Immunohistochemical Expression of MMP-9, TIMP-1, and Vimentin and its Correlation With Inflammatory Reaction and Clinical Parameters in Oral Epithelial Dysplasia

Abstract

The aim of this study was to investigate the immunoexpression of matrix metalloproteinase 9 (MMP-9), tissue inhibitor of metalloproteinase 1 (TIMP-1), and vimentin (VIM) and its association with the inflammatory reaction (IR) and clinical parameters in oral epithelial dysplasia (ED). The sample was composed of 66 cases of ED, 27 oral squamous cell carcinoma (OSCC), and 28 nonneoplastic epithelium (NNE). ED was graded according to the binary system as low-risk ED (n = 42) and high-risk epithelial dysplasia (HRED: n = 24). The IR was defined as the median number of inflammatory cells present on the connective tissue in 5 consecutive fields. Tissue sections of paraffin-embedded samples were immunohistochemically stained; MMP-9 and TIMP-1 expression was analyzed separately in the epithelium and the connective tissue; VIM was analyzed in the epithelium. Clinical parameters such as age, sex, lesion site and clinical presentation, alcohol/tobacco use, and malignant transformation of ED were retrospectively obtained from medical records. Nonhomogeneous leukoplakia presented higher odds (3.857; 95% confidence interval: 1.16-12.85) of being graded as HRED than did homogeneous lesions. The IR was higher in OSCC and ED than in NNE, and correlated with the epithelial expression of VIM. HRED and nonhomogeneous leukoplakias presented higher IR than did low-risk ED and homogeneous leukoplakias. Alcohol users had higher IR than nonalcohol users. Smokers had higher epithelial expression of MMP-9 and VIM. High IR in OSCC and HRED, and its positive correlation with VIM expression suggest a contribution of the IR in the progression of OSCC. Moreover, the high expression of MMP-9 and VIM in smokers implies its involvement in tobacco carcinogenesis.

Oral field cancerization: Genetic profiling for a prevention strategy for oral potentially malignant disorders

“…Various protein expressions or markers have been revealed at the tissue level and may be easier to replicate in clinical settings than DNA analysis. These include the expression of Ki-67, 38 kaiso, e-cadherin, 41 stathmin, 42 Oct 4+ , Sox 2+ , 43 GLUT-3, GLUT 4, 44 substance p, NK-1R, 45 podoplanin, 36 matrix metalloproteinase 9 (MMP-9), tissue inhibitor of metalloproteinase 1 (TIMP-1), vimentin (VIM), 46 cornulin, 38 transforming growth factor (TGF-β1) and interleukin 17-A (IL-17A). 47 These markers are essential in detecting oral cancer, especially OSCC.…”

The Multiple Roles of CD147 in the Development and Progression of Oral Squamous Cell Carcinoma: An Overview

“…Results from clinical–epidemiological studies indicate that chronic inflammation of the oral mucosa significantly augments the risk of OSCC onset and its clinical progression [ 103 , 104 , 105 ]. Inflammation occurs in response to most of the agents causing oral lesions [ 27 , 103 , 104 ] and implies that neutrophils, lymphocytes, and monocytes extravasate in the oral tissues: this phenomenon is facilitated by the fact that leukocytes express CD147 [ 26 , 106 , 107 ], which, in turn, binds to endothelial–leukocyte adhesion molecules, such as endothelial selectin ( Table 2 ) [ 51 ].…”

“…As is the case for oral mucositis, the number of tissue-infiltrating inflammatory cells is elevated in low-risk OPMDs as compared to healthy oral mucosa, being further augmented in high-risk OPMDs and OSCCs [ 105 ]. In these pathological settings, leucocytes release cytokines, among which interleukin (IL)-1β, IL-6, IL-8, and tumor necrosis factor (TNF)α are particularly abundant [ 79 , 108 , 109 ].…”

“…While physiological, quickly reversable EMT occurs in tissue repair, persistent and exacerbated EMT takes place during cancerogenesis [ 179 , 180 , 186 , 187 ]. For OSCCs and high-risk OPMDs, the concomitant presence of numerous cytokines capable of activating ZEB, SNAI, and/or TWIST induces a lasting EMT in epithelial cells, whether they are normal or transformed ( Figure 2 ) [ 105 , 188 , 189 ]. As expectable, in either OPMDs or OSCCs, the number of EMT cells correlates with that of infiltrating inflammatory cells [ 105 ].…”

“…For OSCCs and high-risk OPMDs, the concomitant presence of numerous cytokines capable of activating ZEB, SNAI, and/or TWIST induces a lasting EMT in epithelial cells, whether they are normal or transformed ( Figure 2 ) [ 105 , 188 , 189 ]. As expectable, in either OPMDs or OSCCs, the number of EMT cells correlates with that of infiltrating inflammatory cells [ 105 ]. In agreement with the fact that the stimulation of CD147 triggers the same signaling pathways (namely MAPK/ERK and PI3K/AKT) which activate the EMT-promoting transcription factors ( Figure 2 ), in OSCC tissues, the number of cells which have undergone EMT positively correlates with the intensity of CD147 expression ( Table 2 ) [ 54 , 190 ].…”