Oral cancer is one of the 10 most common types of cancer worldwide accounting for nearly 3% of all cancer cases. It is more common in men than women and two-thirds of oral cancers occur in developing countries. The primary standard of care is surgical resection with or without postoperative adjuvant therapy. Clinical and biological factors such as stage, etiology, site of the disease, comorbidities, and patient performance status determine prognosis. Oral cavity subsites include lips, gingiva, floor of mouth, alveolar mucosa, vestibule, oral tongue, retromolar trigone, and hard palate. The anatomical location of cancer occurrence within the oral cavity may also serve as an indicator of metastatic potential. There is a critical need to develop molecular diagnostic/prognostic biomarkers for better understanding the subsite influences on oral cancer behavior.

Matrix metalloproteinases (MMPs) are enzymes involved in common physiological processes, such as angiogenesis, proliferation, differentiation and apoptosis. Patient stromal cells have been shown to regulate MMP expression. MMP degradation of extracellular matrix can release growth factors capable of modulating angiogenesis and tumor cell behavior. Previous studies demonstrated that MMP2/9 are important contributory factors for various cancers.

Our study evaluated the expression of MMP-9 and MMP-2 in 121 histopathologically confirmed OSCC patients from different anatomical subsites: tongue, floor of mouth, buccal mucosa, and alveolar ridge. We also analyzed MMP site-specific differences between OPMDs and carcinomas in these same subsite cohorts. Standard immunohistochemistry was performed on FFPE sections followed by evaluation of MMP-2 and MMP-9 expression using the H-scoring method. Two pathologists independently scored each section. The blinded, independent scores were averaged and decoded for analysis. All statistical analyses were performed using GraphPad Prism.

Profiling of MMP-2 and MMP-9 in different anatomical subsites within the oral cavity supports our ongoing investigation of oral subsite biology and may led to their use as prognostic biomarkers. Understanding MMP expression in premalignant and malignant pathologies, along with their site-specific patterns may provide insight into potential treatment targets in OSCC.