SIU 2017: Relation of ALDH1a and CD44 with Clinicopathological Factors in Transitional and Squamous Cell Carcinomas of Urinary Bladder

Lisbon, Portugal (UroToday.com) Cancer stem cells, usually representing a small 1-2% of the tumor volume, may be resistant to traditional therapy and may be a source of treatment resistant and disease progression. There are various CSC markers that are being evaluated for association with CSC presence and subsequently disease aggressiveness and treatment response. ALDH1a and CD44 are two such markers of CSC.

In this study, the authors examine the IHC expression of these two CSC markers and their correlation with clinicopathologic features. Again, this is not an examination of causation, but only association. This is also a cross-sectional assessment, and does not follow these patients over time.

They examined 60 cases of archived pathology (46 urothelial, 14 SCC of the bladder). Specimens were obtained either from TURBT or RC, and none of these patients received prior therapy – all received primary TURBT or RC as treatment. Expression was classified as positive if any cells demonstrated cytoplasmic staining of ALDH1a or membranous staining for CD44. 

In the patients with urothelial malignancy, the expression of ALDH1a and CD44 were higher in patients with MIBC compared to NMIBC. ALDH1a was positive in 39% of urothelial cancer. CD44 was positive in 80% of urothelial cancer. 

In patients with SCC of the bladder, the expression of ALDH1a was higher in MIBC. However, all patients had CD44 expression, so no comparison was able. ALDH1a expression was expressed in 57% of patients. 

In urothelial cancer, both were associated with advanced stage. In SCC, ALDH1a was associated with high grade disease. CD44 was higher in cases that presented with early stage disease and was associated with bilharzial SCC. 

The authors suggest targeted therapy against ALDH1a in advanced disease. However, there is little evidence of causation – while there is an association, there is nothing to suggest that targeting this molecule, which is a marker of CSC, will result in treatment effect. More basic science modeling is required prior to clinical treatment.

Written by: Fouad Zanaty 

Written by: Thenappan Chandrasekar, MD, Clinical Fellow, University of Toronto, twitter: @tchandra_uromd, at the 37th Congress of Société Internationale d’Urologie - October 19-22, 2017- Lisbon, Portugal