RESUMO
AIMS: Ameloblastoma AME is a benign tumour characterized by local invasiveness, high recurrence rates, and diverse histological patterns. The oxygen concentration is reduced in specific areas of the tumour microenvironment, which leads to intratumoral hypoxia. Crosstalk between NOTCH1, a disintegrin and metalloproteinase 12 (ADAM-12), hypoxia-inducible factor 1α (HIF-1α) and heparin-binding epidermal growth factor (HB-EGF) under hypoxic conditions has been implicated in invadopodia formation, tumour invasiveness, and metastasis development. The aim of this study was to analyse the expression of these proteins, in order to further elucidate the mechanisms underlying AME invasiveness. METHODS AND RESULTS: Twenty cases of AME, eight calcifying cystic odontogenic tumours CCOTs and 10 samples of dental follicle were used to investigate the expression of these proteins by immunohistochemistry with the primary antibodies anti-NOTCH1, anti-ADAM-12, anti-HIF-1α, and anti-HB-EGF. Immunostaining results were expressed as the percentage of stained area in images acquired in an AxioScope microscope equipped with an AxioCamHRc camera and a × 40 objective. The results showed that immunoexpression of all proteins was higher in the AME samples than in the CCOT and dental follicle samples (P < 0.05). CONCLUSIONS: AME showed an increased presence of proteins associated with tumour invasiveness, which indicates a possible role of these proteins in the biological behaviour of this tumour.
Assuntos
Proteína ADAM12/metabolismo , Ameloblastoma/metabolismo , Fator de Crescimento Semelhante a EGF de Ligação à Heparina/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Neoplasias Bucais/metabolismo , Cisto Odontogênico Calcificante/metabolismo , Receptor Notch1/metabolismo , Ameloblastoma/diagnóstico , Estudos de Coortes , Saco Dentário/metabolismo , Saco Dentário/patologia , Feminino , Humanos , Imuno-Histoquímica , Masculino , Neoplasias Bucais/diagnóstico , Invasividade Neoplásica , Cisto Odontogênico Calcificante/diagnóstico , Análise Serial de Tecidos , Hipóxia Tumoral , Microambiente TumoralRESUMO
BACKGROUND: Pilomatrixoma, craniopharyngioma, and calcifying cystic odontogenic tumor are the main entities presenting ghost cells as an important histological feature, in spite their quite different clinical presentation; it seems that they share a common pathway in the formation of these cells. The aim of this study is to examine and compare the characteristics of ghost and other cells that form these lesions. METHODS: Forty-three cases including 21 pilomatrixomas, 14 craniopharyngiomas, and eight calcifying cystic odontogenic tumors were evaluated by immunohistochemistry for cytokeratins, CD138, ß-catenin, D2-40, Glut-1, FAS, CD10 and also by scanning electron microscopy. RESULTS: The CKs, CD138, ß-catenin, Glut-1, FAS, and CD10 were more often expressed by transitional cells of craniopharyngioma and calcifying cystic odontogenic tumor, compared with pilomatrixoma. Basaloid cells of pilomatrixoma showed strong positivity for CD138 and CD10. Differences on expression pattern were identified in transitional and basal cells, as ghost cells were negative for most antibodies used, except by low expression for cytokeratins. By scanning electron microscopy, the morphology of ghost cells were similar in their fibrillar cytoplasm, but their pattern varied from sheets in pilomatrixoma to small clusters in craniopharyngioma and calcifying cystic odontogenic tumor. CONCLUSIONS: Mechanisms involved in formation of ghost cells are unknown, but probably they follow different pathways as protein expression in the basal/transitional cells was not uniform in the three tumors studied.
Assuntos
Craniofaringioma/patologia , Doenças do Cabelo/patologia , Neoplasias Maxilomandibulares/patologia , Cisto Odontogênico Calcificante/patologia , Tumores Odontogênicos/patologia , Pilomatrixoma/patologia , Neoplasias Hipofisárias/patologia , Neoplasias Cutâneas/patologia , Craniofaringioma/metabolismo , Craniofaringioma/ultraestrutura , Células Epiteliais/patologia , Transportador de Glucose Tipo 1/metabolismo , Doenças do Cabelo/metabolismo , Humanos , Imuno-Histoquímica , Neoplasias Maxilomandibulares/metabolismo , Neoplasias Maxilomandibulares/ultraestrutura , Queratinas/metabolismo , Microscopia Eletrônica de Varredura , Neprilisina/metabolismo , Cisto Odontogênico Calcificante/metabolismo , Cisto Odontogênico Calcificante/ultraestrutura , Tumores Odontogênicos/metabolismo , Tumores Odontogênicos/ultraestrutura , Pilomatrixoma/metabolismo , Pilomatrixoma/ultraestrutura , Neoplasias Hipofisárias/metabolismo , Neoplasias Hipofisárias/ultraestrutura , Neoplasias Cutâneas/metabolismo , Neoplasias Cutâneas/ultraestrutura , Sindecana-1/metabolismo , beta Catenina/metabolismo , Receptor fas/metabolismoRESUMO
OBJECTIVE: Benign and malignant tumor cells can express altered adhesion properties, and these features can be associated with their proliferative and invasive characteristics. This study aimed to evaluate syndecan-1 and Ki-67 expression in ghost cell-containing odontogenic tumors. STUDY DESIGN: Clinical data were retrieved from laboratory records, and hematoxylin-eosin-stained slides and sections, labeled with monoclonal antibodies anti-syndecan-1 and anti-Ki-67 using the immunoperoxidase technique, were evaluated. RESULTS: Included were 21 central calcifying cystic odontogenic tumors (CCOTs) (4 associated with odontoma), 2 peripheral CCOTs, 1 dentinogenic ghost cell tumor, and 1 ghost cell odontogenic carcinoma (GCOC). Syndecan-1 was mainly expressed in cells resembling stellate reticulum and in stromal cells from the fibrous capsule. The mean Ki-67 labeling index was 4.1% (49.3% for GCOC), but it was not associated with syndecan-1 expression. CONCLUSIONS: Syndecan-1 is variably expressed in cells resembling the stellate reticulum, stromal cells, and basal cells and might be associated with the biology of these tumors.
Assuntos
Neoplasias Maxilomandibulares/metabolismo , Antígeno Ki-67/metabolismo , Cistos Odontogênicos/metabolismo , Tumores Odontogênicos/metabolismo , Sindecana-1/metabolismo , Adolescente , Adulto , Biomarcadores Tumorais/metabolismo , Cisto Dentígero/metabolismo , Cisto Dentígero/patologia , Feminino , Humanos , Técnicas Imunoenzimáticas , Neoplasias Maxilomandibulares/patologia , Masculino , Cisto Odontogênico Calcificante/metabolismo , Cisto Odontogênico Calcificante/patologia , Cistos Odontogênicos/patologia , Tumores Odontogênicos/patologiaRESUMO
Calcifying cystic odontogenic tumors (CCOTs) are benign cystic lesions of odontogenic origin characterized by an ameloblastoma-like epithelium and the presence of a group of cells named ghost cells. The pattern of cytokeratin (Ck) expression on these lesions remains unclear and needs to be clarified. To this end, the expression of Ck6, Ck13, Ck14, Ck18, and Ck19 in the epithelium lining of 7 cases of CCOTs was evaluated by immunohistochemistry. For this, the epithelium lining was divided into 3 distinct regions: basal layer, suprabasal layer, and the compartment composed of ghost cells. In this study, 6 cases (85.7%) were classified as type 1 and 1 (14.3%) as type 4. All cases were negative for Ck13 and Ck18, despite the epithelial layer, as well as in the ghost cells. Ck6 was only positive in the ghost cells. Positivity for Ck14 and Ck19 was found in the basal and suprabasal layers, including the ghost cells. The results showing positivity for Ck14 and Ck19 in all of the analyzed cases reinforce CCOT as being of odontogenic origin, and the restricted expression of Ck6 in the ghost cells may be indicative that these cells suffer an altered differentiation into hair follicles in CCOTs.
Assuntos
Ameloblastoma/patologia , Neoplasias Maxilomandibulares/patologia , Queratinas/metabolismo , Cisto Odontogênico Calcificante/patologia , Tumores Odontogênicos/patologia , Adolescente , Adulto , Idoso , Ameloblastoma/metabolismo , Diferenciação Celular , Epitélio/metabolismo , Epitélio/patologia , Feminino , Folículo Piloso/metabolismo , Folículo Piloso/patologia , Humanos , Imuno-Histoquímica , Neoplasias Maxilomandibulares/metabolismo , Masculino , Pessoa de Meia-Idade , Cisto Odontogênico Calcificante/metabolismo , Tumores Odontogênicos/metabolismo , Adulto JovemRESUMO
OBJECTIVE: The objective of this preliminary study was to evaluate the expression of matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs) and growth factors in keratocystic odontogenic tumors (KOTs). STUDY DESIGN: The expression of MMPs, TIMPs, growth factors, and the extracellular signal-regulated kinase (ERK) 1/2 signaling pathway were assessed by immunohistochemistry in 15 cases of KOT and 4 cases of calcifying cystic odontogenic tumor (CCOT). RESULTS: KOT samples expressed significantly higher amounts of MMPs, TIMPs, growth factors, epidermal growth factor receptor (EGFR), and ERK compared with CCOT samples, with the exception of MMP-2 and TIMP-1. CONCLUSIONS: MMP-9, TIMP-2, EGF and transforming growth factor α act together and likely regulate the proliferation and aggressiveness of KOT. ERK-1/2 serves as the transducer of signals generated by these proteins, which signal through the common receptor, EGFR. This process may be related to the increased proliferation and aggressiveness observed in KOT.
Assuntos
Receptores ErbB/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Neoplasias Maxilomandibulares/metabolismo , Neoplasias Maxilomandibulares/patologia , Metaloproteinases da Matriz/metabolismo , Cisto Odontogênico Calcificante/metabolismo , Cisto Odontogênico Calcificante/patologia , Inibidores Teciduais de Metaloproteinases/metabolismo , Humanos , Técnicas Imunoenzimáticas , Estatísticas não ParamétricasRESUMO
AIMS: Ameloblastoma is an odontogenic neoplasm with local invasiveness and recurrence. We have previously suggested that growth factors and matrix metalloproteinases (MMPs) influence ameloblastoma invasiveness. The aim was to study expression of MMPs, tissue inhibitor of metalloproteinases (TIMPs) and growth factors in ameloblastoma. METHODS AND RESULTS: Thirteen cases of solid/multicystic ameloblastoma were examined. As a control, calcifying cystic odontogenic tumour (CCOT), a non-invasive odontogenic neoplasm with ameloblastomatous epithelium was also studied. Immunohistochemistry detected MMPs, TIMPs and growth factors in ameloblastoma and CCOT. The labelling index (LI) of MMP-9 and TIMP-2 was significantly higher in ameloblastoma compared with CCOT. The LI of epidermal growth factor (EGF), transforming growth factor (TGF)-alpha and epidermal growth factor receptor (EGFR) was also increased in ameloblastoma. This neoplasm showed greater expression of MMPs, TIMPs and growth factors compared with CCOT. We then analysed these molecules in ameloblastoma cells and stroma. Ameloblastoma cells exhibited increased LI of MMP-1, -2 and EGFR. We found a positive correlation between EGF and TIMP-1, and between TGF-alpha and TIMP-2. It is known that signals generated by growth factors are transduced by the ERK pathway. Ameloblastoma stroma exhibited the phosphorylated (activated) form of ERK. CONCLUSIONS: These results suggest an interplay involving growth factors MMPs and TIMPs that may contribute to ameloblastoma behaviour. Signals generated by this molecular network would be transduced by ERK 1/2 pathway.
Assuntos
Ameloblastoma/metabolismo , Ameloblastoma/patologia , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Neoplasias Maxilomandibulares/metabolismo , Neoplasias Maxilomandibulares/patologia , Metaloproteinases da Matriz/metabolismo , Inibidores Teciduais de Metaloproteinases/metabolismo , Proliferação de Células , Fator de Crescimento Epidérmico/metabolismo , Receptores ErbB/metabolismo , Humanos , Imuno-Histoquímica , Sistema de Sinalização das MAP Quinases , Metaloproteinase 1 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Cisto Odontogênico Calcificante/metabolismo , Cisto Odontogênico Calcificante/patologia , Células Estromais/metabolismo , Células Estromais/patologia , Inibidor Tecidual de Metaloproteinase-2/metabolismo , Fator de Crescimento Transformador alfa/metabolismoRESUMO
OBJECTIVE: The benign epithelial odontogenic tumours constitute a group of lesions derived from epithelial elements of the tooth-forming apparatus. This group includes lesions of different biological behaviour, such as ameloblastoma, calcifying cystic odontogenic tumour (CCOT) and adenomatoid odontogenic tumour (AOT). The pathogenesis of these neoplasms remains uncertain and the occurrence of methylation in cell-cycle related genes may be involved in their development. The aim of this study was to investigate the methylation status of P16, P21, P27, P53 and RB1 genes in epithelial odontogenic tumours. DESIGN: Methylation-specific polymerase chain reaction (MSP) was used to evaluate the presence of methylation in 13 samples of ameloblastoma, six samples of CCOT, three samples of AOT and 14 samples of dental follicles, included as control. RESULTS: Our results showed a distinct methylation profile in each group. In ameloblastoma, the highest methylated genes were P16 and P21, while in CCOT the P21 and RB1 genes were the most commonly methylated genes. Only the P16 and P21 genes were methylated in the AOT samples. In the dental follicle samples, P16, P27 and RB1 genes were commonly methylated. A high percentage of the odontogenic tumours analysed showed methylation of the P21 gene, in contrast to dental follicles. CONCLUSIONS: Epithelial odontogenic tumours show a distinct methylation profile in cell-cycle associated genes. In addition to this, the current findings show that epigenetic alterations are common events in epithelial odontogenic tumours.
Assuntos
Proteínas de Ciclo Celular/genética , Metilação de DNA/genética , DNA de Neoplasias/metabolismo , Proteínas de Neoplasias/genética , Tumores Odontogênicos/genética , Adenoma/genética , Adenoma/metabolismo , Ameloblastoma/genética , Ameloblastoma/metabolismo , Proteínas de Ciclo Celular/metabolismo , Saco Dentário/metabolismo , Células Epiteliais/metabolismo , Humanos , Proteínas de Neoplasias/metabolismo , Cisto Odontogênico Calcificante/genética , Cisto Odontogênico Calcificante/metabolismo , Tumores Odontogênicos/metabolismo , Reação em Cadeia da Polimerase/métodosRESUMO
Ameloblastomatous epithelium containing clusters of ghost cells is the typical histopathology of calcifying cystic odontogenic tumor (CCOT). This paper aimed to assess keratins AE1-AE3, K7, K10/13, K14, K18, K19, vimentin, laminin, and collagen IV in 08 CCOTs to discuss their histopathogenesis. Similarity to the immunoprofile of the stratified squamous epithelium was seen in the with the basal layer expressing K14 and the upper cells expressing K10/13. When compared to the immunoprofile of the normal odontogenic epithelium, of odontogenic tumor epithelia and of the ghost cells described in the literature, it was possible to suggest that the CCOT epithelium differentiates towards squamous type.
Assuntos
Neoplasias Maxilomandibulares/metabolismo , Neoplasias Maxilomandibulares/patologia , Queratinas/biossíntese , Cisto Odontogênico Calcificante/metabolismo , Cisto Odontogênico Calcificante/patologia , Diferenciação Celular , Transformação Celular Neoplásica , Colágeno Tipo IV/biossíntese , Epitélio/metabolismo , Humanos , Imuno-Histoquímica , Laminina/biossíntese , Vimentina/biossínteseRESUMO
Odontogenic tumors composed of two or more distinct types of lesions are unusual. In this paper, a case of an odontogenic lesion characterized by simultaneous occurrence of areas of calcifying odontogenic cyst (COC) and orthokeratinized odontogenic cyst (OOC) is described. The lesion was asymptomatic and presented at the radiographic examination as a unilocular well-delimited radiolucency extending from left incisor to right premolar area in the mandible. To date, this is the first report of COC associated with an OOC.