title: ALDH1-positive cancer stem-like cells are enriched in nodal metastases of oropharyngeal squamous cell carcinoma independent of HPV status.
abstract: Oropharyngeal squamous cell carcinoma (OSCC) is caused by high-risk (HR) human papillomavirus (HPV) or alcohol and tobacco abuse. Aldehyde dehydrogenase 1 (ALDH1) is a confirmed marker for cancer stem-like cells (CSCs) of OSCC responsible for therapy resistance, recurrence and metastasis. Associations between HR-HPV/p16, CSC frequency and clinicopathological parameters in patients with metastatic OSCC were investigated. In the present study, HPV genotypes and expression of ALDH1 and p16 was analyzed in 40 paired OSCC and metastases. A significant correlation between ALDH1 positivity with lower primary tumor differentiation grade (P=0.009) and higher nodal status (P=0.015) was noted. Compared to primary tumors, the proportion of ALDH1-expressing cells was significantly increased in metastases (P=0.012), while significantly fewer ALDH1-expressing cells were found in HR-HPV-DNA⁺/p16⁺ primary tumors (P=0.038) compared to HR-HPV-DNA⁻/p16⁻ primary tumors. Metastases showed no difference. ALDH1⁺ CSCs are detectable in OSCC and metastases. ALDH1 high-grade OSCC exhibits a more aggressive phenotype characterized by higher nodal classification and lower differentiation. This suggests a subpopulation contained in the ALDH1-positive OSCC cell pool able to complete the metastatic cascade and subsequently enriching in metastasis independent of tumor etiology and ALDH1 content.
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany.
authors.forename: Xu
authors.initials: X
authors.lastname: Qian
authors.forename: Steffen
authors.initials: S
authors.lastname: Wagner
authors.forename: Chenming
authors.initials: C
authors.lastname: Ma
authors.forename: Jens P
authors.initials: JP
authors.lastname: Klussmann
authors.forename: Michael
authors.initials: M
authors.lastname: Hummel
authors.forename: Andreas M
authors.initials: AM
authors.lastname: Kaufmann
authors.forename: Andreas E
authors.initials: AE
authors.lastname: Albers
mesh_terms: D000328:Adult; D000368:Aged; D000080924:Aldehyde Dehydrogenase 1 Family; D002294:Carcinoma, Squamous Cell / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology* / Q000821:virology; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism; D005260:Female; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D014411:Neoplastic Stem Cells / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology* / Q000821:virology; D009959:Oropharyngeal Neoplasms / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology* / Q000821:virology; D027383:Papillomaviridae / Q000302:isolation & purification; D030361:Papillomavirus Infections / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D050697:Retinal Dehydrogenase / Q000378:metabolism*
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; D007527:Isoenzymes; D000080924:Aldehyde Dehydrogenase 1 Family; C510223:ALDH1A1 protein, human; D050697:Retinal Dehydrogenase