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ALDH1 Expression in Bladder Cancer Correlates with Histopathologic Indicators of Poor Prognosis
Sammy E. Elsamra, MD, Andres Matoso, MD, Kamaljeet Singh, MD, Rosemarie Tavares, B.S., Lelia Noble, B.S., Joseph Renzulli, MD, George Haleblian, MD, Murray B. Resnick, MD, Li J. Wang, MD, Gyan Pareek, MD.
Warren Alpert Medical School of Brown University, Providence, RI, USA.

ALDH1 Expression in Bladder Cancer Correlates with Histopathologic Indicators of Poor Prognosis
Introduction and Objective:
Evidence has been accumulating to support the cancer stem cell hypothesis for solid tumors. Stem cells marker aldehyde dehydrogenase (ALDH)-1 expression has been detected 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. The objective of this study was to evaluate ALDH1 expression in bladder cancer samples and correlate with currently used histopathologic hallmarks of prognosis in patients with bladder and their clinical followup.
Design: Tissue microarrays were constructed with normal and tumor tissue samples from 81 endoscopic bladder resections and radical cystectomy specimens and immunohistochemistry for ALDH1 was performed (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, invasion, pathological stage, nuclear grade, and clinical followup were analyzed.
Result: Focal expression of ALDH1 was detected along the basal cells in 4% of normal tissue samples. Expression of ALDH1 in tumor samples and its relationship with depth of invasion is summarized in Table 1.

ALDH1 Expression in Bladder Cancer
ALDH1 expression
TotalStrong (%)Weak (%)Negative (%)
All cases8130 (36)12 (14)42 (50)
Non-invasive253 (12)5 (20)17 (68)
Invasion into lamina propria233 (13)1 (4)19 (83)
Invasion into muscularis propria and beyond3321 (64)6 (18)6 (18)

Strong expression of ALDH1 correlated with invasion into the muscularis propria and beyond when compared to non-invasive tumors and tumors invading the lamina propria (63.6 % vs. 12.5%; p<0.001). Regarding tumor differentiation, poorly differentiated tumors showed higher ALDH1 expression than tumors with papillary differentiation (65% vs. 21%; p=0.002). No correlation was seen with nuclear grade. Survival at 100 months in patients with strong expression of Aldh1 was 15% vs. 50% in patients with weak or negative ALDH1 expression. Stage matched survival analysis was not possible due to the size of the sample studied.
Conclusion: This is the first study to describe ALDH1 expression in bladder cancer and its correlation with histopathologic indicators of prognosis and clinical followup. Our results demonstrate that ALDH1 expression correlates with indicators of poor prognosis such as invasion into the muscularis propria and poorly differentiated tumors. Although our results suggest that Aldh1 strong correlates with overall shorter survival, a larger cohort of patients with a stage matched analysis is necessary to confirm this hypothesis.
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