Prognostic significance of ALDH1A1-positive cancer stem cells in patients with locally advanced, metastasized head and neck squamous cell carcinoma

Aldehyde dehydrogenase 1 (ALDH1A1) has now been recognized as a cancer stem(-like) cells (CSCs) marker in various tumors including head and neck squamous cell carcinoma (HNSCC). The objective of this study was to examine the expression of ALDH1A1 in patients with locally advanced, metastasized HNSCC and to determine its prognostic value. Human papillomavirus genotypes and expression of ALDH1A1, Twist1, and p16 were analyzed in specimens of 81 patients with primary HNSCC and 49 lymph node metastases. Patient clinicopathologic and follow-up data were analyzed. Expression of ALDH1A1 was observed in 38 (46.9 %) of 81 primary tumors and 26 (53 %) of 49 lymph node metastases, respectively. Notably, the expression of ALDH1A1 was correlated significantly with poor tumor differentiation grade (p = 0.011). Interestingly, ALDH1A1 was observed co-expressed with Twist1 in primary tumor and lymph node metastases. Multivariate analysis showed that ALDH1A1 expression predicted poor prognosis in patients with HNSCC (p = 0.011) and the subgroup of oropharyngeal squamous cell carcinoma (p = 0.001). In the patient cohort with advanced, metastasized tumors, ALDH1A1 was identified as independent predictor of overall survival in both groups. Our results provide evidence for the prognostic value of ALDH1A1 as a CSC marker in patients with locally advanced, metastasized HNSCC.