Study of Hypoxia-inducible factor-2α expression in the malignant transformation of Oral submucous fibrosis

Abstract

Context:

Hypoxia-inducible factor (HIF)-2α is overexpressed in primary and metastatic human cancers, whose expression is correlated with tumor angiogenesis and patient mortality. HIF plays a role in the progression of fibrosis in oral submucous fibrosis (OSF).

Aim and Objective:

The aim is to study and compare the expression of HIF-2α in OSF (a), oral squamous cell carcinoma (OSCC) with areca nut usage (b), OSCC without areca nut usage (c) and normal mucosa (d) by immunohistochemistry.

Subjects and Methods:

Immunohistochemical detection of HIF-2α was done on 51 samples, which included 11 cases (a), 15 cases (b), 15 cases (c) and the expression was compared with that of (d).

Statistical Analysis

Data were analyzed using the SPSS™ software (ver. 21.0). Chi-square test and kappa analysis were performed to compare the intensity of staining between the groups and for inter-observer agreement, respectively. Value of P ≤ 0.05 was considered statistically significant. The mean labeling index between the groups was studied by the Kruskal–Wallis test.

Results:

All the cases of (d), (a), (b) and (c) showed HIF-2α expression ( P = 0.329). About 13% cases of (c) showed intense expression ( P = 0.406) and 27% of (a) cases showed expression only in the connective tissue ( P = 0.023). The number of positively stained nuclei in both (b and c) cases reduced as the tumor progression was from well to poorly differentiated.

Conclusion:

Areca nut initiates fibrosis and subsequent hypoxia in OSF which triggers HIF-2α expression in the epithelium. HIF-2α could be a surrogate marker for cancer initiation and progression.