Expression of ALDH1A1 and CD44 in primary head and neck squamous cell carcinoma and their value for carcinogenesis, tumor progression and cancer stem cell identification.

ABSTRACT

In head and neck squamous cell carcinoma (HNSCC), aldehyde dehydrogenase 1 family, member A1 (ALDH1A1) and hyaluronan receptor cluster of differentiation 44 (CD44) are often used as cancer stem cell (CSC) markers. The aim of the present study was to examine the relevance of these proteins for HNSCC in general and for the identification of CSCs. Tumors from 48 patients with primary HNSCC were analyzed for the expression of ALDH1A1 and CD44. Additionally, the association of the proteins with the proliferation rate and epidermal growth factor receptor (EGFR) expression was analyzed. ALDH1A1 was expressed in 54.2% of the carcinoma samples while CD44 was expressed in 89.6% of the carcinoma samples. Most notably, these proteins were often not expressed exclusively in a subpopulation, but also in the majority of tumor cells (ALDH1A1 30.8% of ALDH1A1+ tumors; CD44 65.1% of CD44+ tumors). Furthermore, patients with ALDH1A1+ tumors exhibited worse survival rates. CD44 and EGFR expression patterns were overlapping within the tumors and the expression rates were significantly connected. Ki-67+ tumor cells often expressed CD44. ALDH1A1 and CD44 expression patterns only partly overlapped. Consequently, ALDH1A1 and CD44 play significant roles in carcinogenesis and tumor progression. Within the present study, CD44 appeared to interact with EGFR and was more often expressed in primary HNSCC than the marker ALDH1A1. However, ALDH1A1 was a better marker to define a subpopulation of tumor cells. Finally, neither ALDH1A1 nor CD44, alone or combined, were sufficient to determine the CSC population in HNSCC.