα1, SUα3, SUα3:SUα1 ratio and known PCA prognostic factors. Wald test from Cox regression model was used to measure the association between SUα1, SUα3, SUα3:SUα1 ratio and time to biochemical recurrence and death of any causes.
Results: Mean follow-up time of the 74 men included in the cohort was 13 years. Thirty-two biochemical recurrences and 8 deaths were observed. SUα1 expression level was inversely associated with Gleason score on biopsy (p = 0.0019). SUα3 and SUα3:SUα1 ratio were not associated with any known PCA prognostic factor. While no association with recurrence or death was found with SUα1 and SUα3 expression levels, the SUα3:SUα1 ratio was significantly associated with PCA biochemical recurrence (HR = 1.68, 95%CI [1.03; 2.74], Cox regression adjusted for initial serum prostate specific antigen level).
Conclusions: This study shows that, although SUα1 expression level is inversely associated with PCA Gleason score, SUα3:SUα1 ratio correlates with PCA biochemical recurrence. The ratio of sodium pump subunits expression appears as an interesting potential PCA marker that may lead to the development of new targeted therapies.
Category: Genitourinary (including renal tumors)
Monday, March 22, 2010 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 140, Monday Morning