Role of ALDH1a and CD44 in transitional and squamous cell carcinomas of urinary bladder

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Abstract

Background

Urinary bladder cancer is a global and national health problem. The highest mortality rate worldwide occurs in Egyptian male population. There is increasing need to improve current therapeutic approaches to improve prognosis. Bladder tumors exhibit phenotypic and genotypic heterogeneity. Tumor-initiation, self-renewal, and resistance to treatment characterize cancer stem cells (CSCs). Urothelial CSCs cannot be isolated using a ‘one-marker-fits-all’ approach. Various marker combinations are better.

Aim

The aim of this work was to study the immunohistochemical expression of aldehyde dehydrogenase 1 family, member A1 (ALDH1a) and CD44 in bladder cancer and correlate them with clinicopathological parameters.

Materials and methods

The study included 60 archival cases (46 transitional and 14 squamous cell carcinoma cases) stained with ALDH1a and CD44s antibodies.

Results

ALDH1a was positive in 39.1% of transitional cell carcinoma (TCC) cases and in 57.1% of squamous cell carcinoma (SCC) cases. CD44 was positive in 80.4% of TCC cases and 100% of SCC cases. In TCC, ALDH1a and CD44 were associated with advanced stage (P=0.04 and 0.000, respectively). In SCC, ALDH1a was associated with high grade (P=0.007). CD44 was higher in cases that presented in early stage (P=0.03) and associated with bilharziasis (P=0.02). CD44 was inversely correlated to ALDH1a (r=−0.6, P=0.03) and was significantly higher in SCC (P=0.001).

Conclusion

ALDH1a expression was associated with unfavorable features such as advanced stage in TCC cases and high grade in SCC cases. ALDH1a+ cells constitute a subpopulation of CD44+ cells and might represent more primitive CSCs. Target therapy against ALDH1a could be effective, especially in advanced tumors. Target therapy against CD44 could be helpful for bladder SCC or TCC with squamous differentiation.

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