[886] Expression of Putative Stem Cell Markers ALDH1 and CD133 in Urothelial Carcinoma of the Bladder.

Andres Matoso, Katherine T Sciandra, Sammy Elsamra, Kamaljeet Singh, Joseph Renzulli, Rafik Jacob, Rosemary Tavares, George Haleblian, Lelia Noble, Gyan Pareek, Murray B Resnick, Li J Wang. Rhode Island Hospital/Brown University, Providence

Background: Expression of the stem cells markers aldehyde dehydrogenase-1 (ALDH1) and CD133 have been detected in hematopoietic and solid tumors. This is the first study that evaluates the expression of ALDH1 and CD133 in bladder cancer and their associations with pathological stage and patient followup.
Design: Tissue microarrays were constructed with normal and tumor samples from 81 endoscopic bladder resections and cystectomy specimens. Immunohistochemistry for ALDH1 (1:400 dilution; clone44 BD Biosciences) and CD133 (dilution 1:200; ab19898 Abcam) was performed and scored using a quantitative system that assigned 1-4 points for extent and for intensity. A total score of 5 or higher was considered strong and 4 or lower weak.
Results: Normal urothelium expressed ALDH1 along the basal layer in 4% of samples while CD133 expression was present in the umbrella cells in 13 % of cases. Expression of ALDH1 and CD133 in tumors and its relationship with depth of invasion is summarized in Table 1.

Immunohistochemistry Results
  StrongWeakNegative
 TotalAldh1CD133Aldh1CD133Aldh1CD133
All cases81(100)28 (35)0(0)12 (15)22(27)41 (50)59(73)
Non-invasive25(30)4 (16)0(0)5 (20)6(24)16 (64)19(76)
Invasion into lamina propria23(28)3 (13)0(0)1 (4)8(35)19 (83)15(65)
Invasion into muscularis propria and beyond33(40)21 (64)0(0)6 (18)8(24)6 (18)25(76)


Strong ALDH1 expression correlated with muscularis propria invasion when compared to non-invasive tumors and tumors invading the lamina propria (63.6 % vs. 12.5%; p<0.001). CD133 expression was weaker and more focal and there was no correlation with invasion into lamina propria or muscle. Among non-invasive tumors, expression of ALDH1 was detected in 30% (6/20) of high grade and 60% (3/5) of low grade tumors; expression of CD133 was present in 25% (5/20) of high grade and 20% (1/5) of low grade tumors indicating a lack of correlation with tumor grade for both markers. Survival at 100 months in patients with strong expression of ALDH1 was 15% vs. 50% in patients with weak or negative ALDH1 expression.
Conclusions: Our results demonstrate that expression of ALDH1, but not CD133, correlates with invasion into the muscularis propria. Although our results suggest that strong expression of ALDH1 correlates with overall shorter survival, a larger cohort of patients with a stage matched analysis is necessary to confirm this hypothesis.
Category: Genitourinary (including renal tumors)

Tuesday, March 1, 2011 9:30 AM

Poster Session III # 182, Tuesday Morning

 

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