ALDH1A1 as a Marker of Stem Cells in Prostate Cancer: Correlation with Gleason Scores & Tumor Stage and Relevance for Patient Outcome.
Ryan Bremer, David Tacha. Biocare Medical, LLC, Concord, CA
Background: Mounting evidence supports the role of cancer stem cells (CSCs) in the recurrence and metastasis of several malignancies, including prostate cancer (CaP). Markers of CSCs potentially offer valuable diagnostic tools and predictors of disease progression. ALDH1A1, a member of the aldehyde dehydrogenase (ALDH) family of enzymes, has been shown to be a useful marker of CSCs. Expression of ALDH1A1 is associated with poor patient outcomes in several cancers, including breast, lung, and bladder. Additionally, in prostate cancer patients, ALDH1A1 expression has recently been shown to be associated with higher Gleason sums and advanced tumor stage. Most importantly, ALDH1A1 expression is a predictor of prostate cancer patient outcomes. Patients with high expression of ALDH1A1 have significantly reduced overall and cancer-specific survival rates compared to those with low expression of ALDH1A1 (P=0.0093 and P=0.0017, respectively).
Design: Tissue micro-arrays, with known Gleason sums and TNM staging, containing 169 samples of prostate adenocarcinoma were evaluated for expression of ALDH1A1 by immunohistochemistry, using a rabbit monoclonal antibody for ALDH1A1. Positive ALDH1A1 staining was determined for each sample and classified as either “Negative or Low” (<10% of cells staining) or “High” (>10%) expression.
Results: 37 of 169 (22%) CaP samples exhibited high expression of ALDH1A1. Samples with Gleason sums ≥8 had high expression of ALDH1A1 in 21 of 60 (35%) cases, whereas those with an intermediate Gleason sum of 7 showed high expression in 8 of 34 (19%) cases, and only 8 of 59 (12%) cases with Gleason sums ≤6 exhibited high expression of ALDH1A1.
|Gleason Sum||Neg or Low||High||Total||% High Expression|