Stem Cell Marker ALDH1 Expression Correlates with Unfavorable Prognosis in Prostate Cancer
A Matoso, R Tavares, L Noble, Y Zhang, R Jacob, J Renzulli, G Pareek, G Haleblian, MB Resnick, LJ Wang. Brown University and Rhode Island Hospital, Providence, RI
Background: Aldehyde dehydrogenase (ALDH) 1 is an enzyme that is ubiquitously expressed and catalyzes the oxidation of aldehydes to their carboxylic forms. ALDH1 activity has been used to identify stem-like subset of cells in human and murine hematopoietic and solid tumors. Recent studies demonstrated that increased ALDH1 expression correlates with poor clinical outcome in breast cancer but favorable prognosis in ovarian cancer. We hypothesized that the level of ALDH1 expression may correlate with the clinical outcome of patients with prostate cancer.
Design: Immunohistochemical staining of ALDH1 expression was analyzed in 175 radical prostatectomy specimens using tissue microarrays (clone 44/ALDH; 1:400 dilution; BD Biosciences). Results were scored using a quantitative system that assigned 1-4 points for extent and for intensity of staining. A total score of 5 or higher was considered strong and 4 or lower was considered weak. The associations between the expression of ALDH1, pathological stage, Gleason score and overall survival time were analyzed.
Results: Focal expression of ALDH1 was noticed in the cytoplasm of non-tumoral prostatic acini in 5% of the cases studied. Weak staining was also noted in stromal cells and blood vessel walls. Elevated ALDH1 expression was found in 39.6% of all tumor samples and correlated with Gleason score, 26.5% positive in Gleason ≤6, and 55.3% positive in Gleason ≥7 (p<0.001)). Strong ALDH1 expression also correlated with higher pathological stage (pT2c or higher; 46% vs. 28%; P=0.04). As expected, Gleason score and stage inversely correlated with overall survival. Patients with Gleason score ≥7 and strong ALDH1 expression had a shorter overall survival time than patients with Gleason score ≥7 and weak ALDH1 expression (P=0.03). Although not statistically significant, patients with Gleason score ≤ 6 and strong ALDH1 expression also had a tendency towards shorter survival time than patients with Gleason score ≤ 6 and weak ALDH1 expression.
Conclusions: This is the first study to describe ALDH1 expression and to determine its prognostic significance in prostate cancer. Our results demonstrate that ALDH1 expression correlates with high Gleason score, higher stage at diagnosis and shorter overall survival time.
Category: Genitourinary (including renal tumors)
Monday, March 22, 2010 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 130, Monday Morning