Increased Expression of Cytokeratin 19 in Oral Squamous Cell Dysplasia Is Associated with Susceptibility to Infection with Epstein-Barr Virus (EBV)
Ru Jiang, Xin Gu, Tara Moore-Medlin, Cherie-Ann Nathan, Lindsey Hutt-Fletcher. LSUHSC, Shreveport, LA
Background: EBV, an orally transmitted herpesvirus that targets B cells and epithelial cells, is associated with development of both B cell lymphomas and nasopharyngeal carcinoma. Infection of B cells is initiated by binding of virus to the complement receptor CD21. Infection of CD21-negative epithelial cells is inefficient but efficient infection can be achieved if expression of CD21 is engineered. Whether EBV infection plays an etiologic role in oral squamous cell dysplasia (OSD) and malignant transformation is unclear. The aim of this study was to evaluate CD21 expression in OSD and its association with the epithelial stem cell marker CK19 that is elevated in oral squamous cell carcinoma (OSCC).
Design: Formalin-fixed paraffin-embedded tissue blocks were retrieved and separated by pathologic grade as follows: normal margin epithelium of OSD (n=6), low-grade OSD (LSD, n=8) and high-grade OSD (HSD, n=21). Squamous cells were isolated by laser capture microdissection. Isolated mRNA was amplified using qRT-PCR with target primers specific for the CD21 exons coding for the EBV binding site, for CK19 and for EBV small RNA, EBER1. CK19 expression was also examined by immunohistochemistry (IHC). IHC for CD21 has not proven reliable.
Results: Normal margins of OSD were negative for both CD21 and EBV. CD21 expression was found in 12.5% (1/8) LSD samples and 57.1% (12/21) HSD samples. Transcript levels were 0.35 and 2.97 fold higher, respectively, than in the Akata B cell line (set arbitrarily at 1). EBV could also be detected in some samples of OSD. CK19 was detected in normal epithelial margin at low transcript levels. Transcript levels were increased significantly in EBV positive OSD (P<0.025), but not in EBV negative OSD (p>0.05). Increased CK19 was confirmed at the protein level by IHC.
Conclusions: CD21 mRNA is expressed in dysplastic oral epithelium, and is up-regulated as the grade of dysplasia increases. Expression of CK19 is increased in premalignant dysplasia and the increase is correlated with the presence of EBV. CK19 is a stem cell marker which is elevated in OSCC and is associated with increased epithelial mesenchymal transition. Increased susceptibility of epithelial cells to EBV may be involved in the process of oral squamous cell differentiation and precipitate malignant transformation.
Category: Head & Neck
Wednesday, March 21, 2012 9:30 AM
Poster Session V # 177, Wednesday Morning