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

BACKGROUND

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.

OBJECTIVE

To investigate the relationship between the expression of HIF-1α in OSMF, OSCC and OSCC with OSMF.

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.