DO MYOFIBROBLASTS DETERMINE THE BIOLOGICAL BEHAVIOR OF ODONTOGENIC CYSTS AND TUMORS?

Abstract

<h3>Background</h3> Studies have shown increased numbers of myofibroblasts (MFs) in the stroma of odontogenic lesions with locally aggressive biological behavior. Keratinocytes in odontogenic lesions have been shown to release transforming growth factor (TGF)-β1, which activates the transdifferentiation of fibroblasts to MFs. In turn, MFs secrete matrix metalloproteinase (MMP)-2, potentiating active, rather than passive, lesional growth through bone resorption. <h3>Objective</h3> To assess the expression of MFs, TGF-β1, and MMP-2 using immunohistochemistry in odontogenic cysts and tumors and to correlate the findings with the biological behavior of the lesions. <h3>Methods</h3> Formalin-fixed paraffin-embedded tissue samples of locally aggressive (odontogenic keratocysts [OKC], n = 11; ameloblastoma [AM], n = 11) and nonaggressive (radicular cysts [RC], n = 12; dentigerous cysts [DC], n = 10) odontogenic cysts and tumors were stained with antibodies against α-SMA, h-Caldesmon, TGF-β1, and MMP-2. Qualitative and quantitative analyses of positively stained cells were undertaken and compared between the groups. <h3>Results</h3> Analysis of MFs was achieved with the inclusion of anti-h-Caldesmon. The expression of MFs and MMP-2 was significantly higher in the locally aggressive group (OKC and AM) in comparison with the nonaggressive group (RC and DC; <i>P</i> < .0001). Interestingly, this was opposite for the cytokine TGF-β1, in which an increased expression was observed in RC and DC compared with the aggressive group (<i>P</i> < .05). <h3>Conclusion</h3> The high expression of MFs and MMP-2 positive cells in aggressive odontogenic lesions (OKC and AM) suggests that these cells may be responsible for the biological behavior of these lesions.