title: Putative cancer stem cell marker expression in oral epithelial dysplasia and squamous cell carcinoma.
abstract: Multifactorial conditions underlie progression of potentially malignant oral lesions (PMOL) to oral squamous cell carcinoma (OSCC) and there is currently need for better prediction of malignant transformation. The hypothesised existence of cancer stem cells in dysplastic oral tissues provides the potential for more informed assessment of PMOL progression. Semi-quantitative immunohistochemical assessment of four putative cancer stem cell markers (CD24, CD44, CD271 and ALDH1) was conducted with a training cohort of 107 patient biopsies to establish clinically applicable score threshold values that were subsequently applied to a blind diagnosis in an independent validation cohort of 278 biopsies. Stain intensity scores for ALDH1, CD24 and CD44, but not CD271 were greater for OSCC than normal tissues. The intensity of ALDH1 and CD24 immunostaining correlated with increased oral epithelial disease severity, and CD24 was effective in distinguishing OSCC from non-malignant tissues, correctly diagnosing 71% of OSCC cases in the validation cohort. Importantly, CD24 immunostaining was effective in diagnosing the presence of dysplasia, correctly discriminating 69% of dysplasia tissues from normal tissues, although no distinction between mild and severe grades of dysplasia was achieved. The results highlight CD24 immunostain intensity as an effective marker of oral dysplasia and OSCC. In conclusion, CD24 immunostain intensity scoring may serve as a helpful technique to assist with the histological recognition of dysplasia in oral biopsies, but not for distinguishing between grades of dysplasia.
authors.affiliation: The University of Queensland, UQ Centre for Clinical Research, Herston, Qld, Australia; The University of Queensland, School of Dentistry, Brisbane, Qld, Australia.
authors.forename: Ahmad A
authors.initials: AA
authors.lastname: Abdulmajeed
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Dalley
authors.forename: Camile S
authors.initials: CS
authors.lastname: Farah
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000080924:Aldehyde Dehydrogenase 1 Family; D015703:Antigens, CD / Q000032:analysis; D014408:Biomarkers, Tumor / Q000032:analysis*; D051927:CD24 Antigen / Q000032:analysis; D002294:Carcinoma, Squamous Cell / Q000737:chemistry*; D002471:Cell Transformation, Neoplastic / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D006801:Humans; D018960:Hyaluronan Receptors / Q000032:analysis; D007527:Isoenzymes / Q000032:analysis; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000737:chemistry*; D014411:Neoplastic Stem Cells / Q000473:pathology*; D009419:Nerve Tissue Proteins / Q000032:analysis; D011230:Precancerous Conditions / Q000737:chemistry* / Q000473:pathology; D017475:Receptors, Nerve Growth Factor / Q000032:analysis; D050697:Retinal Dehydrogenase / Q000032:analysis; D012680:Sensitivity and Specificity; D055815:Young Adult
chemical_list: D015703:Antigens, CD; D014408:Biomarkers, Tumor; D051927:CD24 Antigen; C497889:CD24 protein, human; C497483:CD44 protein, human; D018960:Hyaluronan Receptors; D007527:Isoenzymes; C484065:NGFR protein, human; D009419:Nerve Tissue Proteins; D017475:Receptors, Nerve Growth Factor; D000080924:Aldehyde Dehydrogenase 1 Family; C510223:ALDH1A1 protein, human; D050697:Retinal Dehydrogenase
keywords: ALDH1; CD24; CD271; CD44; oral cancer; oral epithelial dysplasia