颌骨巨细胞瘤和巨细胞肉芽肿病变中多核巨细胞性质的探讨

目的 探讨颌骨巨细胞瘤(Giant cell tumor，GCT)和巨细胞肉芽肿(Giant cell granuloma，GCG)病变中多核巨细胞(Multinucleated giant cells，MGCs)的性质及组织来源。方法 对8例颌骨GET和8例GCG(中心性4例、外周性4例)进行酶组织化学和免疫组织化学观察，并与其它含MGICs的口腔病变(如异物反应、淋巴结结核等)进行比较。结果 颌骨GCT和GCG中的MGCs既可表达组织细胞／单核巨噬细胞相关抗原[如CD68、αl-抗胰蛋白酶(Alpha-1-antitrypsin，AAT)、α1-抗糜蛋白酶(Alpha-1-antichymotrypsin，AACT)、溶菌酶等]，又具有破骨细胞特异性酶-抗酒石酸酸性磷酸酶[Tartrate-resistant acid phosphatase(TRAP)]的活性，但不表达增殖细胞标记Ki-67抗原。结论 颌骨GCT和GCG中的MGCs可能是反应性终末分化细胞，由病变中处于不同分化阶段的前体破骨细胞融合而成．同时具有单核巨噬细胞和破骨细胞的某些表型特征。     

Peripheral giant cell granuloma. An immunohistochemical and ultrastructural study

OBJECTIVE: To study the nature of multinucleated and mononuclear cells from peripheral giant cell granuloma (PGCG).
MATERIALS AND METHODS: Formalin-fixed, paraffin-embedded sections of 40 cases of PGCG were immunohistochemically stained for vimentin, alpha I-antichymotrypsin, CD68, S-100 protein, lysozyme. leucocyte common antigen (LCA), factor VIII-retated antigen and muscle cell actin. Six cases of PGCG were also studied by transmission etectron microscopy.
RESULTS: Vimentin, alpha I-antichymotrypsin and CD68 were expressed in both the mononuclear and multinucleated giant cells. Dendritic mononuclear cells, positive for 5–100 protein, were noted in 67.5% of the lesions, whereas lysozyme and leucocyte common antigen were detected in occasional mononuclear cells. Ultrastructural examination showed mononuclear cells with signs of phagocytosis and sometimes interdigitations with similar cells. Others presented non-specific characteristics and the third type exhibited cytoplasmic processes and occasional Birbeck granules. Some multi-nucleated giant cells showed oval nuclei, abundant mitochondria and granular endoplasmic reticulum whereas others presented with irregular nuclei and a great number of cytoplasmic vacuoles.
CONCLUSIONS: lmmunohistochemical and ultrastructural results suggest that PGCGs of the jaws are composed mainly of cells of the mononuclear phagocyte system and that Langerhans cells are present in two thirds of the lesions.     

Expression of receptor activator of NF‐κB ligand and osteoprotegerin in peripheral giant cell granulomas of the jaws

J Oral Pathol Med (2010) 39 : 687–689 Background: Peripheral giant cell granuloma is a tumor of the jaw characterized by the presence of multinucleated giant cells and mononuclear cells within a fibrous stroma. These lesions are considered to be of a reactive nature rather than neoplastic. Although peripheral giant cell granulomas is a well‐described clinical entity, little is known on its pathogenesis. The aim of this study was to investigate the receptor activator of NF‐κB ligand (RANKL) and osteoprotegerin (OPG) expression and immunolocalization in giant cell granulomas. Methods: RANKL and OPG protein expression was evaluated in 22 peripheral giant cell granulomas samples, by means of immunohistochemistry. Staining was evaluated semi‐quantitatively, according to the extent and intensity of the stain. Results: RANKL was expressed in all cases with a cytoplasmic staining pattern, whereas OPG expression was detected in 21 of the 22 cases examined. Active multinucleated giant cells exhibited intense immunoreactivity for both proteins. Conclusion: RANKL and OPG are expressed in peripheral giant cell granulomas of the jaw in a manner supporting the osteoclastic nature of giant cells whereas the possible osteoclastic lineage of stromal monocytes remains ambiguous.     

31例颌骨中心性巨细胞肉芽肿的临床病理研究

目的 观察分析颌骨中心性巨细胞肉芽肿(CGCG)的临床病理学特点及病变生物学行为问的关系，探讨颌骨CGCG的性质及诊断。方法 采用组织病理学方法，结合临床随访对比分析31例颌骨CGCG的临床病理学特点及其与病变性质的关系。结果 31例颌骨CGCG以30岁以下的女性多见，病变多见于下颌，X线表现无特异性。病变中的多核巨细胞(MGC)分布较不均匀，核数较少，以10～19个核多见，病变出血明显，纤维成分丰富，常有含铁血黄素沉积，骨及类骨质多见。比较病变复发组与非复发组问的临床病理学特点，结果提示差异无统计学意义。根据临床和X线特点病变分为侵袭组与非侵袭组，侵袭组与复发关系密切。结论 颌骨CGCG是一种非瘤性病变，在病变性质上有别于骨巨细胞瘤，其病理学特点在两者的鉴别上缺乏客观标准并且与其生物学行为无关，结合临床分析对治疗更加有意义。     

Giant Cell Lesions of the Jaws Involving RASopathy Syndromes

ObjectiveGiant cell lesions of the jaws (GCLJ) may rarely occur in the setting of RASopathy syndromes such as Noonan syndrome or neurofibromatosis I. Recently, central giant cell granulomas (CGCG), the most common of the GCLJ, have been recognized as benign neoplasms characterized by Ras/MAPK signaling pathway mutations. This provides a rational basis for understanding GCLJ in RASopathy syndromes as syndromically occurring CGCG. This review aims to summarize the clinicopathologic features of syndromic CGCG and to review the salient clinical and craniofacial features of the syndromes in which they may rarely occur.Material and MethodsAn electronic search in 3 databases was performed, looking for GCLJ/CGCG in RASopathy syndromes.Results124 CGCG in 56 patients were identified across 6 RASopathy syndromes. Median age at syndromic CGCG diagnosis is 11 years; 69.6% (39/56) patients developed two or more CGCG; 58.9% (33/56) presented with bilateral posterior mandibular CGCGs, mimicking cherubism. Of 88 CGCG with follow-up, 22.4% (13/58) of excised/resected CGCG recurred while 46.7% (14/30) of monitored CGCG showed continued growth.ConclusionSyndromic CGCG involves multiple RASopathy syndromes and may mimic cherubism or, when solitary, sporadically occurring CGCG. Familiarity with other clinical findings of RASopathy syndromes is critical for appropriate diagnosis and patient management.     

破骨细胞分化因子和骨保护因子在颌骨中心性巨细胞病变组织中的表达

目的 检测破骨细胞核因子κB受体活化因子配体(RANKL，又称破骨细胞分化因子)和骨保护因子(OPG)蛋白在颌骨中心性巨细胞病变中的表达，探讨此类病变发生骨破坏的作用机制。方法采用免疫组织化学的方法检测26例颌骨中心性巨细胞病变中RANKL和OPG蛋白的表达。结果 RANKL在颌骨中心性巨细胞病变中的血管、基质中有强烈表达，某些病变中的部分短梭形单核基质细胞和多核巨细胞的胞膜也为RANKL阳性；病变中大部分的多核巨细胞和少部分圆形单核基质细胞的胞质OPG表达为阳性。结论 激活的血管内皮细胞通过调节RANKL的表达来促进颌骨中心性巨细胞病变中的多核破骨样巨细胞的形成；RANKL可以通过旁分泌和自分泌的方式发挥作用。同时在颌骨中心性巨细胞病变中存在由OPG介导的抑制多核破骨样巨细胞生成和骨吸收的负反馈机制。     

Peripheral and central giant cell granulomas of the jaws: a retrospective study and surgical management

This 18-year retrospective multi-center study analyzed data from patients diagnosed and treated for peripheral giant cell granuloma (PGCG) and central giant cell granuloma (CGCG) of the jaws from 1991-2009. Data included age, gender, the jaw involved, the area of the lesion, the type of surgical treatment, and recurrence. Thorough curettage or partial resection was used to treat CGCG (96.39% success rate) and PGCG (98.71% success rate) in this group of patients documented during the follow-up period (1-18 years).     

PCNA and Ki-67 immunoreactivity in multinucleated cells of giant cell fibroma and peripheral giant cell granuloma

Immunohistochemical investigation of PCNA and Ki-67, two diverse nuclear proteins essential to the cell cycle, was undertaken in archival, formalin-fixed and paraffin-embedded specimens of giant cell fibroma (GCF) and peripheral giant cell granuloma (PGCG). GCF multinucleated cell nuclei were mostly PCNA⁺, although there was variability in staining intensity. This indicates heterogeneity in nuclear PCNA metabolism of GCF multinucleated cells, and it is possible that the most intensely stained nuclei have passed through the cell cycle more recently compared to the less immunoreactive nuclei. However, the absence of Ki-67 immunoreactivity in GCF multinucleated cells, and absence of mitoses in GCF multinucleated cells, suggests that cell cycling in the absence of cytokinesis is not involved in GCF multinucleated cell formation. Alternatively, GCF multinucleated cells possibly form by fusion of mononuclear cells previously identified as fibroblasts, although this theory cannot be confirmed by the data presented in this study, and the histogenesis of GCF multinucleated cells remains unclear. In contrast, absence of either PCNA or Ki-67 immunoreactivity in PGCG multinucleated cells is consistent with an osteoclast lineage and formation from differentiated mononuclear cells.     

Quantitative analysis of argyrophilic nuclear organizer regions in giant cell lesions of jaws

J Oral Pathol Med (2010) 39 : 431–434 Background: Giant cell lesions of the jaws are considerably similar according to histopathologic characteristics yet show different clinical behaviors. These lesions include central giant cell granuloma (CGCG), aneurysmal bone cyst, Cherubism, and Brown tumor associated with hyperparathyroidism. The present study aimed to investigate AgNORs count in these lesions as a proliferative marker and to determine whether it can be used to discriminate between them or not. Methods: Forty‐one cases of giant cell lesions of jaws were retrived from Oral Pathology Department (1987–2007). They included 21 cases of CGCG, eight cases of aneurysmal bone cyst (ABC), six cases of Cherubism, six cases of Brown tumor. The mean AgNORs count was calculated for all cases. To compare mean AgNORs in groups of lesions, ANOVA test was performed. Results: Mean AgNOR counts were: (0/85 ± 0/29) in CGCG, (0/76 ± 0/32) in ABC (0/87 ± 0/10) in Cherubism and (0/82 ± 0/16) in Brown tumor. A significant difference was not observed in AgNOR counts among these groups of lesions. Conclusions: Jaws giant cell containing lesions have no acceptable differences in mean AgNORs.     

SH3BP2-encoding exons involved in cherubism are not associated with central giant cell granuloma

Central giant cell granuloma (CGCG) is a benign lesion with unpredictable biological behaviour ranging from a slow-growing asymptomatic swelling to an aggressive lesion associated with pain, bone and root resorption and also tooth displacement. The aetiology of the disease is unclear with controversies in the literature on whether it is mainly of reactional, inflammatory, infectious, neoplasic or genetic origin. To test the hypothesis that mutations in the SH3BP2 gene, as the principal cause of cherubism, are also responsible for, or at least associated with, giant cell lesions, 30 patients with CGCG were recruited for this study and subjected to analysis of germ line and/or somatic alterations. In the blood samples of nine patients, one codon alteration in exon 4 was found, but this alteration did not lead to changes at the amino acid level. In conclusion, if a primary genetic defect is the cause for CGCG it is either located in SH3BP2 gene exons not yet related to cherubism or in a different gene.     

Immunohistochemical expression of p53, MDM2, Ki-67 and PCNA in central giant cell granuloma and giant cell tumor

Central gaint cell granuloma (CGCG) is a reactive bone lesion that occurs mainly in the jaws. The gaint cell tumour (GCT) is a benign locally aggressive neoplasm located near the articular end of tubular bones. Both lesions are characterised histologically by multinucleated gaint cells in a background of ovoid to spindle-shaped mesenchymal cells. There is a basic question whether both lesions are separate entities or variants of the same disease. The study of cell cycle-associated proteins may give insights into clarifing such question. The expression of these protiens is also important to determine the cell cycle regulation in both tumours. The purpose of this study was to evaluate the immunohistochimical expression of p53, MDM2, Ki-67 and PCNA in CGCG and GCT. The results demonstrated that, despite the lack of p53 immunoreactivity, all the samples showed wide expression of MDM2. The percentage of Ki-67-and PCNA-positive cell in CGCG was statistically higher than that of GCT. Our findings shwo that CGCG has a higher proliferative activity compared with that of the GCT. Our results also suggest that p53 inactivation by MDM2 expression may be involved in the pathogenesis of gaint cell lesions of the jaws and long bones.     

A comparative immunohistochemical evaluation of CD68 and TRAP protein expression in central and peripheral giant cell granulomas of the jaws

J Oral Pathol Med (2011) 40 : 334–337 Background: Giant cell granulomas of the jaws are lesions that arise either peripherally in periodontal ligament and mucoperiosteum or centrally in the bone. The aim of this study was to evaluate expression of CD68 and tartrate‐resistant acid phosphatase (TRAP) proteins in multinucleated giant cells and mononuclear cells. Methods: Formalin‐fixed and paraffin‐embedded tissue section of 20 specimens of central giant cell granuloma and 20 cases of peripheral giant cell granuloma were immunohistochemically analyzed for CD68 and TRAP proteins expression rate using Biotin‐Streptavidin method. Result: In central giant cell granuloma, more than 99% of multinucleated giant cells were positive for TRAP antibody and about 90% were positive for CD68. In mononuclear cells of this lesion, 14% of cases were positive with TRAP antibody and 8% with CD68. In peripheral giant cell granuloma, TRAP antibody was positive in 99% of giant cells and in 13% of mononuclear cells. A proportion of 97% of giant cells and 6% of mononuclear cells reacted positively with CD68. Conclusion: Immunohistochemical evidence of this study shows that giant cells and a group of mononuclear cells of stroma in both peripheral and central giant cell granuloma express TRAP antibody severely that is specific for osteoclast. Also, these cells are positive reactive to CD68, which is the macrophage marker and therefore it can be mentioned that giant cells are osteoclast, although their origins are macrophagic/monocytic or their precursors, and maybe mononuclear cells in stroma have a role in formation of giant cells.     

Cellular mechanisms of osteoclast formation and lacunar resorption in giant cell granuloma of the jaw

BACKGROUND: Giant cell granuloma (GCG) is an osteolytic tumour of the jaw which is characterised by the presence of both mononuclear and multinucleated (osteoclast-like) giant cell components. The nature of these component cells and the pathogenesis of the extensive osteolysis associated with this lesion is uncertain. METHODS: Using cell culture techniques and immunohistochemistry, we defined the phenotypic characteristics of the mononuclear and multinucleated cells present in four cases of GCG of the jaw. We also analysed the cellular and humoral factors associated with osteoclast formation and osteolysis in these tumours and determined whether GCG stromal cells are capable of supporting osteoclast formation. RESULTS: GCG-derived giant cells expressed the phenotypic characteristics of osteoclasts (TRAP+, VNR+, and calcitonin responsive) and were capable of lacunar resorption. In addition to macrophages, the mononuclear cell population contained numerous spindle-shaped stromal cells which proliferated in culture and expressed RANKL; these GCG-stromal cells were capable of supporting human osteoclast formation from circulating monocyte precursors. CONCLUSION: Our findings indicate that the giant cells in GCG of the jaw are osteoclast-like and formed from monocyte/macrophage precursors which differentiate into osteoclasts under the influence of RANKL-expressing mononuclear stromal cells found in this lesion.     

RANK, RANKL and OPG expressions in a permanent molar with a replacement resorption

The aim of this study was to explore the expression of RANK, RANKL and OPG during ankylosis. Structural details and immunohistochemical investigations of the expression of RANK, RANKL and OPG in an extracted secondary retained permanent molar of a 12-year-old girl are reported. Woven and lamellar bones were observed in the thickness of the remodeled dental wall and a tertiary dentin was noticed around the pulp cavity. The resorbing multinucleated cells expressed TRAP and RANK but few of them also expressed RANKL. Both odontoblasts and osteoblasts expressed TRAP and RANK, but the expression of RANKL was limited to osteoblasts. OPG remained undetected. The present case reveals unusual expression of RANKL in the resorbing cells, TRAP and RANK in both osteoblasts and odontoblasts, and a failure of detection of OPG. These proteins could be involved in the pathogenesis of tooth ankylosis.     

High extracellular calcium affects osteoclastogenesis in mouse bone marrow cell culture

The effects of high extracellular calcium (high Ca) in the local microenvironment on osteoclasts, osteoclast progenitors and stromal cells are not fully understood. We examined high Ca effect on osteoclastogenesis in mouse bone marrow cell culture. Mouse bone marrow cells were cultured for up to 6 days in the medium supplemented with 1, 25(OH)2 vitamin D3 (D3). High Ca treatment at the early stage of culture (the initial 24 hours) reduced the number of tartrate resistant acid phosphatase-positive multinuclear cells (TRAP(+)MNCs). This treatment slightly up-regulated the mRNA expressions of receptor activator of NF-(B ligand (RANKL), RANK and osteoprotegerin (OPG). This inhibitory effect on the formation of TRAP(+)MNCs was recovered by RANKL. In contrast, high Ca treatment at the later stage of osteoclastogenesis (the last 2 days of culture) stimulated the formation of TRAP(+)MNCs, increased RANKL and RANK mRNA expressions and decreased OPG mRNA. High Ca at neither the early nor the later stage of culture affected the total number of adherent cells and the mRNA expression of alkaline phosphatase and osteopontin. In conclusion, high Ca affects osteoclastogenesis in a manner depending on the stage of osteoclastogenesis, which is partly mediated via the RANKL-RANK-OPG regulatory system.     

原位杂交与免疫组化检测c-Src在家族性巨颌症的表达

目的:探讨c-Src基因在家族性巨颌症中的表达及意义。方法:应用原位杂交方法与免疫组织化学技术检测12例家族性巨颌症病变组织中c-Src蛋白与c-Src mRNA的表达。结果:12例家族性巨颌症病变组织中的多核巨细胞、10%~15%的单核圆形基质细胞胞浆表达c-Src蛋白与mRNA,二者阳性细胞表达率无显著性差别,c-Src mRNA表达结果与c-Src蛋白相一致,二者呈正相关关系。结论:c-Src表达可能与家族性巨颌症病变中多核巨细胞的形成和破骨特性有关。     

Receptor activator NF kappaB ligand (RANKL) and osteoprotegerin (OPG) protein expression in periodontitis

OBJECTIVES AND BACKGROUND: This study investigated the expression of key mediators that regulate differentiation of osteoclasts, receptor activator of nuclear factor kappaB ligand (RANKL), and its natural inhibitor, osteoprotegerin (OPG), in periodontitis. We aimed to compare the levels of the RANKL and OPG in the granulomatous tissue adjacent to areas of alveolar bone loss from patients with periodontitis to that present in tissue from patients without periodontitis. In addition, we aimed to determine the types of cells expressing these factors in these tissues and to demonstrate the expression of the osteoclastic markers, RANK and tartrate-resistant acid phosphatase (TRAP), in periodontitis. MATERIALS AND METHODS: Frozen biopsy specimens were analysed using specific monoclonal antibodies and were evaluated by semiquantitative analysis and digital image analysis to compare levels of RANKL and OPG protein expression. Double labelling of frozen sections with antibodies to different cell lineage specific markers was used to determine the types of cells expressing these proteins. In situ hybridization was used to detect cells expressing RANK mRNA. RESULTS: Semiquantitative image analysis demonstrated that significantly higher levels of RANKL protein (P < 0.05) were expressed in the periodontitis tissue. Conversely, OPG protein was significantly lower (P < 0.05) in the periodontitis tissues. RANKL protein was associated with lymphocytes and macrophages. OPG protein was associated with endothelial cells in both tissues. Many leukocytes expressing RANK mRNA and TRAP were observed in periodontitis tissues. CONCLUSION: The change in the levels of these key regulators of osteoclast differentiation may play a major role in the bone loss seen in periodontitis.     

小鼠牙乳头来源MDPC-23细胞自发形成的类破牙细胞鉴定

目的探寻小鼠牙乳头来源MDPC-23细胞自发形成的体外破牙细胞的培养方法。 方法MDPC-23细胞常规培养6 d,利用抗酒石酸酸性磷酸酶（TRAP）染色法与RANKL诱导RAW 264.7细胞形成的破骨细胞相比较;金相显微镜及扫描电镜（SEM）观察牙本质片上细胞形态及吸收陷窝形成情况;免疫荧光染色观察丝状肌动蛋白（F-actin）细胞骨架结构;免疫印迹、免疫荧光和（或）ELISA法检测破牙细胞形成相关蛋白RANKL、RANK、TRAF6以及破牙细胞标志蛋白TRAP、组织蛋白酶K（Cathepsin K）的表达情况。Cathepsin K和TRAP蛋白表达的灰度值比较采用两独立样本的t检验进行统计;0、2、4、6 d四个时间点RANKL分泌水平的比较采用方差分析进行统计分析。 结果MDPC-23细胞常规培养6 d可自发形成少量TRAP染色阳性的多核巨细胞,其形态有别于RAW 264.7细胞形成的破骨细胞;自发形成的多核巨细胞仅能在牙本质片上形成少量较浅的吸收陷窝;免疫荧光结果显示,自发形成的类破牙细胞具有破牙细胞特征性丝状肌动蛋白环结构;免疫印迹、免疫荧光和（或）ELISA结果表明,MDPC-23细胞体外常规培养下表达RANK、TRAF6蛋白并自分泌RANKL,第0、2、4、6天RANKL分泌水平总体差异有统计学意义（F = 5.373,P = 0.026）,第2天RANKL分泌水平较第0天增加（P = 0.007）;第6天TRAP及Cathepsin K蛋白表达上调（t_TRAP = 5.033,P_TRAP = 0.0024;t_{Cathepsin K} = 12.95,P_{Cathepsin K} = 0.0002）。 结论MDPC-23细胞体外常规培养下可自发形成少量吸收能力较弱的TRAP染色阳性的多核巨细胞,具有特征性肌动蛋白环结构,同时能上调破牙细胞特征性蛋白TRAP和Cathepsin K表达,自分泌RANKL并表达RANK、TRAF6蛋白,是与成熟破牙细胞形态、结构及蛋白表达相似的类破牙细胞。     

The role of parathyroid hormone-related protein in the regulation of osteoclastogenesis by cementoblasts

BACKGROUND: Parathyroid hormone-related protein (PTHrP) promotes osteoclastogenesis by inhibiting expression of osteoprotegerin (OPG), a decoy receptor for the receptor activator of nuclear factor kappa B (RANK), and by enhancing production of RANK ligand (RANKL) by osteoblasts. However, little is known regarding the role of PTHrP in regulating cementoblast-mediated osteoclastogenesis. METHODS: This study determined the impact of PTHrP on osteoclastogenesis using: 1) OCCM-30 (immortalized murine cementoblasts), 2) RAW 264.7 cells (murine myeloid cells), or 3) OCCM-30 plus RAW 264.7 cells. Cells were treated with PTHrP (1-34), RANKL, or PTHrP and RANKL combined. Enzyme-linked immunosorbent assays (ELISAs) for OPG and RANKL were performed on media and cell lysates, and tartrate-resistant acid phosphatase (TRAP) and mRNA detection for the osteoclast associated receptor (OSCAR) were performed. RESULTS: The highest numbers of TRAP-positive cells and cells expressing OSCAR were found in the RAW cell group treated with either RANKL alone or RANKL and PTHrP. TRAP-positive cells were fewer when OCCM cells were co-cultured with RAW, but the greatest numbers were still with both PTHrP and RANKL. OPG levels were highest from OCCM cells and PTHrP decreased these levels. In contrast, RANKL levels were low in OCCM cell lysates and PTHrP increased RANKL. In vivo studies also revealed high osteoclastic activity surrounding developing teeth in mice administered PTH. CONCLUSIONS: These results demonstrate that PTHrP influences the balance of OPG and RANKL production by cementoblasts, and further indicate that this effect, in the context of surrounding cells, might have a significant impact on osteoclastogenesis, root resorption, and tooth eruption.     

Genetic profiling of central giant cell granuloma of the jaws

Central giant cell granuloma (CGCG) of the jaws is a central osteolytic lesion characterized histologically by multinucleated giant cells in a background of ovoid to spindle-shaped mesenchymal cells. Whether CGCG is a reactive lesion or a truly benign neoplasm remains undetermined, and the mechanism determining the onset of the disease remains unknown. To have more information regarding the genetic events involved in CGCG, the authors decided to perform an expression profile. Samples were derived from two surgically resected CGCG of the mandible. RNA extracted from a pool of three normal bone tissues was used as control. By using DNA microarrays containing 19,200 genes, the authors identified several genes whose expression was significantly up- or down-regulated. The differentially expressed genes cover a broad range of functional activities: cell cycle regulation; signal transduction; and vesicular transport. It was also possible to detect some genes whose function is unknown. The authors believe the data reported to be the first genetic portrait of CGCG of the jaws. Several markers have been identified that can potentially help in identifying some biological behavior (ie, quiescent versus aggressive lesions), as well as genes whose products could be potentially disease-specific targets for therapy. However, the authors think that more cases are needed, especially those comparing quiescent and aggressive lesions, before the exact profile of CGCG is known.