Expression of cornulin in oral premalignant lesions

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Objective

The aim of this study was to evaluate expression of cornulin in oral mucosa as an adjunct to histopathologic grading of oral epithelial dysplasia (OED).

Study Design

Biomarker expression was assessed in normal oral mucosa, low-grade OED (LD), high-grade OED (HD), and oral squamous cell carcinoma (OSCC) by using immunohistochemistry. Photomicrographs were evaluated with Aperio Imagescope using a positive-pixel-counting algorithm. A histo-score (H-score) was calculated on the basis of staining intensity and the percentage of positive cells (%-staining). Intrarater reliability for H-score and %-staining was determined by calculating interclass correlation coefficients. Mean differences in H-scores and %-percent staining values were each analyzed by using an analysis of variance and Tukey's post hoc procedure.

Results

Cornulin expression progressively diminished with increasing grades of dysplasia and OSCC. Interclass correlation coefficients for H-score and %-staining were each greater than 0.99. Except for OSCC versus HD, all other pairwise comparisons were statistically significant (P < .0001) for H-score and %-staining.

Conclusions

Cornulin expression helped differentiate between low-grade and high-grade oral epithelial dysplasia, making it a potential adjunct for grading oral OEDs and a potential biomarker for risk of lesion progression. Longitudinal studies evaluating risk stratification based on cornulin expression may be warranted.

Section snippets

Patient identification and sampling

This study was deemed exempt from review by the Ohio State University Institutional Review Board (protocol No. 2014 E0457) because it was a retrospective study of archived pathology specimens that were deidentified before analysis. An electronic database review of tissue archives of the Oral Pathology Consultants at the Ohio State University College of Dentistry was performed. Specimens diagnosed between the years 2010 and 2013 as NOM; mild, moderate, or severe epithelial dysplasia; carcinoma

Results

Summarized patient characteristics of age- and gender-matched cohorts are provided in Table I. IHC analysis using antibodies directed against cornulin showed strong cytoplasmic staining of the keratin, the granular layer (if present), and the spinous layer of the surface stratified squamous epithelium, whereas no staining was observed in the basal cell layer. NOM exhibited the most intense staining, and staining intensity decreased with increased grades of OED (LD > HD) and was minimal or

Discussion

We investigated the expression of cornulin in the oral mucosa and its potential utility as an adjunct in the assessment and histopathologic grading of OED. Cornulin expression demonstrated promise as a supplement to routine histopathologic assessment of oral potentially malignant lesions (OPMLs).

Our results showed progressive downregulation of cornulin in OED and OSCC compared with NOM, validating the findings of Xiao et al.27; however, those authors had examined microarray samples, whereas in

Conclusions

Cornulin expression in surface oral epithelium is progressively decreased with increasing grades of OED and OSCC. Cornulin expression was able to differentiate between LD and HD and could, thus, represent a potential biomarker for assessing the risk of progression in OPMLs. Longitudinal studies evaluating risk stratification based on cornulin expression may be warranted.

Acknowledgments

We would like to thank Dr. Mark Lingen of the Department of Pathology, University of Chicago, Chicago, IL, for his intellectual contributions.

Disclosure

This study was funded by The Ohio State University College of Dentistry's Seed Grant Program (project No. 21-100278); and was presented in part as an abstract at the Annual Meeting of American Academy of Oral and Maxillofacial Pathology, Cincinnati, OH, May 2016.

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    Present address: Department of Biomedical Sciences and Comprehensive Care & Department of Oral Pathology, Medicine and Radiology, Indiana University School of Dentistry, Indianapolis, IN, USA.

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