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The significance of Epstein Barr Virus (EBV) & DNA Topoisomerase II alpha (DNA-Topo II alpha) immunoreactivity in normal oral mucosa, Oral Epithelial Dysplasia (OED) and Oral Squamous Cell Carcinoma (OSCC)

Ali A Shamaa1*, Manal M Zyada2, Mathias Wagner3, Sally S Awad4, Mohamed M Osman5 and Ali A Abdel Azeem1

Author affiliations

1 Oral Biology Department, Faculty of Dentistry, Minia University, Minia, Egypt

2 Oral Pathology Department, Faculty of Dentistry, Mansoura University, Mansoura, Egypt

3 General Pathology Department, Saarland University, Saarland, Germany

4 Oral Surgery Department, Faculty of Dentistry, Mansoura University, Mansoura, Egypt

5 Oral Surgery Department, Faculty of Dentistry, Misr International University, Cairo, Egypt

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Citation and License

Diagnostic Pathology 2008, 3:45  doi:10.1186/1746-1596-3-45

Published: 20 November 2008



Head and neck cancer including oral cancer is considered to develop by accumulated genetic alterations and the major pathway is cancerization from lesions such as intraepithelial dysplasia in oral leukoplakia and erythroplakia. The relationship of proliferation markers with the grading of dysplasia is uncertain. The involvement of EBV in oral carcinogenesis is not fully understood.


The present study was designed to investigate the role of EBV and DNA Topoisomerase II∝ (DNA-Topo II∝) during oral carcinogenesis and to examine the prognostic significance of these protein expressions in OSCCs.


Using specific antibodies for EBV and DNA-Topo II∝, we examined protein expressions in archival lesion tissues from 16 patients with oral epithelial dysplasia, 22 oral squamous cell carcinoma and 20 normal oral mucosa by immunohistochemistry. Clinical information was obtained through the computerized retrospective database from the tumor registry.


DNA-Topo II∝ was expressed in all examined specimens. Analysis of Variance ANOVA revealed highly significant difference (P < 0.01) in young aged labial tissues and significant (P ≤ 0.05) in gingival and not significant (P > 0.05) in inferior surface of tongue and in hard palatal tissues. Significant differences were observed between OEDs and NSE (P < 0.001) and SCCs and controls (P < 0.001), also, significant differences could be observed between SCCs and OEDs. DNA-Topo II∝ expression was significantly higher in tumors of low differentiation versus tumors of moderate and high differentiation (P < 0.001), DNA-Topo II∝ expression was correlated with age, tumor size, tumor stage, node metastasis and tumor differentiation, but not with gender and tumor site. None of normal squamous epithelium (NSE) expressed EBV. Heterogenous reactivity for EBV was observed through the series of dysplasia and squamous cell carcinoma. Its expression increased progressively with lymph node metastasis and low tumor differentiation, but no significant association could be observed with other clinicopathological parameters. EBV protein expression was increased with elevated Topo II-∝ LI in OEDs and OSCCs. A tendency to positive correlation between EBV and Topo II∝ expression was observed in OEDs but not in OSCCs.


EBV and DNA Topo II-αLI expression are possible indicators in oral carcinogenesis and may be valuable diagnostic and prognostic indices in oral carcinoma.