The domino effect: Role of hypoxia in malignant transformation of oral submucous fibrosis

Abstract

INTRODUCTION: Oral submucous fibrosis (OSMF) is a precancerous condition predominantly seen in people of Asian descent. About 7-12% OSMF patients develop oral squamous cell carcinoma (OSCC). Morphological features of OSMF especially fibrosis suggests a possibility of the hypoxic environment in diseased tissues. Oral cancer usually develops from hyperplasia through dysplasia to carcinoma. Neovascularization and increased glycolysis, represent adaptations to a hypoxic microenvironment that are correlated with tumor invasion and metastasis. The adaptation of cells to hypoxia appears to be mediated via hypoxia inducible factor-1α (HIF-1α). HIF-1α is said to be associated with malignant transformation of epithelium in other sites. It appears that HIF-1α plays a significant role in both prostate and cervical carcinogenesis at early stages. We hypothesize that progression of OSMF and malignant transformation in the background of fibrosis mediates via HIF-1α either by up- or down-regulation of various such molecules. Therefore, the main objective of this study was to investigate the relationship between the expression of HIF-1α in OSMF, OSCC and OSCC with OSMF. AIM: To investigate the relationship between the expression of HIF-1α in OSMF, OSCC and OSCC with OSMF. MATERIALS AND METHODS: The study group consists of histopathologically diagnosed 20 cases of OSCC, oral submucous fibrosis and OSCC with OSMF each. The immunohistochemistry was carried out on neutral buffered formalin-fixed paraffin-embedded tissue sections by using the monoclonal antibody of HIF-1α. RESULTS: A rise in the expression of HIF-1α from OSMF to OSCC to OSCC with OSMF is observed.