Abstract

BackgroundHead 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.AimThe 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.MethodsUsing 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.ResultsDNA-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.ConclusionEBV and DNA Topo II-αLI expression are possible indicators in oral carcinogenesis and may be valuable diagnostic and prognostic indices in oral carcinoma.

Highlights

  • 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

  • Significant differences were observed between oral epithelial dysplasias (OEDs) and normal squamous epithelium (NSE) (P < 0.001) and SCCs and controls (P < 0.001), significant differences could be observed between SCCs and OEDs

  • Heterogenous reactivity for Epstein Barr virus (EBV) was observed through the series of dysplasia and squamous cell carcinoma

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Summary

Introduction

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 histologic features are predominantly caused by alteration of cell kinetics in the proliferative pool of the epithelium, expressed as increased growth fraction and cell division rate. This alteration determines the transformation of normal oral epithelium into a malignant tumor [3]. The steps of the transformation from normal epithelium to carcinoma are low grade and high-grade oral intraepithelial neoplasias (OINs) These dysplastic alterations are considered to be the precursory steps of the invasive squamous cell carcinoma [4]. Lind reported that the grading of dysplasia was not proportional to the risk of independent transformation [7]

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