Immunohistochemical assessment of LGR5 and LGR6 in solid and unicystic ameloblastomas

Abstract

Objective: To explore the expression patterns of LGR5 and LGR6, putative stem cell-related markers that potentiate the Wnt signaling pathway, in ameloblastomas. Methods: Immunohistochemical staining for LGR5 and LGR6 was conducted on 55 odontogenic tissue samples, including 8 dental follicles and 47 ameloblastomas. Immunofluorescence staining for LGR5, β-catenin, and Ki-67 was conducted on follicular and unicystic ameloblastomas. Results: LGR5 and LGR6 immunoreactivity were detected in the cell membranes and cytoplasm of both non-neoplastic and neoplastic odontogenic epithelial cells in most dental follicle and ameloblastoma samples. In ameloblastomas, LGR5 and LGR6 were commonly expressed in peripheral neoplastic cells, and to a lesser extent, in central cells. In solid ameloblastomas, the acanthomatous and granular subtypes showed no LGR6 reactivity in keratinizing or granular cells. In contrast, the basal cell and desmoplastic subtypes expressed LGR5 and LGR6 in most neoplastic cells. Unicystic ameloblastomas showed LGR5 and LGR6 reactivity in neoplastic cells lining the cyst walls and other epithelial components, with a tendency for higher expression levels than in solid ameloblastomas. Immunofluorescence staining showed the co-expression of LGR5 with β-catenin and LGR5 with Ki-67. LGR5 was expressed on the cell membrane or in the cytoplasm, β-catenin was expressed on the cell membrane, and Ki-67 was expressed in the nucleus. Conclusions: Although LGR5 and LGR6 immunoreactivity in odontogenic tissues did not indicate a definitive association with stem cells, the findings suggest that these markers play a role in neoplastic tissue structuring and cell differentiation via modulation of the Wnt signaling pathway.