Co-expression of BMP-2 and -7 in the Tumoral Epithelium of CEOT with Selective BMP-7 Expression in Amyloid Materials

Abstract

The calcifying epithelial odontogenic tumor (CEOT) is a benign but locally-invasive odontogenic neoplasm believed to take origin from the stratum intermedium of the developing tooth germ. Bone morphogenetic proteins (BMPs) are multifunctional signaling molecules that regulate diverse cellular processes including epithelial-mesenchymal interactions during odontogenesis. Aberrant BMP activity has been enumerated in the ameloblastoma but information about its distribution in the CEOT remains limited. The aim here was to investigate BMP expression in CEOT and to speculate on its significance. Immunolabelling for BMP-2 and BMP-7 was performed on archival tissues of six CEOT cases and the level of expression was quantified as negative (0), mild (+), moderate (2+) and strong (3+). Results disclosed that CEOT epithelium demonstrated co-expression of BMP-2 and -7 suggesting upregulation of these proteins at sites of tumor differentiation. Distribution patterns were distinct with some overlap. Their localizations were largely membranous and/or cytoplasmic. Amyloid-like materials strongly expressed BMP-7 but were nonreactive for BMP-2, implicating that these signaling proteins play differential roles in the formation of these extracellular products. Mineralized substances including Liesegang rings were mostly negative for both BMPs suggesting that calcification process is associated with repression of these molecules. Stromal endothelium and fibroblasts were stained variably positive. BMP was heterogeneously detected in the CEOT epithelium at the tumor advancing front suggesting their upregulation at active sites and downregulation in quiescent areas. Present findings suggest that BMP-2 and BMP-7 most likely play differential roles in the cellular differentiation and progression of CEOT. BMP-7 accumulation within amyloid-like protein is a novel finding.