Immunohistochemical and ultrastructural investigation of apoptotic cell death in granular cell ameloblastoma

Abstract

Apoptotic cell death in granular cell ameloblastomas was examined by immunohistochemistry using anti-single-stranded DNA (ssDNA) antibody and transmission electron microscopy. Routinely prepared sections of granular cell ameloblastomas showed various quantities of granular cells with some apoptotic nuclear fragments. Immunoreactivity for ssDNA was higher in granular cells than in other neoplastic cells. Ultrastructural examination revealed abundant lysosomes in the cytoplasm of granular cells. Numerous apoptotic cell fragments with condensed nuclei in granular cell clusters were phagocytosed by adjacent granular cells. On immunohistochemical characterization of cellular differentiation, granular cells were positive for cytokeratin, CD68, lysozyme and alpha-1-antichymotrypsin, but negative for vimentin, desmin, S-100 protein, neuron-specific enolase and CD15, indicating epithelial origin and lysosomal aggregation. These features suggest that the cytoplasmic granularity in granular cell ameloblastomas might be caused by increased apoptotic cell death of neoplastic cells and associated phagocytosis by neighboring neoplastic cells.

Detection of Beclin1 and ATG5 in ameloblastic tumors

“…Ultrastructurally, abundant cytoplasmic lysosomes have been identified in granular neoplastic cells of granular cell tumors and granular cell ameloblastomas (22,(37)(38), and immunohistochemical examination has shown expression of lysosome-related antigen CD68 in granular cells of both of these tumor types (22,(38)(39). Our previous studies have confirmed increased apoptotic cell death and decreased expression of apoptosis suppressors in granular neoplastic cells of granular cell ameloblastomas (20)(21)(22)(23). In the present study, immunoreactivity for Beclin1 and ATG5 was found in granular neoplastic cells in granular cell ameloblastomas as well as in granular cell tumors.…”

“…Previous studies have confirmed the presence of apoptotic cells, apoptosis signaling molecules, and their modulators in tooth germs and ameloblastic tumors, suggesting that apoptotic cell death has an important role in oncogenesis or cytodifferentiation of odontogenic epithelium (4,(17)(18)(19)(20)(21)(22)(23). In the present study, expression of Beclin1 and ATG5 was examined in benign and malignant ameloblastic tumors as well as in tooth germs and granular cell tumors by reverse transcriptase-polymerase chain reaction (RT-PCR), Western blotting, and immunohistochemistry to evaluate the roles of these autophagy-related molecules in epithelial odontogenic tumors.…”

Granules in Granular Cell Lesions of the Head and Neck: A Review

“…On immunohistochemical characterization of cellular differentiation, granular cells are positive for cytokeratin, CD68, lysozyme, and alpha-1-antichymotrypsin, but negative for acid phosphatase, α-naphthyl acetate, β-glucuronidase, vimentin, desmin, S-100 protein, neuron-specific enolase, and CD15, indicating epithelial origin and lysosomal aggregation. These features suggest that the cytoplasmic granularity in GCA might be caused by increased apoptosis and associated phagocytosis by neighbouring neoplastic cells [3,8].…”

“…It is also postulated that residual ectomesenchymal influence may be responsible for proliferation of both gingival epithelium and mesenchymal cells which are subsequently transformed into granular cells [10,11]. Kumamoto and Ooya reported that granular cells are of epithelial origin and the result of processes of an involuted and dystrophic nature [8]. The granular cells are positive for vimentin, CD68, lysozyme, muscle-specific actin, alpha-smooth muscle actin, calponin, neuron-specific enolase (NSE), CD138, and bcl-2 [12].…”

Molecular alterations in the development and progression of odontogenic tumors

“…There are two alternative apoptotic pathways, one mediated by death receptors and the other by mitochondria, and apoptotic processes are modulated by a large family of genes, such as the tumor necrosis factor (TNF) family, the Bcl-2 family, and the inhibitor of apoptosis protein (IAP) family. In some epithelial odontogenic tumors, apoptotic cells have been detected by TdT-mediated dUTP-biotin nick end-labeling (TUNEL) and immunohistochemistry using single-stranded DNA (ssDNA) antibody, suggesting that apoptotic cell death plays an important role in oncogenesis and cell differentiation in odontogenic epithelium (4)(5)(6)(7)(8)(9)(10).…”