Cancer stem cell markers CD44 and ALDH1A1 are overexpressed in melanoma compared to non-melanoma skin tumors and confer aggressive tumor behavior

Introduction: Skin cancers, particularly melanoma, are initiated and maintained by a subpopulation of tumor cells expressing stemness markers that called cancer stem cells (CSCs). This study aimed to evaluate the expression levels and clinicopathological significance of putative CSC markers CD44 and ALDH1A1 in skin cancer patients. Methods: The expression levels of two putative CSC markers CD44 and ALDH1A1 were investigated in 107 skin cancer specimens including 58 (54%) basal cell carcinoma (BCC), 37 (35%) squamous cell carcinoma (SCC), and 12 (11%) melanoma using tissue microarray (TMA) technique. The correlation of expression levels of these markers and clinicopathological parameters was then analyzed. Results: The expression level of CD44 and ALDH1A1 was significantly higher in melanoma patients compared to SCC and BCC cases (P<0.001 and P=0.002, respectively). Higher level of CD44 expression was more often found in melanoma tumor cells with a higher rate of recurrence (P=0.029) and in SCC cases with ulceration (P=0.01), while there was no significant correlation between ALDH1A1 expression and other clinicopathological parameters. Similarly, co-expression of CD44 and ALDH1A1 markers (CD44high/ALDH1A1high) was significantly observed in melanoma samples (P<0.001). Conclusions: These findings suggest that CD44high/ALDH1A1high phenotype in melanoma and CD44high in SCC can be considered as candidates for targeted therapy of skin cancers aiming at CSCs.