Assessment Profile of Biomarker Indexes with FHIT Gene Methylation in Oral Epithelium Tissues among Smokers and Non-smokers in Duhok Province, Iraq

Author(s): Chanar Mousa Sulaiman* and Intisar Salim Pity

Background and objectives: Different pathological and molecular changes can occur in oral epithelium after exposure to cigarette smoking. Management of these changes which may predispose to dysplasia and subsequently invasive cancer depends on the ability to predict malignant transformation like assessment of proliferative index and tumor related genomic markers. Fragile Histidine Triad (FHIT) gene is a tumor suppressor gene that is frequently inactivated by methylation, and this inactivation has been linked to cancer development in many tissues. The present study is aimed to investigate ki67-labeling index, p16 immunoexpression, and the methylation status of the FHIT gene in oral epithelium among smokers. Materials and methods: Tissue samples from 150 oral epithelial were taken from smokers and nonsmokers with different epithelial pathologies. The samples were processed, categorized histologically and studied immunohistochemically for ki67 and p16 expression using the automated immunostainer technique. The methylation status of the FHIT was analyzed by methylation-specific PCR using primer specific for both methylated and unmethylated DNA. Results: Among smokers, both oral squamous cell carcinoma and non-neoplastic oral epithelium (particularly hyperplasia) showed a significant high ki67 expression, while p16 was overexpressed in hyperplastic and inflammatory oral epithelium with a trend toward low grade squamous carcinoma. FHIT methylation was detected among smokers in both non neoplastic oral epithelium and squamous cell carcinoma. Conclusion: Smoking implies a great deal on the degree of ki67 labeling index in both squamous carcinoma and non-neoplastic oral epithelium, while smoking causes p16 overexpression in non-neoplastic epithelium and variable among squamous carcinoma (SSC). Smoking also induced FHIT methylation in neoplastic and non-neoplastic oral epithelium (NNOE).


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