Immunohistochemical evaluation of MMP-2, MMP-9 and CD31/microvascular density in squamous cell carcinomas of the floor of the mouth

Abstract

The aim of this study was to evaluate the immunoexpression of MMP-2, MMP-9 and CD31/microvascular density in squamous cell carcinomas of the floor of the mouth and to correlate the results with demographic, survival, clinical (TNM staging) and histopathological variables (tumor grade, perineural invasion, embolization and bone invasion). Data from medical records and diagnoses of 41 patients were reviewed. Histological sections were subjected to immunostaining using primary antibodies for human MMP-2, MMP-9 and CD31 and streptavidin-biotin-immunoperoxidase system. Histomorphometric analyses quantified positivity for MMPs (20 fields per slide, 100 points grade, ×200) and for CD31 (microvessels <50 µm in the area of the highest vascularization, 5 fields per slide, 100 points grade, ×400). Statistical design was composed by non-parametric Mann-Whitney U test (investigating the association between numerical variables and immunostainings), chi-square frequency test (in contingency tables), Fisher's exact test (when at least one expected frequency was less than 5 in 2×2 tables), Kaplan-Meier method (estimated probabilities of overall survival) and Iogrank test (comparison of survival curves), all with a significance level of 5%. There was a statistically significant correlation between immunostaining for MMP-2 and lymph node metastasis. Factors associated negatively with survival were N stage, histopathological grade, perineural invasion and immunostaining for MMP-9. There was no significant association between immunoexpression of CD31 and the other variables. The intensity of immunostaining for MMP-2 can be indicative of metastasis in lymph nodes and for MMP-9 of a lower probability of survival.

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

“…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 ).…”

“…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.…”

Immunohistochemical analysis of neutrophils, interleukin‐17, matrix metalloproteinase‐9, and neoformed vessels in oral squamous cell carcinoma

“…The inflammatory markers TAN, MMP‐9, and IL‐17 have been individually proposed as prognostic biomarkers in oral squamous cell carcinoma (OSCC) . Garley et al and Li et al observed that the supernatants and blood serum of patients with oral cancer exhibit higher concentrations of IL‐17 than those of healthy subjects, and this difference is associated with tumor growth and metastasis .…”

“…Garley et al and Li et al observed that the supernatants and blood serum of patients with oral cancer exhibit higher concentrations of IL‐17 than those of healthy subjects, and this difference is associated with tumor growth and metastasis . Most of the clinical studies on TAN and MMP‐9 demonstrate that they are associated with poor clinical outcomes, including decreased survival . Similarly, neoangiogenesis shows a positive relationship with poorer prognosis in OSCC …”

“…Nevertheless, no study has yet evaluated this set of markers in OSCC samples. In this way, the characterization of co‐expression of these markers (TAN, MMP‐9, IL‐17, and angiogenesis) in OSCC is relevant, as it seems to contribute to events such as extracellular matrix degradation and angiogenesis, which lead to local invasion, progression, spreading of neoplastic cells, and consequently poor clinical outcomes …”