Study of Hypoxia Inducible Factor (HIF)– 2 Alpha Expression in the Malignant Transformation of Oral Submucous Fibrosis

Joseph, I (2016) Study of Hypoxia Inducible Factor (HIF)– 2 Alpha Expression in the Malignant Transformation of Oral Submucous Fibrosis. Masters thesis, Ragas Dental College and Hospital, Chennai.


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BACKGROUND: HIF – 2 alpha is over-expressed in primary and metastatic human cancers, and the level of expression is correlated with tumor angiogenesis and patient mortality. Molecules upregulated by hypoxia (HIF alpha) play a role in progression of fibrosis in OSMF. To ascertain the role of HIF – 2 alpha as a surrogate biomarker in the malignant transformation of Oral Submucous Fibrosis, a potential malignant disorder/ premalignant condition. AIM AND OBJECTIVES: To study and compare the expression of HIF – 2 alpha in oral submucous fibrosis (OSMF), Oral Squamous cell carcinoma (OSCC) with history of areca nut usage, OSCC without areca nut usage and normal mucosa by immunohistochemistry. MATERIAL AND METHODS: Immunohistochemical detection of HIF – 2 alpha was done using monoclonal antibody of clone ep-190b and Poly Excel HRP/DAB chromogen detection system on 51 samples, which included oral submucous fibrosis (OSMF - 11 cases), oral squamous cell carcinoma with history of areca nut usage (OSCC - 15 cases), oral squamous cell carcinoma without areca nut usage (OSCC - 15 cases) and the expression was compared with that of normal mucosa (10 cases). The positive control used for HIF-2 alpha was pre-eclamptic placenta. RESULTS: All the cases of normal mucosa, OSMF, OSCC with areca nut habit and OSCC without areca nut habit showed HIF-2α expression. Connective tissue staining alone was seen in 27% of OSMF cases and there was a significant difference in the proportion of cases, which had expression in the suprabasal, basal and suprabasal layers of epithelium between the groups. An intense expression of HIF-2α was seen in 13% cases of OSCC associated with areca nut habit. Mild and moderate expression was seen in most cases of OSMF, OSCC and normal control groups. The pattern of HIF-2α staining in most of the cases of normal mucosa, OSMF and OSCC was cytoplasmic and nuclear. All the cases of OSCC with areca nut habit had their staining either cytoplasmic or nuclear and cytoplasmic. As the tumor progressed from well to poor differentiation, there was a reduction in the number of positive stained nuclei and also there was no correlation with the intensity of the expression of HIF-2α, which increased as the tumor became poorly differentiated. CONCLUSION: Areca nut habit induces hypoxia in OSMF which triggers the expression of HIF-2α in the epithelium. HIF-2α could be a marker for cancer initiation and progression.

Item Type: Thesis (Masters)
Uncontrolled Keywords: HIF-2α, angiogenesis, hypoxia, oral potentially malignant disorder.
Subjects: DENTAL > Oral Pathology and Microbiology
Depositing User: Subramani R
Date Deposited: 24 Sep 2021 16:45
Last Modified: 24 Sep 2021 16:45

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