ABSTRACT
INTRODUCTION: The aim of the study was to investigate the mRNA expression and protein levels of matrix metalloproteinases (MMP) 2 (MMP-2), 9 (MMP-9), 7 (MMP-7) and their tissue inhibitor TIMP-2 in patients with laryngeal squamous cell carcinoma and control subjects and additionally to evaluate a possible correlation with clinicopathological features. MATERIAL AND METHODS: The expression levels of MMP-2, MMP-9, MMP-7, and TIMP-2 mRNA were detected by the real-time quantitative real time polymerase chain reaction method in 96 cases of laryngeal carcinoma vs. non-tumor tissue. The blood serum levels of MMP-2, MMP-9, MMP-7, and TIMP-2 in patients with laryngeal cancer and 100 healthy subjects were measured using the enzyme-linked immunosorbent assay (ELISA) method. RESULTS: The present study demonstrated that MMP-2, MMP-7, MMP-9 and TIMP-2 mRNA expression levels in carcinoma tissue vs. non-tumor tissue and protein levels in the preoperative serum vs. those obtained in healthy controls were statistically significantly higher than in the healthy controls (p = 0.001). The only significant correlation between mRNA or concentration of measured MMPs and TIMP and the clinicopathological features was found for TIMP-2 protein and for patients with lymph node metastasis. Serum levels of TIMP-2 were higher in cases with lymph node metastasis than in those without lymph node metastasis (p < 0.05). CONCLUSIONS: The results may suggest that MMPs and TIMP-2 are associated with laryngeal tumorigenesis, but we did not find any distinct correlation between the clinicopathological features of laryngeal squamous cell carcinoma patients and expression levels of MMPs and TIMP. The results suggest that the measurement of serum MMP-2, MMP-7, MMP-9 and TIMP-2 concentration might be helpful to diagnose laryngeal squamous cell carcinoma.
ABSTRACT
The most common head and neck cancers are neoplasms that occur in the oral cavity and the throat. They are characterized by the high growth rate and clinical malignancy. The research on a significant role in the tumorigenesis of the matrix metalloproteinases MMP-2, MMP-8, MMP-9 and their tissue inhibitors is becoming more and more popular nowadays. MMPs are a group of proteolytic enzymes responsible for the stroma extracellular matrix (ECM) degradation, which enables the tumor growth, cell migration, and tumor invasion. The numerous studies reveal a significant growing trend in the level of the studied metalloproteinases expression and their inhibitors in the oral cavity and throat cancers in relation to healthy tissues. Moreover, it was proved that an increased gene MMP-2 expression in the tumor tissue correlates with the clinical staging, the histopathological grading, presence of metastases, cancer relapse, and the patient's survival time. In available articles there is evidence of increased gene MMP-2 expression as a potential marker of the tumor invasiveness and the worse prognosis in patients with the oral cavity and throat cancers. The relationships of the gene MMP-9 expression with the clinical and pathological features as well as with the survival time are inconclusive. A similar relationship is found in case of TIMPs, however this issue has not been commonly raised in the scientific literature.
