Different Immunohistochemical Expression of CD44v6 and ALDH1 in Prostate Cancer before and after Androgen Deprivation Therapy
SA Umar, M Fiorentino, C Magi-Galluzzi, D Bailey, C Fiore, R Montironi, M Loda. Brigham and Women's Hospital, Boston, MA; Dana-Farber Cancer Institute, Boston, MA; Cleveland Clinic Foundation, Cleveland, OH; University of Ancona, Ancona, Italy
Background: According to the hierarchical or stem cell model of cancer, only a relatively small subpopulation of stem cells is capable of initiating tumor growth. If this subpopulation of stem cells survives nonsurgical therapies such as anti-androgen receptor therapy, radiation- or chemo-therapy, then there is opportunity for tumor to regrow. Aldehyde dehydrogense 1 (ALDH1), a stem cell marker, is present in the secretory cells of both normal and cancer cells. CD44v6, a splice variant of a protein involved in cell adhesion and signaling, is present on the luminal surfaces of prostatic basal cells. The aim of this study was to determine the pattern of ALDH1 and CD44v6 prevalence after neoadjuvant hormone blockade / androgen ablation therapy in prostate adenocarcinoma as putative markers of cancer stem cells (CSC).
Design: 65 cases of prostate core biopsies containing prostatic adenocarcinoma (38 cases with Gleason grade 3+3=6, 15 cases with Gleason grade 3+4=7, 7 cases of Gleason grade 4+3=7, and 5 cases with Gleason grade 8) were identified. Each patient was treated by radical prostatectomy following neoadjuvant hormone blockade for 3 to 6 months. Diagnostic biopsies as well as the corresponding prostatectomy specimens were stained with CSC markers ALDH1 and CD44v6.
Results: In the prostate core biopsies before therapy, ALDH1 was positive in 68% of cases (44 of 65) while CD44v6 was positive in 12% (8 of 65). Four cases disclosed 8% of cells with co-localization. Following hormonal treatment, ALDH1 decreased and/or was unchanged in 89% (58 of 65), and enriched in 11% (7 of 65) of cases. In contrast, CD44v6 was enriched in 54% (35 of 65), and decreased in 5% (3 of 65) of cases. Thirteen cases disclosed 2% of cells with co-localization. The decrease in ALDH1 and enrichment in CD44v6 following hormone ablation therapy were both significant (p<0.001).
Conclusions: The putative CSC markers CD44vs and ALDH1 behave discordantly following neoadjuvant hormone blockade / androgen ablation therapy. The enrichment in CD44v6 suggests that CSC probably reside in the basal cell compartment. Additional stem cell markers are needed to more accurately define this population of cells.
Category: Genitourinary (including renal tumors)
Wednesday, March 11, 2009 9:30 AM
Poster Session V # 101, Wednesday Morning