Local invasiveness of ameloblastoma. Role played by matrix metalloproteinases and proliferative activity

Aims: Ameloblastoma is an odontogenic neoplasm characterized by local invasiveness and recurrence. In this study we analysed the role played by matrix metalloproteinases (MMPs) in the local invasiveness of ameloblastoma. We also attempted to establish a relationship between the presence of MMPs and the proliferative activity of ameloblastoma cells. Methods and results: Immunohistochemistry was carried out to detect different MMPs in formalin-fixed paraffin-embedded samples of human ameloblastoma. Immunohistochemistry, however, does not establish whether a given MMP is latent or active. To address this point, we carried out biochemical methods, namely zymography and Western blotting. Our results showed expression of latent and active forms of MMPs 1, 2 and 9 in ameloblastoma. These enzymes may digest bone matrix and release mitogenic factors, which would increase tumour proliferation. This possibility prompted us to study the proliferation of ameloblastoma cells located in close proximity to bone. Silver-stained nucleolar organizer region morphometry revealed that ameloblastoma cells in the vicinity of bone show increased proliferation, when compared with controls. Conclusions: Our results suggest an interdependent mechanism involving MMPs and proliferation of ameloblastoma cells, which may contribute to the local invasiveness of this tumour.