Comparative analysis of the immunohistochemical expression of collagen IV, MMP-9, and TIMP-2 in odontogenic cysts and tumors

Abstract

Objective. The aim of this study was to evaluate the immunohistochemical expression of collagen IV, matrix metalloproteinase (MMP) 9 and tissue inhibitor of MMP (TIMP) 2 in dentigerous cysts (DCs), radicular cysts (RCs), keratocystic odontogenic tumors (KOTs), and ameloblastomas. Study design. Twenty cases of DCs, 20 RCs, 20 KOTs, and 20 ameloblastomas were selected and analyzed by immunohistochemistry. Results. Most DCs and RCs showed continuous and Ͼ50% staining for collagen IV in the basement membrane of the epithelium, whereas predominantly discontinuous thin and Յ50% staining was observed in KOTs and ameloblastomas, with a significant difference in staining percentage (P Ͻ .001). MMP-9 was diffusely distributed and localized in both epithelial and mesenchymal cells of all of the lesions analyzed. The staining percentage was higher in the epithelium (P ϭ .058) and mesenchyme (P ϭ .005) of KOTs and ameloblastomas. Moreover, the distribution pattern, location, and percentage of expression of TIMP-2 were similar in the lesions studied, except for ameloblastoma, with a significant difference in staining percentage (P Ͻ .001).Conclusion. These results demonstrate that the interaction between collagen IV, MMP-9, and TIMP-2 is an important factor for the establishment of differences in the biologic behavior of the odontogenic cysts and tumors studied. Factors related to the epithelial and mesenchymal components participate in the regulation of the growth of odontogenic cystic lesions and tumors. 1 The altered expression of specific proteins of the extracellular matrix (ECM), associated with the exuberant presence of matrix metalloproteinases (MMPs) and the absence of expression of metalloproteinase inhibitors (TIMPs), may influence the behavior of these lesions. In the case of tumors, this situation contributes to the growth and higher aggressiveness of the tumor. 2 The odontogenic keratocyst, recently reclassified as keratocystic odontogenic tumor (KOT), 3 is known for its aggressive nature and high rate of recurrence, especially compared with other odontogenic cysts. 4 Ameloblastoma is a locally aggressive benign epithelial odontogenic tumor with a marked invasion potential that results in multiple recurrences after enucleation and curettage. 5 In contrast, dentigerous (DC) and radicular (RC) cysts show an indolent behavior and rarely recur after surgical removal. KOT presents a cystic structure similar to that of DC and RC, but its invasive and destructive growth is similar to that of ameloblastoma. 6 KOT, ameloblastoma, DC, and RC show distinct evolutions and biologic behaviors. In view of this fact, a growing number of studies have tried to identify

Matrix Metalloproteinase-9 (MMP-9) Expression in Different Subtypes of Ameloblastoma

“…This is in accordance with the result of Henriques et al [22] that found 95 % of ameloblastoma having positive MMP-9 immunoreactions. Most of our specimens show moderate to strong expression intensity.…”

“…Study has shown that MMP-9 is produced by osteoclast in the human bone tissues and suggest that it can degrade bone collagens in concert with MMP-1 and cysteine proteinases in the subosteoclastic microenvironment [16]. Several studies have been conducted to analyze the MMP-9 expression in ameloblastoma [8,[12][13][14][20][21][22]. MMP-9 expression in ameloblastoma is higher than in other odontogenic cysts and keratocyst odontogenic tumor (KOT).…”

Immunohistochemical Analysis of Matrix Metalloproteinases-1,-9 and Tenascin in Odontogenic Lesions

“…The developmental mechanisms of these odontogenic lesions may be related to MMP expression (28). Increased expression of MMP-9 in KOTs compared to other odontogenic cysts has been demonstrated by previous studies (28)(29)(30). Our results showed significantly higherMMP-l and -9 expression in KOTs compared to RCs and DCs, while there was no significant difference in MMP -1 and -9 expression between KOTs andABLs.…”

Odontogenic epithelial proliferation is correlated with COX-2 expression in dentigerous cyst and ameloblastoma

“…Therefore, it is necessary to further elucidate other effects of COX-2 in the epithelium and connective tissue of odontogenic lesions and to compare dentigerous cyst with ameloblastoma. Previous studies have shown that each of ameloblastoma and dentigerous cyst presents a distinct evolution and biological behavior, and in addition to their clinical and behavioral differences (57), they reflect diversities in various features such as gene expression (58), pattern of expression of cytokines (3), interaction of different proteins, and collagen components (57).…”