Immunoexpression of matrix metalloproteinase‐2 and matrix metalloproteinase‐9 in the metastasis of squamous cell carcinoma of the human tongue

Abstract

Background: Squamous cell carcinoma of the tongue has frequent lymph node metastases and poor prognosis. Matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) are reported to degrade basement membrane, facilitating invasion and metastasis. This study determined the expression of MMP-2 ⁄ MMP-9 in primary tongue cancer with or without cervical metastases and analysed the significance of such expression in relation to the presence or absence of metastases. Methods: Expressions of MMP-2 ⁄ MMP-9 were detected by immunohistochemistry in 10 specimens of normal oral mucosa, 20 lymph node-negative tongue cancers, 41 lymph node-positive tongue cancers and their metastasized tumours in cervical lymph nodes. Results: MMP-2 ⁄ MMP-9 expression was seldom found in normal epithelium. In lymph node-negative tongue cancer, 45% and 40% of these primary tumours were positively stained for MMP-2 ⁄ MMP-9, respectively. Importantly, in lymph node-positive tongue cancer, 71% and 79% of these primary tumours were positive for MMP-2 ⁄ MMP-9, respectively. Overexpression of MMP-2 ⁄ MMP-9 was present in the metastatic lymph nodes. Conclusions: Our results imply that MMP-2 and ⁄ or MMP-9 play an important role in invasion and metastasis in tongue cancer, and that analysis of MMP expression and ⁄ or activity in primary tumours may have a predictive value for the actual or potential presence of cervical metastases.

Elevated Matrix Metalloproteinase-9 Expression Correlates With Advanced Stages of Oral Cancer and Is Linked to Poor Clinical Outcomes

“…Based on these results, elevated MMP-9 expression is a useful predictor of metastatic potential and indicates poor prognosis in patients with oral cancer. 20,21 The exact mechanism of how MMP-9 overexpression affects LN metastasis, T stage, and OS in patients with oral cancer remains incompletely understood. print & web 4C=FPO FIGURE 11.…”

“…Then, 9 clinical studies, containing a total of 419 patients with oral cancer, were included in the metaanalysis, and the sample size of the 9 studies ranged from 27 to 74 patients. [20][21][22][23][29][30][31][32][33] The 9 included studies were stratified by clinicopathologic features 20-23,29,31-33 and prognosis. 20,22,23,30,33 Of the 9 studies, 2 were performed in Caucasians (Brazil 23 and Spain 22 ) and the remaining 7 studies were performed in Asians (China 20,21,29,30 and Korea 3133 ).…”

“…Previous studies have associated MMP-9 overexpression with oral cancer progression and poor prognosis in patients with OSCC. 20,21 However, other studies have reported contradictory results. 22,23 In light of the conflicting results, the authors performed a metaanalysis of high-quality cohort studies to investigate the correlation between MMP-9 expression, tumor stage, and prognosis in oral cancer to identify potential novel therapeutic approaches for oral cancer treatment.…”

Matrix‐Metalloproteinases in Head and Neck Carcinoma–Cancer Genome Atlas Analysis and Fluorescence Imaging in Mice

“…6,7 In carcinoma of the tongue, increased MMP2/9 expression has been shown to correlate with an increased incidence of lymph node metastases. 8 …”

An Updated Patent Therapeutic Agents Targeting MMPs

“…The FN2 domains endow MMP-2 & -9 with specific degrading abilities on various constituents of the ECM, such as type IV collagen, which is the major component of vascular membranes, type V collagen, all types of denatured collagens (gelatins), and elastin, facilitating tumor intervention (e.g. invasion, metastasis and angiogenesis) [33]. Accordingly, many researchers focused on designing specific MMPIs with enhanced gelatinase selectivity through interacting with both the active sites as well as exosites like the collagen-binding FN2 domains of the enzyme [34,35].…”