Braz Dent J 23(2) 2012Proliferation and apoptosis in odontogenic tumors 91 INTRODUCTIONAmeloblastoma (AM) is a locally invasive benign epithelial odontogenic tumor that may arise from rests of dental lamina, enamel organ rests, cell rests, the epithelial lining of an odontogenic cyst or from the basal cell layer of oral mucosa (1). Its occurrence varies from 10% to 45.2% of all odontogenic tumors and reaches approximately 1% of all oral cavity neoplasms (2). The usual clinical presentation includes a painless swelling with expansion of the jaws. It can be classified in 3 main groups: solid or multicystic ameloblastoma, unicystic and peripheral. Among these, the solid type is more common and histopathologically represented by follicular, plexiform, acanthomatous, desmoplastic, granular and basal cell patterns (3). A high proliferative activity of the odontogenic epithelium in ameloblastoma (AM) and keratocystic odontogenic tumor (KOT) has been demonstrated. However, no previous study has simultaneously evaluated cell proliferation and apoptotic indexes in AM and KOT, comparing both lesions. The aim of this study was to assess and compare cell proliferation and apoptotic rates between these two tumors. Specimens of 11 solid AM and 11 sporadic KOT were evaluated. The proliferation index (PI) was assessed by immunohistochemical detection of Ki-67 and the apoptotic index (AI) by methyl green-pyronine and in situ DNA nick end-labelling methods. KOT presented a higher PI than AM (p<0.05). No statistically significant difference was found in the AI between AM and KOT. PI and AI were higher in the peripheral cells of AM and respectively in the suprabasal and superficial layers of KOT. In conclusion, KOT showed a higher cell proliferation than AM and the AI was similar between these tumors. These findings reinforce the classification of KOT as an odontogenic tumor and should contribute to its aggressive clinical behavior. Cell Proliferation and Apoptosis in Ameloblastomas and Keratocystic Odontogenic Tumors

On the basis of our findings, H3F3A p.Gly34 Trp or p.Gly34 Leu mutations are not a frequent event in CGCL. If these alterations are confirmed to be exclusive of GCT, the assessment of H3F3A mutations may help in the differential diagnosis of GCT and CGCL of the jaws.

The development of giant cells lesions of the jaws and cherubism are possibly mediated by overexpression of NFAT in the nucleus of the multinucleated cells.

Central giant cell lesion (CGCL) and peripheral giant cell lesion (PGCL) of the jaws are characterized by multinucleated osteoclast-like giant cells in a background of mononuclear cells. While mononuclear cells retain proliferative activity in both lesions, giant cells are Ki-67 negative. This observation raised the theory that giant cells are formed by cytoplasmic fusion of mononuclear cells, and also that these lesions are of reactive nature. As the giant cells are not proliferating in CGCL and PGCL, apoptosis of such cells should be investigated. We investigated the transcription of BAX and BCL-2 mRNAs in six fresh samples of CGCL and six fresh samples of PGCL by qRT-PCR (quantitative reverse transcription PCR) and used immunohistochemistry to demonstrate the localization of these proteins, as well as caspase 3 active in six paraffin-embedded samples of CGCL and nine paraffin-embedded samples of PGCL. While both groups showed increased expression of BAX and BCL-2 mRNA, PGCL showed a higher apoptotic index (ratio BAX/BCL-2) than CGCL. The three proteins investigated were expressed almost exclusively in the cytoplasm of giant cells. To further confirm apoptotic activity, we performed TUNEL analysis in the same samples of the immunohistochemistry and found a higher positivity in the giant cells of PGCL compared to the giant cells of CGCL. Our results show increased expression of apoptotic-related genes in both PGCL and CGCL and that the giant cells are probably the main source of these events. Also, it raises a hypothesis that differences in the apoptotic activity might be associated with the different clinical behavior of CGCL and PGCL.

Abstract.A variety of diseases of the jaws may present multinucleated giant cells. These diseases include central giant cell lesions (CGCL), peripheral giant cell lesions (PGCL), brown tumor of hyperparathyroidism (BTH), and cherubism. The multinucleated giant cells in these lesions are osteoclast-like. Since NFATc1 plays a significant role in osteoclast differentiation, the present study aimed to compare the expression of NFATc1 in CGCL, PGCL, BTH and cherubism. A total of 14 formalin-fixed and paraffin-embedded tissue samples of CGCL (n=4), PGCL (n=5), BTH (n=3) and cherubism (n=2) were included in the study. An immunohistochemical analysis was performed to investigate the NFATc1 protein.The majority of giant cells in all of the cases were positive for nuclear NFATc1 and the immunostaining pattern was similar in all of the groups. Although our study supports the hypothesis that giant cell accumulation in PGCL, CGCL, BTH and cherubism is mediated by NFATc1, functional studies are required to investigate this hypothesis.

The glycogen storage disease (GSD) is a group of inherited disorders that involve deficiencies in the enzymes that metabolize glycogen. The purpose of the present paper is to report a rare case of GSD type 1b that presented both peripheral and central giant cell granuloma, and to discuss the possible explanation for this unusual finding. The use of corticosteroids in the management of central giant cell granuloma is also demonstrated.

Despite the importance of clonality to understand the pathogenesis and progression of tumors, it has not been investigated yet in giant cell lesions of the jaws. The aim of this study was to analyze the clonality of peripheral giant cell lesions (PGCL) and central giant cell lesions (CGCL) of the jaws. Six samples of PGCL and 5 samples of CGCL were analyzed in this study using the polymorphic human androgen receptor locus (HUMARA) assay. Three out of the 5 samples of the CGCL and 3 out of 6 samples of PGCL exhibited a monoclonal pattern. Our findings demonstrate that some giant cell lesions of the jaws are clonal, which indicate that these lesions may have a common genetic mechanism of development. Further studies are necessary to better elucidate the molecular mechanisms involved in the pathogenesis of such lesions.

These results showed increased expression of WWOX mainly in non-aggressive GCLs of the jaws.