title: Interplay Between MMP-9 and TIMP-2 Regulates Ameloblastoma Behavior and Tooth Morphogenesis.
abstract: Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) have been implicated in the local invasiveness of ameloblastoma. This study aims to assess the role of MMP-9 and TIMP-2 in regulating tumor progression in ameloblastomas, taking tooth germs as control. Formalin-fixed, paraffin-embedded tissue sections of 4 tooth germs and 32 ameloblastomas were immunohistochemically examined using antibodies against MMP-9 and TIMP-2. Strong MMP-9 positivity was seen in the epithelial component in both controls and solid multicystic ameloblastoma. Statistically significant difference was observed in the mean stromal MMP-9 immunoscores between follicular, acanthomatous, and granular ameloblastoma when compared with the tooth germ (P=0.004). TIMP-2 expression in the epithelial and mesenchymal components of solid multicystic ameloblastoma and tooth germ was weak as compared with MMP-9 expression. Highest mean epithelial TIMP-2 immunoscore was observed in follicular ameloblastoma and the difference was statistically significant between follicular and granular ameloblastoma (P=0.05). The comparison of mean stromal TIMP-2 immunoscores showed statistically significant difference between follicular subtype and tooth germ (P=0.048), with tooth germ showing least expression among the groups studied. Strong stromal expression of MMP-9 in ameloblastoma compared with tooth germ mesenchyme indicated the possibility of tumor induction with release of growth factors and cytokines, resulting in invasiveness of ameloblastoma. Epithelial TIMP-2 expression was associated with the least and most aggressive behavior of follicular and granular cell ameloblastoma, respectively. Stromal TIMP-2 expression reflected its role in regulating tumor progression in ameloblastoma and in regulating developmental processes in tooth germs by their inhibitory effect on MMP-9.
authors.affiliation: Department of Oral and Maxillofacial Pathology, Maulana Azad Institute of Dental Sciences, New Delhi, India.
authors.forename: Kalpana
authors.initials: K
authors.lastname: Nunia
authors.forename: Aadithya B
authors.initials: AB
authors.lastname: Urs
authors.forename: Priya
authors.initials: P
authors.lastname: Kumar
mesh_terms: D000564:Ameloblastoma / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D009024:Morphogenesis; D009805:Odontogenesis; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000378:metabolism*
chemical_list: D019716:Tissue Inhibitor of Metalloproteinase-2; D020780:Matrix Metalloproteinase 9