Aldehyde Dehydrogenase Class 1 (ALDH1) Expression Is Associated with Disease Outcome in Prostatic Adenocarcinomas (PAC)
T Nazeer, KD Linos, BVS Kallakury, HAG Fisher, BM Mian, CE Sheehan, JS Ross. Albany Medical College, Albany, NY, 12208; Georgetown University Hospital, Washington, DC
Background: ALDH1 catalyzes the oxidation of intracellular aldehydes involved in cell differentiation, response to oxidative stress and drug resistance. ALDH1 is also expressed in adult stem cells in both normal tissues and a variety of epithelial malignancies including carcinomas of the breast, lung, head and neck and ovary. The prognostic significance of ALDH1 expression in PAC has not been previously studied.
Design: Formalin-fixed, paraffin embedded sections from 154 PAC were immunostained by automated methods (Ventana Medical Systems, Inc., Tucson, AZ) using mouse monoclonal ALDH1 (clone 44/ALDH; BD Biosciences, San Jose, CA). Cytoplasmic immunoreactivity was semi quantitatively assessed in the tumor for all cases. Scoring was based on staining intensity and percentage of stained tumor cells. Results were correlated with clinicopathologic variables.
Results: Cytoplasmic ALDH1 over-expression was observed in 81/154 (53%) of PAC and correlated with high tumor grade [65% HG vs 43% LG, p=0.007], advanced stage [66% advanced vs 44% early, p=0.006], and biochemical disease recurrence [62% recur vs 45% non-recur, p=0.049]. On multivariate analysis, high tumor grade and advanced tumor stage independently predicted overall survival.
Conclusions: Over-expression of ALDH1 in PAC is associated with adverse prognostic factors and predicts disease relapse after primary therapy. Further study of this putative cancer stem cell marker in PAC appears warranted.
Category: Genitourinary (including renal tumors)
Wednesday, March 24, 2010 1:00 PM
Poster Session VI # 114, Wednesday Afternoon