Imbalance between Matrix Metalloproteinases and Tissue Inhibitors of Metalloproteinases Promotes Invasion and Metastasis of Head and Neck Squamous Cell Carcinoma.

BACKGROUND: The balance between collagenolysis and its inhibition is critical during extracellular matrix remodeling in head and neck squamous cell carcinoma (HNSCC). An imbalance between matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) plays a critical role in the development of tumor cell invasion and metastasis. The purpose of the study was to determine MMP-9/TIMP-1 and MMP-2/TIMP-2 ratios in the sera of patients with HNSCC in relation to clinicopathological parameters. METHODS: Serum samples from seventy patients with HNSCC were measured by ELISA, before and 2 days after surgery. Forty healthy volunteers were selected as controls. RESULTS: Preoperative MMP-9/TIMP-1 and MMP-2/TIMP-2 ratios were significantly higher in HNSCC patients than in the control group (p < 0.001 and p = 0.002, respectively). Changes in MMP-9 concentration and MMP9/TIMP-1 ratio after surgery had a negative correlation with lymph node involvement (r = - 0.35, p = 0.021 and r = - 0.37, p = 0.013), while changes in TIMP-1 had a positive one (r = 0.45, p = 0.006). Histological grade was positively correlated with the changes in circulating TIMP-2 level (r = 0.39, p = 0.021). No significant correlation was discovered between MMP-2/TIMP-2 ratio and tumor grade or any clinicopathological variables. CONCLUSIONS: Our results suggest that an imbalance between MMP-9 and TIMP-1 could play an important role in metastatic spread via lymphatic pathways of HNSCC cells. MMP-9/TIMP-1 ratio and, in particular, MMP-9, TIMP-1, TIMP-2, may represent suitable biomarkers for early diagnosis and detection of disease progression and dissemination in HNSCC patients.

Serum Level of Matrix Metalloproteinase-9 in Patients with Head and Neck Squamous Cell Carcinoma.

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is characterized by the upregulation of a large number of matrix metalloproteinases (MMPs). The aim of the study was to investigate the level of MMP-9 in the sera of HNSCC patients and its relationship to clinicopathological features. METHODS: Serum samples from sixty-five patients (56M/9F, 59.11 ± 9.02 years) with HNSCC were quantitatively measured by ELISA assay, before and two days after surgery. Forty healthy volunteers served as controls (29M/ 11F, 56.21 ± 12.13 years). RESULTS: Median serum concentrations of MMP-9 were consistently upregulated in HNSCC patients both preoperatively (1593.0 ng/mL, IQR: 833.0 - 1942.0 ng/mL) and postoperatively (1382.0 ng/mL, IQR: 778.6 - 2062.0 ng/mL) in comparison to healthy controls (291.3 ng/mL, IQR: 223.8 - 330.5 ng/mL) (p < 0.001). Pretreatment levels of MMP-9 were related to the size of primary tumor (p = 0.018) and lymph node involvement (p = 0.045). No statistically significant association was found between serum MMP-9 concentrations and clinical stage or degree of differentiation of the tumor cells. CONCLUSIONS: Serum MMP-9 level could be used as a diagnostic tool for early detection of HNSCC and for determining prognosis. Moreover, our results suggest that MMP-9 might be a good marker in evaluating the size of the primary tumor and lymph node involvement. Further studies are needed to show whether MMP-9 could serve as a marker for recurrence.

Clinical significance of serum melatonin in predicting the severity of oral squamous cell carcinoma.

Melatonin, the primary hormone produced by the pineal gland, is intensely assessed for its anticancer properties. This study aimed to reveal the clinical significance of serum melatonin levels in predicting the severity of oral squamous cell carcinoma (OSCC). For this purpose, 40 male patients with OSCC and 30 healthy subjects were enrolled in this study. The serum levels of melatonin were determined by ELISA. The results revealed that the melatonin concentrations were significantly lower in the patients with OSCC compared with the controls (18.2 vs. 47.6 pg/ml, P<0.001). In addition, the serum melatonin levels had a high predictive accuracy for discriminating patients with OSCC with T-depth of invasion (DOI) II from the healthy controls (89.1%), as well as in discriminating patients with OSCC with nodal metastasis from those without nodal metastasis (83.8%). On the whole, the findings of this study suggest that the serum melatonin concentrations are closely related to the severity of OSCC and may thus be used to assess the different stages of oral cancer objectively and accurately. The present study also supports the conclusion that melatonin may be a potential therapeutic agent for use in the treatment of patients with OSCC.