Oral dysplasia and squamous cell carcinoma: Correlation between increased expression of CD21, Epstein-Barr virus and CK19

Objectives: Epstein-Barr virus is an orally transmitted human gammaherpesvirus that infects B lymphocytes and epithelial cells. Although most primary infections are asymptomatic, long term carriage of the virus can be associated with either lymphoid or epithelial malignancies. The association of EBV with oral squamous cell carcinomas is sporadic and it is uncertain if the virus is involved in initiation of the tumor or, possibly, in its progression. Complement receptor type 2, CR2 or CD21, is a receptor for the major attachment protein of EBV, which significantly enhances epithelial cell infection, but its expression on normal tissues is restricted to tonsil and adenoid epithelium. As cells become dysplastic they are reported to express higher levels of CK19. We sought to evaluate whether CD21 and CK19 expression change as oral epithelial cells outside Waldeyer's ring become dysplastic. Materials and methods: Epithelial cells were isolated by laser capture microdissection and levels of CD21, CK19 and EBV RNA were measured by quantitative reverse transcriptase PCR. Results: We report that expression of CD21 increases in frequency and intensity as oral epithelial cells become more dysplastic and that expression correlates with an increase in infection by EBV. Tumors or dysplastic lesions that carry EBV also generally express higher levels of CK19 than those that do not. Conclusion: The findings suggest that dysplasia may make cells more susceptible to infection by EBV and that infection by the virus may alter the phenotype of the infected cell in a manner which could affect prognosis. (C) 2012 Elsevier Ltd. All rights reserved.