In situ hybridisation and immunocytochemical localisation of osteolytic cytokines and adhesion molecules in ameloblastomas

Ameloblastomas produce interleukin-1-like activity that could explain some part of their osteolytic capability. However, the cellular source of this osteolytic activity is unknown. In the present study, cytokines with known inflammatory and osteolytic activity, i.e., interleukin-1 (IL-1), tumour necrosis factor (TNF), and interleukin-6 (IL-6), have been localised by immunocytochemistry and in situ hybridisation. The cellular adhesion receptors ICAM-1, E-selectin and VCAM-1 have also been immunolocalised. Immunocytochemistry demonstrated that all seven specimens showed positive staining for IL-1α and IL-6 with these cytokines being located in the stellate reticulum-like cells and vascular endothelium. Very faint staining for IL-1β was seen in four of seven specimens. No reaction was seen for TNF-α. All specimens demonstrated E-selectin staining in the vascular endothelium and ICAM-1 and VCAM-1 staining in the stellate reticulum-like cells and the endothelium. In situ hybridisation for the cytokines showed the presence of mRNA of both IL-1α and IL-6 in the stellate reticulum-like cells. Faint staining for IL-1β was also seen. No staining was seen for TNF. These findings show that ameloblastomas synthesize two bone-modulating cytokines, IL-1α and IL-6, and that these are synthesized mainly by the stellate reticulum-like cells. These tumours also contain a proportion of activated blood vessels in which endothelial cells express the cellular adhesion receptors ICAM-1, E-selectin and VCAM-1.