Immunohistochemical expression of matrix metalloproteinase-9 and 13 in oral squamous cell carcinoma and their role in predicting lymph node metastasis

Abstract

Background: One of the main characteristics of oral squamous cell carcinoma (OSCC) is that it metastasizes to cervical lymph nodes frequently with a high degree of local invasiveness. A primary feature of malignant tumors is their penetration of neighboring tissues, such as lymphatic and blood arteries, due to the tumor cells' capacity to break down the extracellular matrix (ECM). Matrix metalloproteinases (MMPs) constitute a family of proteolytic enzymes that facilitate tissue remodeling and the degradation of the ECM. MMP-9 and MMP-13 belong to the group of extracellular matrix degrading enzymes and their expression has been studied in OSCC because of their specific functions. MMP-13, a collagenase family member, is thought to play an essential role in the MMP activation cascade by breaking down the fibrillar collagens, whereas MMP-9 is thought to accelerate the growth of tumors. Elevated MMP-13 expression has been associated with tumor behavior and patient prognosis in a number of malignant cases.

Aim: To assess the immunohistochemical expression of MMP-9 and MMP-13 in OSCC.

Methods: A total of 40 cases with histologically confirmed OSCC by incisional biopsy were included in this cross-sectional retrospective study. The protocols for both MMP-9 and MMP-13 immunohistochemical staining were performed according to the manufacturer's recommendations along with the normal gingival epithelium as a positive control. All the observations were recorded and Pearson's χ² test with Fisher exact test was used for statistical analysis.

Results: Our study showed no significant correlation between MMP-9 and MMP-13 staining intensity and tumor size. The majority of the patients were in advanced TNM stages (III and IV), and showed intense expression of MMP-9 and MMP-13.

Conclusion: The present study suggests that both MMP-9 and MMP-13 play an important and independent role in OSCC progression and invasiveness. Intense expression of MMP-9 and MMP-13, irrespective of histological grade of OSCC, correlates well with TNM stage. Consequently, it is evident that MMP-9 and MMP-13 are important for the invasiveness and progression of tumors. The findings may facilitate the development of new approaches for evaluating lymph node metastases and interventional therapy techniques, hence enhancing the prognosis of patients diagnosed with OSCC.

Keywords: Immunohistochemistry; Invasion; Lymph node metastasis; Matrix metalloproteinases; Oral squamous cell carcinoma; TNM stage; Tumor staging.