title: Characterization and clinical relevance of ALDHbright populations in prostate cancer.
abstract: OBJECTIVE
  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 ALDH activity (ALDH(bright)) in primary prostate cancer specimens has not been shown so far. We investigated the presence, phenotype, and clinical significance of ALDH(bright) populations in clinical prostate cancer specimens.
  
  
  METHODS
  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-specific expression and prognostic significance were assessed by staining two tissue microarrays that included 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 = 39) and were mainly included within the EpCAM((+)) and Trop2((+)) cell populations. Although several ALDH isoforms were 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 = 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 = 0.02) in hormone-naïve patients.
  
  
  CONCLUSIONS
  Our data indicate that ALDH contributes to the identification of subsets of prostate cancer cells of potentially high clinical relevance.
authors: Authors' Affiliations: ICFS, Departments of Surgery and Biomedicine, Department of Urology, Institute for Pathology, Basel University Hospital; Division of Urology, St Claraspital, Basel; and Department of Urology, University of Bern, Bern, Switzerland.
authors: Clémentine
authors: C
authors: Le Magnen
authors: Lukas
authors: L
authors: Bubendorf
authors: Cyrill A
authors: CA
authors: Rentsch
authors: Chantal
authors: C
authors: Mengus
authors: Joel
authors: J
authors: Gsponer
authors: Tobias
authors: T
authors: Zellweger
authors: Malte
authors: M
authors: Rieken
authors: George N
authors: GN
authors: Thalmann
authors: Marco G
authors: MG
authors: Cecchini
authors: Markus
authors: M
authors: Germann
authors: Alexander
authors: A
authors: Bachmann
authors: Stephen
authors: S
authors: Wyler
authors: Michael
authors: M
authors: Heberer
authors: Giulio C
authors: GC
authors: Spagnoli
mesh_terms: D000444:Aldehyde Dehydrogenase / Q000235:genetics / Q000378:metabolism*; D000080924:Aldehyde Dehydrogenase 1 Family; D014408:Biomarkers, Tumor / Q000378:metabolism; D045744:Cell Line, Tumor; D004847:Epithelial Cells / Q000378:metabolism; D005434:Flow Cytometry; D015870:Gene Expression; D006801:Humans; D016130:Immunophenotyping; D007527:Isoenzymes; D008297:Male; D010641:Phenotype; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality; D021381:Protein Transport; D050697:Retinal Dehydrogenase
chemical_list: D014408:Biomarkers, Tumor; D007527:Isoenzymes; D000080924:Aldehyde Dehydrogenase 1 Family; D000444:Aldehyde Dehydrogenase; C510223:ALDH1A1 protein, human; D050697:Retinal Dehydrogenase