The goal of this study was to investigate the immunolocalization of inositol 1,4,5-trisphosphate receptor (IP3R) and vacuolar ATPase (V-ATPase) in ameloblastomas with special attention to the invasive front. Thirty-seven cases of previously diagnosed formalin-fixed paraffin-embedded (FFPE) human ameloblastoma samples were selected for this study. The samples were grouped according to the predominant histologic pattern and comprised twelve plexiform, eighteen follicular, and seven unicystic ameloblastomas. Of the unicystic variants, six demonstrated purely luminal and intraluminal growth, and one displayed mural extension. One granular cell variant was included in the follicular ameloblastoma group. All specimens were evaluated for IP3R and V-ATPase expression by immunohistochemistry (IHC). IP3R was positive in columnar cells, similar to ameloblasts, and non-peripheral cells in all samples. In the area of tumor protrusion and front of invasion, membranous and cystoplasmic IP3R expression was observed. In contrast, areas adjacent to tumoral protrusion demonstrated only membranous staining patterns. V-ATPase was not expressed in peripheral columnar cells of the unicystic and granular cell variants of ameloblastoma; however, strong staining was present in these cells in plexiform ameloblastomas, follicular ameloblastomas, and areas of mural growth of unicystic ameloblastomas. In areas of tumor protrusion, reactivity for V-ATPase was observed with both membranous and cytoplasmic staining, while other areas showed only membranous V-ATPase. These findings suggest that concomitant immunolocalization of IP3R and V-ATPase, with both cytoplasmic and membranous expression in the peripheral columnar cells, may indicate the invasive potential of ameloblastomas. Furthermore, these results suggest the tumoral spread of ameloblastomas may be correlated with the autophagy process and channelopathy. The expression of these proteins could establish a baseline for future research and provide therapeutic targets for treatment of ameloblastomas.
Keywords: Ameloblastoma; IP3R; Invasiveness; V-ATPase.