Oral Submucous Fibrosis (osmf)

Oral submucous fibrosis (OSMF), first described in early 1950s, is a potentially malignant disease predominantly seen in people of Asian descent. It is a chronic progressive disorder and its clinical presentation depends on the stage of the disease at the time of detection.OSMF is characterized by inflammation and progressive fibrosis of lamina propria and deeper connective tissues, followed by stiffening of an otherwise yielding mucosa resulting in difficulty in opening the mouth.

Worldwide, estimates of OSMF shows a confinement to Southeast Asians, with overall prevalence rate in India to be about 0.2% to 0.5 % and prevalence by gender varying from 0.2-2.3% in male and 1.2-4.57% in female. The morbidity rate is high in OSMF because there is progressive inability to open the mouth which results in difficulty in eating and consequent nutritional deficiencies. Amongst other potentially malignant oral disorders (PMOD), OSMF has one of the highest rates of malignant transformation into oral squamous cell carcinoma (OSCC), at the rate of 7.6%, hence the mortality rate is also high.Research reports state that OSCC originated from OSMF is clinically more invasive and also exhibits higher metastasis and recurrence rate than OSCC not originated from OSMF(5)(6).

The pathogenesis of the disease is believed to be multifactorial. A number of factors trigger the disease process by causing a juxtaepithelial inflammatory reaction in the oral mucosa. Factors include areca nut chewing, ingestion of chilies, genetic and immunologic processes and nutritional deficiencies of iron, zinc and essential vitamins. In addition, a possible autoimmune basis to the disease with demonstration of various auto antibodies and an association with specific human leukocyte antigen (HLA) has been proposed. Of all these areca nut is one of the main etiological factors.

Constant local irritation by pan masala, gutkha or areca nut can thus lead to injury related chronic inflammation, oxidative stress and cytokine production. Local trauma and injury to the oral mucosa is due to the abrasive nature of areca nut. Other deleterious effects of such reactions result in chronic inflammation leading to activation of macrophages and T cells and an increase in the level of cytokines such as interleukin-6 (IL-6), tumor necrosis factor (TNF), interferon alpha (IFN- α) and transforming growth factor beta (TGF- β).

Progranulin (PGRN) also known as granulin-epithelin precursor, is a glycoprotein of 576 amino acids, pleiotropic in nature, and is known to play an important role in the maintenance and regulation of tissue development, embryogenesis, infectious diseases, inflammatory conditions, wound healing, & tumorigenesis. PGRN has been studied extensively in the context of rheumatoid arthritis, is a chronic inflammatory autoimmune disease which is mediated by TNF-α.

Various studies have been done for the estimation of PGRN in several cancers and also few inflammatory diseases. The functions of progranulin are multifaceted; progranulin levels have yet been unexplored in the context of submucous fibrosis as well as oral cancer.

Enzyme linked immunosorbent assay (ELISA) is an established method used for estimating the levels of PGRN directly from the biological specimen (serum and saliva) with very little preparation of the sample. Hence the present study aims to assess the serum and salivary levels of Progranulin in patients of oral submucous fibrosis and compare the same with normal control subjects.