Characterization and Clinical Relevance of ALDH bright Populations in Prostate Cancer

Purpose: High aldehyde dehydrogenase (ALDH) has been suggested to selectively mark cells with high tumorigenic potential in established prostate cancer cell lines. However, the existence of cells with high ALDHactivity(ALDH bright )inprimaryprostatecancerspecimenshasnotbeenshownsofar.Weinvestigated the presence, phenotype, and clinical significance of ALDH bright populations in clinical prostate cancer specimens. Experimental Design: We used ALDEFLUOR technology and fluorescence-activated cell-sorting (FACS) staining to identify and characterize ALDH bright populations in cells freshly isolated from clinical prostate cancer specimens. Expression of genes encoding ALDH-specific isoforms was evaluated by quantitative real- time PCR in normal prostate, benign prostatic hyperplasia (BPH), and prostate cancer tissues. ALDH1A1- specificexpressionandprognosticsignificancewereassessedbystainingtwotissuemicroarraysthatincluded more than 500 samples of BPH, prostatic intraepithelial neoplasia (PIN), and multistage prostate cancer. Results: ALDH bright cells were detectable in freshly excised prostate cancer specimens (n ¼ 39) and were mainlyincludedwithintheEpCAM (þ) andTrop2 (þ) cellpopulations.AlthoughseveralALDHisoformswere expressed to high extents in prostate cancer, only ALDH1A1 gene expression significantly correlated with ALDH activity (P < 0.01) and was increased in cancers with high Gleason scores (P ¼ 0.03). Most importantly, ALDH1A1 protein was expressed significantly more frequently and at higher levels in advanced-stage than in low-stage prostate cancer and BPH. Notably, ALDH1A1 positivity was associated with poor survival (P ¼ 0.02) in hormone-na€ � ve patients. Conclusions: Our data indicate that ALDH contributes to the identification of subsets of prostate cancer cells of potentially high clinical relevance. Clin Cancer Res; 1-11. � 2013 AACR.