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.