Cytokeratin 8, a Potential Marker for Early Oral Cancer Detection

Objective: Oral cancer is the 6th most common cancer worldwide. Early detection is important in reducing the associated incidence, morbidity, and potential mortality. The intermediate filament cytokeratins 8/18 have recently emerged as potential cellular markers for premalignant changes in oral epithelial cells and increased risk of cancer development. These markers are especially useful because of their abundance, stability, and high antigenicity. Cytokeratin 8 (CK-8) expression is closely related to differentiation abnormalities of epithelial cells and shows a positive correlation with the development of head and neck squamous cell carcinoma.

Methods: Participants were selected from a larger study that examined tissue autofluorescence vs. white light detection of clinically suspicious lesions and oral cancer sites. Healthy volunteers without history of head and neck cancer served as the normal controls. A whole-mouth collection procedure was used to collect buccal cells. Participants were instructed to brush vigorously on the inside of both cheeks and lips with a saline-laden toothbrush for 30-seconds. In addition, they also swished with 10-ml of saline for 60-seconds before expectorating into a collection tube. Samples were spun down to a cell button, embedded into paraffin blocks, sectioned and immunostained with antibodies to CK-8 and CK-AE1/AE3. CK-8 positive samples were categorized based on staining intensity (graded on a 0-3+ scale) and the percentage of cells stained (coding system 1=<10%, 2=<25%, 3=25-50%, 4=50-75%, 5=>75%).

Results: Thirteen subjects (8 with abnormal oral lesions and/or cancer and 5 healthy controls) were tested. The percentage of cells staining positive for CK-8 was significantly higher in the abnormal group (X²=13.0, p-value=.011).

Conclusions: CK-8 expression may serve as a potential biomarker for abnormal differentiation of oral epithelial cells and predict an increased oral cancer risk, based on a simple swish-and-spit buccal cell collection method.