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©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
Immunohistochemical expression of matrix metalloproteinase-9 and 13 in oral squamous cell carcinoma and their role in predicting lymph node metastasis
Bhari Sharanesha Manjunatha, Keshav T Handge, Vandana Sandeep Shah, Yasser Eid Al-Thobaiti, Deepak Gowda Sadashivappa Pateel
Bhari Sharanesha Manjunatha, Department of Basic Oral Medicine and Allied Dental Sciences, Taif University, At`Taif 26571, Makkah, Saudi Arabia
Keshav T Handge, Department of Oral and Maxillofacial Pathology, Dr. Vasantrao Pawar Medical College, Hospital and Research Centre, Nashik 423101, Maharashtra, India
Vandana Sandeep Shah, Department of Oral Pathology and Microbiology, KM Shah Dental College and Hospital, Sumandeep Vidyapeeth, Vadodara 391760, Gujarat, India
Yasser Eid Al-Thobaiti, Department of Oral and Maxillofacial Surgery and Diagnostic Sciences, Faculty of Dentistry, Taif University, Al-Haweiah 26571 Makkah, Saudi Arabia
Deepak Gowda Sadashivappa Pateel, Department of Oral Pathology and Microbiology, Faculty of Dentistry, MAHSA University, Selangor 42610, Malaysia
Author contributions: Manjunatha BS, Handge KT, and Shah VS were responsible for research concept, design, and writing the article; Handge KT, Shah VS, and Pateel DGS were responsible for collection and/or assembly of the data; Manjunatha BS, Handge KT, and Al-Thobaiti YE were responsible for data analysis and interpretation; Shah VS and Al-Thobaiti YE were responsible for critical revision of the article; Manjunatha BS, Handge KT, Shah VS, Al-Thobaiti YE, and Pateel DGS were responsible for final approval of the article; all of the authors read and approved the final version of the manuscript to be published.
Institutional review board statement: Local Institutional Ethics Committee approval was obtained under the reference SVIEC/ON/DENT/BN-PG12//D12102.
Informed consent statement: The study did not use any individual’s personal data. All the cases were retrieved from the archives of Department of Oral Pathology and Microbiology, KM Shah Dental College and Hospital, Vadodara, India.
Conflict-of-interest statement: All the authors declare that there is no conflict of interest to disclose.
Data sharing statement: Additional data related to the staining are available with Dr Vandana Shah. However, the information of patients is not available as the cases were retrieved from archives and all patients provided written consent during the diagnosis and treatment sessions at the initial stages when they arrived at the centre.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
https://creativecommons.org/Licenses/by-nc/4.0/ Corresponding author: Bhari Sharanesha Manjunatha, MDS, Associate Professor, Department of Basic Oral Medicine and Allied Dental Sciences, Taif University, At`Taif 26571, Makkah, Saudi Arabia.
drmanju26@hotmail.com
Received: March 19, 2024
Revised: September 23, 2024
Accepted: October 20, 2024
Published online: June 20, 2025
Processing time: 252 Days and 18.7 Hours
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.
Core Tip: The most prevalent type head and neck cancer is oral cavity squamous cell carcinoma (OCSCC). The major cause of the poor prognosis is extensive local invasion that spreads to the lymph nodes. Degradation of the matrix and spread of cancer cells are major characteristics of malignant tumors. Hence, in the present study, matrix metalloproteinase (MMP)-9 and 13 expression was investigated to understand and interpret the invasion and metastasis in OSCC. Most of the cases showed various degrees of staining intensity for MMP-9 and MMP-13. MMP-9 and MMP-13 staining intensity had no significant correlation with tumor size, though a significant relationship (P = 0.000) was observed with metastasis.
