The Expression and Prognostic Significance of RalA and RalB Expression in Bladder Cancer.
Steven C Smith, Matthew D Nitz, Alexander S Baras, Dan T Theodorescu. University of Michigan Health System, Ann Arbor; University of Virginia Health System, Charlottesville; University of Colorado, Aurora
Background: The Ral family of GTPases, including RalA and RalB, have been established as key mediators of cancer phenotypes in several tumors, while we have identified roles for both in models of metastatic progression of bladder cancer. Despite these findings, the expression of these GTPases has not been examined in human bladder tumor samples.
Design: A tissue microarray consisting of 145 quadruplicate cores of human bladder cancer cystectomy specimens (urothelial N=110, squamous N=22, adenocarcinoma N=7, other N=6), with paired staging and follow-up data, was stained for RalA and RalB using paralog-specific antibodies. Staining intensity was scored semiquantatively as low or high. Association between staining and clinicopathologic parameters was tested by the chi-squared test and Gehan-Wilcoxon-Breslow tests, as appropriate.
Results: RalA and RalB variably stained both cytoplasmic and membrane compartments of tumor cells, and were not strongly correlated (P=0.10). Neither RalA nor RalB were significantly associated with gender, pT, pN, LVSI, or concomitant CIS. RalB, but not RalA, was significantly associated with histologic type of bladder cancer (P=0.009), with strong staining in squamous carcinomas and adenocarcinomas. RalA, but not RalB, staining was significantly associated with decreased survival post cystectomy in urothelial carcinomas (P=0.04), but not in non-urothelial tumors (P=0.37).
Conclusions: While the Ral GTPase activity may be regulated by mechanisms other than expression, our findings associate overexpression of RalA with decreased patient survival, supportive of the relevance of prior experimental findings to human disease. Association of RalB with non-urothelial histology was unexpected and suggests investigation in this area.
Category: Genitourinary (including renal tumors)
Tuesday, March 1, 2011 9:30 AM
Poster Session III # 173, Tuesday Morning