ALDH1 in Combination with CD44 as Putative Cancer Stem Cell Markers are Correlated with Poor Prognosis in Urothelial Carcinoma of the Urinary Bladder

Background: The aldehyde dehydrogenase 1 family member A1 (ALDH1A1) is one of the promising markersfor identifying cancer stem cells in many cancer types, along with other markers including CD44. The aim ofthe present study was to evaluate the expression and clinical significance of putative cancer stem cell markers,CD44 and ALDH1A1, in a series of urothelial carcinomas of urinary bladder (UCUB) by tissue microarray(TMA). Materials and
Methods: A total of 159 Urothelial Carcinomas (UC) including 96 (60%) low gradeand 63 (40%) high grade carcinomas were immunohistochemically examined for the expression of CD44 andALDH1A1. Correlations of the relative expression of these markers with clinicopathological parameters werealso assessed.
Results: High level expression of ALDH1A1 was found in 16% (25/159) of bladder UC which wassignificantly correlated with increased tumor size (p value=0.002), high grade (p value<0.001), pathologic stage(T1, p value=0.007 and T2, p value<0.001) and increased rate of recurrence (p value=0.013). A high level of CD44expression was found in 43% (68/159) of cases, being positively correlated with histologic grade (p value=0.032)and recurrence (p value=0.039).
Conclusions: Taken together, our results showed that ALDH1 was concurrentlyexpressed in a fraction of CD44+ tumors and its expression correlated with poor prognosis in UCs. ALDH1A1could be an ideal marker for targeted therapy of UCs in combination with conventional therapies, particularlyin patients with high grade carcinomas. These findings indicate that cells expressing ALDH1A1 along with CD44can be a potential therapeutic target in bladder carcinomas.