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


METHODS
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.


RESULTS
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.


CONCLUSIONS
Our results provide evidence for the prognostic value of ALDH1A1 as a CSC marker in patients with locally advanced, metastasized HNSCC.
Department of Otolaryngology, Head and Neck Surgery, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, 12200, Berlin, Germany.
Xu
X
Qian
Steffen
S
Wagner
Chenming
C
Ma
Annekatrin
A
Coordes
Julia
J
Gekeler
Jens P
JP
Klussmann
Michael
M
Hummel
Andreas M
AM
Kaufmann
Andreas E
AE
Albers
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000444:Aldehyde Dehydrogenase / Q000378:metabolism*; D000080924:Aldehyde Dehydrogenase 1 Family; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis* / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D005260:Female; D006258:Head and Neck Neoplasms / Q000175:diagnosis* / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology; D009687:Nuclear Proteins / Q000378:metabolism; D011237:Predictive Value of Tests; D011379:Prognosis; D050697:Retinal Dehydrogenase; D000077195:Squamous Cell Carcinoma of Head and Neck; D016019:Survival Analysis; D051879:Twist-Related Protein 1 / Q000378:metabolism
D014408:Biomarkers, Tumor; D009687:Nuclear Proteins; C103173:TWIST1 protein, human; D051879:Twist-Related Protein 1; D000080924:Aldehyde Dehydrogenase 1 Family; D000444:Aldehyde Dehydrogenase; C510223:ALDH1A1 protein, human; D050697:Retinal Dehydrogenase