Imunoexpressão de clic4, α-sma, e-caderina e vimentina em lesões odontogênicas epitelias benígnas / Immunoexpression of clic4, α-sma, e-cadherin and vimentin in benign epithelial odontogenic lesions

As lesões odontogênicas epiteliais benignas constituem um grupo heterogêneo de lesões. A proteína CLIC4 atua na regulação dos processos de parada de crescimento e apoptose, participando também do processo de transdiferenciação dos fibroblastos em miofibroblastos que passam a expressar α-SMA. Além disso, a expressão de CLIC4 pode interferir no processo de transição epitélio-mesenquima (TEM) em neoplasias. Este trabalho avaliou a imunoexpressão de CLIC4, α-SMA, E-caderina e Vimentina em ameloblastomas (AM) (n = 16), ceratocistos odontogênicos (n = 20) e tumores odontogênicos adenomatóides (TOA) (n = 8). A análise da expressão imunoistoquímica das proteínas CLIC4, E-caderina e vimentina no componente epitelial das lesões e de CLIC4 e α-SMA no tecido conjuntivo foi realizada de forma semi-quantitativa por um avaliador previamente calibrado. A expressão no componente epitelial de CLIC4 foi analisada separadamente no núcleo e no citoplasma, bem como a marcação de E-caderina que foi avaliada na membrana e no citoplasma. As comparações dos percentuais de imunorreatividade em relação aos grupos estudados foram realizadas por meio dos testes não paramétricos de Kruskal-Wallis e Mann-Whitney. Possíveis correlações entre a expressão de CLIC4, α-SMA, E-caderina e Vimentina foram avaliadas por meio do teste de correlação de Spearman. O nível de significância foi estabelecido em 5% (p < 0,05). Foram observados diferentes padrões de marcação entre os grupos analisados, observando-se que a imunoexpressão exclusivamente citoplasmática da CLIC4 no componente epitelial dos AM (p < 0,001) e TOA (p < 0,001) foi significativamente superior a dos CO, não demonstrarando significância estatística entre os AM e TOA. A imunoexpressão (nuclear e citoplasmática) da CLIC4 no revestimento epitelial CO foi significativamente superior à encontrada no componente epitelial dos AM (p < 0,001) e dos TOA (p < 0,001). A imunoexpressão estromal de CLIC4 foi significativamente superior nos AM (p = 0,009) e CO (p = 0,004) quando comparados aos TOA. A imunoexpressao de α-SMA significativamente maior em AM (p = 0,016) e CO (p = 0,034) quando comparados aos TOA. Para a imunoexpressão membranar da E-caderina em CO foi significativamente superior em comparação à encontrada nos AM (p = 0,009) e nos TOA (p = 0,024). Foi observada maior imunoexpressão de E-caderina (membranar e citoplasmática) nos COs, quando comparados aos AM (p < 0,001) e aos TOAs (p < 0,001). A expressão de Ecaderina citoplasmática foi significativamente maior nos AM e TOA (p < 0,001) quando comparados aos CO. Observou-se diferença estatisticamente significativa na imunoexpressão de vimentina entre os casos de AM e os casos de TOA (p = 0,038) e CO (p < 0,001), bem como entre o TOA e CO (p < 0,001). As correlações testadas entre os escores das proteínas estudadas evidenciou que no grupo dos AM foi possível evidenciar moderada correlação positiva e estatisticamente significativa (r = 0,527; p = 0,036) entre a expressão citoplasmática da CLIC4 e a expressão citoplasmática da E-caderina. Também foi verificada fraca correlação negativa e estatisticamente significativa (r = -0,499; p = 0,049) entre a expressão núcleo-citoplasmática da CLIC4 e a expressão citoplasmática da E-caderina nos AM. Além disso, uma moderada correlação positiva e estatisticamente significativa entre a expressão estromal da CLIC4 e a expressão da α-SMA nos AM (r = 0,648; p = 0,007) e nos CO (r = 0,541; p = 0,014). Foi observada forte correlação negativa e estatisticamente significativa (r = -0,813; p < 0,001) entre a expressão da E-caderina e a expressão da vimentina nos AM. Os resultados deste estudo sugerem um potencial envolvimento de CLIC4 no processo de transdiferenciação de miofibroblastos, e que a presença destas células é mais frequentemente associada a lesões de comportamento biológico mais agressivo como os AM e CO, além de uma possível atuação desta proteína na regulação do ciclo celular e na TEM nas lesões estudadas (AU).

Benign epithelial odontogenic lesions constitute a heterogeneous group of lesions. the CLIC4 protein acts in the regulation of growth arrest and apoptosis processes, also participating in the process of transdifferentiation of fibroblasts Into myofibroblasts that begin to express α-SMA. Furthermore, CLIC4 expression can interfere with the epithelialmesenchymal transition (EMT) process in neoplasms. This work evaluated the immunoexpression of CLIC4, α-SMA, e-cadherin and vimentin in ameloblastomas (AM) (n = 16), odontogenic keratocysts (OK) (n = 20) and adenomatoid odontogenic tumors (AOT) (n = 8). The analysis of the immunohistochemical expression of the proteins CLIC4, ecadherin and vimentin in the epithelial component of the lesions and of CLIC4 and α-SMA in the connective tissue was carried out in a semi-quantitative way by a previously calibrated evaluator. Expression in the epithelial component of CLIC4 was analyzed separately in the nucleus and cytoplasm, as well as e-cadherin labeling, which was evaluated in the membrane and cytoplasm. Comparisons of the percentages of immunoreactivity in relation to the studied groups were carried out using the nonparametric kruskal-wallis and mann-whitney tests. Possible correlations between the expression of CLIC4, α-SMA, e-cadherin and vimentin were evaluated using the spearman correlation test. The significance level was set at 5% (p < 0.05). Different staining patterns were observed between the groups analyzed, observing that the exclusively cytoplasmic immunoexpression of CLIC4 in the epithelial component of AM (p < 0.001) and AOT (p < 0.001) was significantly higher than that of OK, not demonstrating statistical significance between the AM and AOT. The immunoexpression (nuclear and cytoplasmic) of CLIC4 in the co epithelial lining was significantly higher than that found in the epithelial component of AM (p < 0.001) and AOT (p < 0.001). Stromal CLIC4 immunoexpression was significantly higher in AM (p = 0.009) and OK (p = 0.004) when compared to AOT. The immunoexpression of α-SMA is significantly higher in AM (p = 0.016) and OK (p = 0.034) when compared to AOT. For e-cadherin membrane immunoexpression in co was significantly higher compared to that found in AM (p = 0.009) and AOT (p = 0.024). Greater immunoexpression of e-cadherin (membrane and cytoplasmic) was observed in OK, when compared to AM (p < 0.001) and AOT (p < 0.001). Cytoplasmic ecadherin expression was significantly higher in AM and AOT (p < 0.001) when compared to OK. A statistically significant difference in vimentin immunoexpression was observed between cases of AM and cases of AOT (p = 0.038) and OK (p < 0.001), as well as between AOT and OK (p < 0.001). The correlations tested between the scores of the proteins studied showed that in the am group it was possible to demonstrate a moderate positive and statistically significant correlation (r = 0.527; p = 0.036) between the cytoplasmic expression of clic4 and the cytoplasmic expression of e-cadherin. A weak and statistically significant negative correlation (r = -0.499; p = 0.049) was also found between the nucleus-cytoplasmic expression of clic4 and the cytoplasmic expression of e- cadherin in AM. Furthermore, a moderate positive and statistically significant correlation between the stromal expression of CLIC4 and the expression of α-SMA in AM (r = 0.648; p = 0.007) and OK (r = 0.541; p = 0.014). Additionally, a strong negative and statistically significant correlation (r = -0.813; p < 0.001) was observed between the expression of ecadherin and the expression of vimentin in AM. The results of this study suggest a potential involvement of CLIC4 in the myofibroblast transdifferentiation process, and that the presence of these cells is more frequently associated with lesions with more aggressive biological behavior such as AM and OK, in addition to a possible role of this protein in the regulation of cell cycle and EMT in the lesions studied (AU).

Variability in the Epithelial Expression of Ki67 and Polarization Characteristics of Collagen in Odontogenic Cysts and Tumours

ABSTRACT Objective: To assess the proliferation of epithelium (using the Ki67 index) and the polarization pattern of collagen in selected odontogenic cysts and tumours. In addition, an exploratory analysis of the effect of inflammation on the proliferation rate was done. Material and Methods: Following immunohistochemical staining, the labelling/proliferation index of Ki67 was calculated. The thickness and corresponding polarization colour of 100 juxta-epithelial picrosirius red-stained collagen fibers were assessed using linear micrometry with an eyepiece reticule under × 1000 magnification. Inflammation was graded subjectively as mild, moderate, and severe. Results: Overall Ki-67 expression was higher in the radicular cyst, Odontogenic Keratocyst, Ameloblastoma, while suprabasal Ki-67 positivity was maximum in Odontogenic Keratocyst. The stromal collagen fibers in Ameloblastoma showed predominantly green birefringence, whereas Odontogenic Keratocyst had orange birefringence. There was no significant association of inflammation with Ki-67 expression or birefringence patterns. Conclusion: The highest Ki67 expression in the radicular cyst, followed by Odontogenic Keratocyst and Ameloblastoma. Differences in the collagen maturation pattern were noted innately in five lesions studied and were further influenced by inflammatory changes. Epithelial proliferation and concomitant expression of thickness and maturity of the stromal collagen are innate features of the lesion further influenced by inflammation in various odontogenic cysts and tumours and may, in turn, guide the clinical behavior.

Recorrência do ameloblastoma: análise de fatores clínicoradiográficos e imunoexpressão de hMSH2, hMLH1 e KI-67 / Ameloblastoma recurrence: analysis of clinical-radiographic factors and immunoexpression of hMSH2, hMLH1 and KI-67

Introdução: O ameloblastoma é uma neoplasia odontogênica benigna, que apresenta altas taxas de recorrência pós-operatória. Diversos estudos mostram a relação entre as características clínico-patológicas e as modalidades de tratamento na recorrência do ameloblastoma. Os mecanismos moleculares envolvidos com a etiopatogenia deste tumor são pouco conhecidos, e apesar de alterações no Sistema Mismatch favorecerem o desenvolvimento de diferentes neoplasias humanas, a importância destes no desenvolvimento do ameloblastoma ainda permanece pouco compreendido. Objetivo: Identificar os fatores clínico-patológicos associados à recorrência do ameloblastoma, bem como investigar o papel da imunoexpressão das proteínas hMLH1, hMSH2 e Ki-67 na recidiva desses tumores odontogênicos. Metodologia: Tratou-se de um estudo descritivo, transversal e restrospectivo, com uma amostra constituída por 22 casos de ameloblastomas recidivantes e 22 casos não-recidivantes. A análise imunoistoquímica foi realizada de forma quantitativa, considerando a localização celular (nuclear) das proteínas estudadas. O teste de McNemar foi utilizado para comparar as variáveis entre lesões da 1ª biópsia e recorrentes de AMB. A sobrevida livre de recorrência foi analisada pelo método de Kaplan-Meier e as funções de sobrevida foram comparadas de acordo com as variáveis pelo teste log-rank. Resultados: O gênero mais acometido foi o feminino (n=24; 54,5%), com média de idade de acometimento de 39,1 ± 19,8 anos, sendo 45,5% (n=20) leucodermas. A região posterior de mandíbula foi a mais frequente no grupo recidivante (n=18, 81,8%) e também para os casos que não apresentaram recidivas (n=16, 72,8%). O tempo livre de recorrência foi de 50,0 (34,5 ­ 63,6) meses. Foram fatores significativamente associadas à recorrência dos ameloblastomas: presença de expansão da cortical (p=0,0089), ausência de reconstrução óssea (p=0,018), tratamento conservador (p=0,021), perda de imunoexpressão de hMSH2 (p=0,006) e hMLH1 (p=0,038) e forte imunoexpressão de Ki-67 (p=0,029). Conclusão: Baseado nos achados desta pesquisa, aspecto radiográfico, modalidade do tratamento e imunoexpressão de proteínas do Sistema Mismatch e Ki-67 podem ser utilizados como indicadores para a recorrência em ameloblastomas (AU).

Introduction: Ameloblastoma is a benign odontogenic neoplasm, which has high rates of postoperative recurrence. Several studies show the relationship between clinicopathological characteristics and treatment modalities in ameloblastoma recurrence. The molecular mechanisms involved in the etiopathogenesis of this tumor are little known, and although changes in the Mismatch System favor the development of different human neoplasms, their importance in the development of ameloblastoma still remains poorly understood. Objective: To identify clinical and pathological factors associated with ameloblastoma recurrence, as well as to investigate the role of immunoexpression of hMLH1, hMSH2 and Ki-67 proteins in the recurrence of these odontogenic tumors. Methodology: This was a descriptive, cross-sectional and retrospective study, with a sample consisting of 22 cases of recurrent ameloblastoma and 22 non-recurrent cases. Immunohistochemical analysis was performed quantitatively, considering the cellular (nuclear) location of the studied proteins. McNemar's test was used to compare variables between 1st biopsy and recurrent AMB lesions. Recurrence-free survival was analyzed using the Kaplan-Meier method and survival functions were compared according to variables using the log-rank test. Results: The most affected gender was female (n=24; 54.5%), with a mean age of involvement of 39.1 ± 19.8 years, 45.5% (n=20) being white. The posterior region of the mandible was the most frequent in the relapsed group (n=18, 81.8%) and also for the cases that did not present recurrences (n=16, 72.8%). Recurrence-free time was 50.0 (34.5 ­ 63.6) months. Factors significantly associated with recurrence of AMBs were: presence of cortical expansion (p=0.0089), absence of bone reconstruction (p=0.018), conservative treatment (p=0.021), loss of hMSH2 immunoexpression (p=0.006) and hMLH1 (p=0.038) and strong Ki-67 immunoexpression (p=0.029). Conclusion: Based on the findings of this research, radiographic appearance, treatment modality and immunoexpression of proteins from the Mismatch System and Ki-67 can be used as indicators for recurrence in ameloblastomas (AU).

Identification of BRAF V600E mutation in odontogenic tumors by high-performance MALDI-TOF analysis / 国际口腔科学杂志·英文版

Odontogenic tumors are rare lesions with unknown etiopathogenesis. Most of them are benign, but local aggressiveness, infiltrative potential, and high recurrence rate characterize some entities. The MAP-kinase pathway activation can represent a primary critical event in odontogenic tumorigenesis. Especially, the BRAF V600E mutation has been involved in 80-90% of ameloblastic lesions, offering a biological rationale for developing new targeted therapies. The study aims to evaluate the BRAF V600E mutation in odontogenic lesions, comparing three different detection methods and focusing on the Sequenom MassARRAY System. 81 surgical samples of odontogenic lesions were subjected to immunohistochemical analysis, Sanger Sequencing, and Matrix-Assisted Laser Desorption/Ionization-Time of Flight mass spectrometry (Sequenom). The BRAF V600E mutation was revealed only in ameloblastoma samples. Moreover, the presence of BRAF V600E was significantly associated with the mandibular site (ρ = 0.627; P value <0.001) and the unicystic histotype (ρ = 0.299, P value <0.001). However, any significant difference of 10-years disease-free survival time was not revealed. Finally, Sequenom showed to be a 100% sensitive and 98.1% specific, suggesting its high-performance diagnostic accuracy. These results suggest the MAP-kinase pathway could contribute to ameloblastic tumorigenesis. Moreover, they could indicate the anatomical specificity of the driving mutations of mandibular ameloblastomas, providing a biological rational for developing new targeted therapies. Finally, the high diagnostic accuracy of Sequenom was confirmed.

Ameloblastoma cell lines derived from different subtypes demonstrate distinct developmental patterns in a novel animal experimental model

Abstract Objective Ameloblastoma is a representative odontogenic tumor comprising several characteristic invasive forms, and its pathophysiology has not been sufficiently elucidated. A stable animal experimental model using immortalized cell lines is crucial to explain the factors causing differences among the subtypes of ameloblastoma, but this model has not yet been disclosed. In this study, a novel animal experimental model has been established, using immortalized human ameloblastoma-derived cell lines. Methodology Ameloblastoma cells suspended in Matrigel were subcutaneously transplanted into the heads of immunodeficient mice. Two immortalized human ameloblastoma cell lines were used: AM-1 cells derived from the plexiform type and AM-3 cells derived from the follicular type. The tissues were evaluated histologically 30, 60, and 90 days after transplantation. Results Tumor masses formed in all transplanted mice. In addition, the tumors formed in each group transplanted with different ameloblastoma cells were histologically distinct: the tumors in the group transplanted with AM-1 cells were similar to the plexiform type, and those in the group transplanted with AM-3-cells were similar to the follicular type. Conclusions A novel, stable animal experimental model of ameloblastoma was established using two cell lines derived from different subtypes of the tumor. This model can help clarify its pathophysiology and hasten the development of new ameloblastoma treatment strategies.

Ameloblastoma e suas características clínicas e radiográficas: relato de caso clínico / Ameloblastoma and its clinical and radiographic characteristics: clinical case report

O ameloblastoma é um tumor odontogênico benigno raro que afeta a região mandibular. Possui um crescimento localizado, também pode ser infiltrativo e persistente, assintomático, com estímulo desencadeador desconhecido. Sua prevalência ocorre com maior frequência em pacientes entre a quarta e quinta década de vida. Além de ser um relato de caso clínico, o presente estudo visa esclarecer as características clínicas, radiográficas, histopatológicas, condutas e opções durante o tratamento e o prognóstico para os diversos tipos de ameloblastomas, sendo realizada a radiografia panorâmica, a tomografia computadorizada e exame histopatológico, obtendo o diagnóstico da variante unicística que possui as características como uma cavidade monocítica bem definida e radiograficamente apresenta radiolucências expansivas uniloculares com margens bem definidas. O tratamento inicial proposto foi a marsupialização, remoção à marsupialização na qual uma janela cirúrgica comunicando com a cavidade bucal, suturada junto à mucosa adjacente, é aberta para o esvaziamento progressivo do conteúdo interno da lesão, acarretando em sua descompressão, consequente diminuição. Após a reavaliação do caso foi observada a necessidade de remover toda a lesão, realizando a ressecção parcial da mandíbula com um melhor prognóstico(AU)

Ameloblastoma is a rare benign odontogenic tumor that affects the mandibular region, has a localized growth, may also be infiltrative and persistent, asymptomatic, with unknown triggering stimulus. Its prevalence occurs more frequently in patients between the fourth and fifth decade of life. In addition to being a clinical case report, the present study aims to clarify the clinical, radiographic, histopathological, behavioral and options characteristics during the treatment and the prognosis for the various types of ameloblastomas. Panoramic radiography, computed tomography and histopathological examination obtaining the diagnosis of the unicystic variant that has the characteristics as a well defined monocytic cav ity and radiographically presents expansive unilocular radiolucencies with well defined margins. The initial proposed treatment was the marsupialization removal to marsupialization in which a surgical window communicates with the oral cavity, sutured adjacent to the adjacent mucosa, is opened for progressive emptying of the internal contents of the lesion, leading to its decompression and consequent decrease. After the reassessment of the case, it was observed the need to remove the entire lesion, performing partial resection of the mandible with a better prognosis(AU)

Ameloblastoma unicístico: relato de caso / Unicystic ameloblastoma: case report

Objetivo: relatar um caso de ameloblastoma unicístico, com intuito de descrever os seus aspectos clínicos, radiográficos e histopatológicos e a abordagem terapêutica, bem como discutir com base na literatura. Relato de caso: paciente do sexo feminino, 14 anos, procurou a clínica-escola do Curso de Odontologia da Universidade Estadual de Feira de Santana, acompanhada de sua genitora, referindo como queixa principal: "meu queixo tá inchado". No exame físico intrabucal, observou-se tumefação em região mandibular esquerda, circunscrita estendendo-se do dente 31 ao 35, com consistência endurecida a palpação e ausência do dente 33. Foi realizada uma descompressão cirúrgica e biópsia incisional. O diagnóstico histopatológico confirmou a presença de infiltração mural por epitélio ameloblástico. Após confirmado o diagnóstico de ameloblastoma unicístico do tipo mural, o tratamento de escolha foi enucleação e curetagem da lesão. Considerações finais: esse tumor, quando tratado de forma conservadora, apresenta prognóstico favorável. Técnicas alternativas cada vez mais conservadoras estão sendo utilizadas no seu tratamento. Ainda assim, é importante o acompanhamento clínico e radiográfico de longo prazo, devido ao risco de recorrência após longos períodos. (AU)

Objective: this study aimed to report a case of unicystic ameloblastoma to describe its clinical, radiographic, histopathological, and therapeutic aspects, as well as to discuss the literature. Case report: a 14-year-old female patient attended the clinic of the School of Dentistry of Feira de Santana State University, accompanied by her mother, with the main complaint of a swollen chin. The intraoral physical examination revealed tumefaction in the left mandibular region, circumscribed, extending from tooth 31 to 35, hard on palpation, and absence of tooth 33. A surgical decompression and incisional biopsy were performed, and the histopathological diagnosis confirmed the presence of mural infiltration by ameloblastic epithelium. After confirming the diagnosis of mural unicystic ameloblastoma, the treatment of choice was enucleation and curettage of the lesion. Final considerations: this tumor, when treated conservatively, presents a favorable prognosis. Increasingly conservative techniques are being used as alternative treatments of this condition. Nevertheless, long-term clinical and radiographic monitoring is important because of the risk of recurrence after long periods. (AU)

Malignant ameloblastoma: a challenging diagnosis

Ameloblastoma is an uncommon and locally aggressive, benign, odontogenic tumor, with local recurrence when not adequately excised. A rare variant of this neoplasm with the benign features but accompanied with metastases has been described. This rare variant is malignant ameloblastoma and is known to have a poor prognosis. We present the case of a young woman who had recurrent mandibular tumors, which were resected twice and histologically reported as ameloblastoma. Four years later, she presented with pulmonary metastasis and atelectasis. A review of the literature on this very rare neoplasm was also performed.

Ameloblastoma with distinctive granular cell pattern: an 8 case study

Ameloblastoma with granular cell pattern (AGC) is classified as an unusual histological subtype of solid/multicystic ameloblastoma, characterized by granular changes in stellate-like cells located within the inner portion of the epithelial follicles. Studies have revealed that lysosomal overload causes cytoplasmic granularity; however, the mechanism involved remains poorly understood. Here we report on eight cases of granular cell ameloblastoma, in the posterior region of the mandible. The age of the patients included in this case series ranged from 35 -64 years old and 87.5% of cases occurred in non-Caucasians, with a slight gender predilection for men (62.5%). There was no evidence of recurrence, and the majority of the cases were treated with surgical resection (87.5%). All tumors displayed histopathological features consistent with the diagnosis of ameloblastoma with granular cell pattern.

Estudo da expressão imunohistoquímica de SO2, FGF-10 e WNT-1 em lesões odontogênicas epiteliais benignas / Study of the immunohistochemical expression of SO2, FGF-10 and WNT-1 in benign epithelial odontogenic lesions

Os dentes desenvolvem-se a partir de interações sequenciais entre o epitélio e o mesênquima derivado da crista neural em diferentes estágios de histodiferenciação e morfodiferenciação. Ao final da odontogênese, espera-se que as estruturas que participaram da formação destes tecidos desapareçam ou permaneçam quiescentes. Não é incomum que os remanescentes epiteliais da odontogênese originem lesões, como cistos e tumores odontogênicos. No desenvolvimento dentário precoce, a manutenção das células-tronco é regulada por uma série de fatores de transcrição específicos, que inclui OCT-4, SOX-2, Nanog, Stat-3 e c-Myc e diversos outros genes Homeobox e vias de transcrição (SHH, Wnt/ß-catenina, FGF, BMP) contribuem para o destino e diferenciação celular. No entanto, há a participação destes genes e vias na patogênese de vários tipos de tumores. O objetivo do presente estudo foi avaliar a imunoexpressão de SOX2, FGF-10 e Wnt-1 em uma série de casos de lesões odontogênicas e alguns espécimes de germes dentários. A amostra consistiu de 20 Ceratocistos Odontogênicos (CO), 20 Ameloblastomas sólidos (AM), 20 Tumores odontogênicos adenomatoides (TOA), 10 Tumores odontogênico epitelial calcificante (TOEC) e 05 casos de germes dentários usados comparativamente. A imunoexpressão foi avaliada de acordo com o percentual de células epiteliais imunomarcadas e intensidade de células positivas resultando na pontuação de imunomarcação total (PIT) que variou de 0 a 7. A análise da imunoexpressão da SOX2 revelou positividade na maioria dos casos das lesões estudadas. A pontuação de imunomarcação para SOX2 revelou haver diferença estatisticamente significativa entre os grupos de lesões estudadas, com maior frequência em CO e TOEC (p <0,001). Após o pareamento, observou-se diferença significativa entre AM e CO, AM e TOEC, CO e TOA, CO e TOEC e, TOA e TOEC (p <0,05). A análise da imunoexpressão da FGF-10 e Wnt-1 revelou positividade em todos os casos das lesões estudadas, mas sem diferença estatisticamente significativa entre os grupos de lesões estudadas (p = 0,628). Houve diferença significativa em relação aos escores de positividade para Wnt-1 (p <0,001) com maior frequência em CO e TOA. Após o pareamento, observou-se existir diferença estatisticamente significativa entre AM e CO, AM e TOEC, CO e TOEC e, TOA e TOEC (p <0,05). O padrão de expressão de SOX2, FGF-10 e Wnt-1, em germes dentários e nas lesões odontogênicas aqui avaliadas, confirma a participação destas vias na odontogênese e também no desenvolvimento das lesões odontogênicas (AU).

Dental development occurs from sequential interactions between the epithelium and the mesenchyme derived from the neural crest at different stages of histodifferentiation and morphodifferentiation. At the end of tooth development, the structures that participated in the formation of these tissues are expected to disappear or remain quiescent. It is not uncommon that the epithelial remnants of the tooth development originate lesions such as odontogenic cysts and tumors. In early tooth development, stem cell maintenance is regulated by specific transcription factors, which includes OCT-4, SOX-2, Nanog, Stat-3 and c-Myc and several other Homeobox genes and transcription pathways (SHH, Wnt/ß-catenin, FGF, BMP) contribute to cell fate and differentiation. However, there is involvement of these genes and pathways in the pathogenesis of several types of tumors. The aim of the present study was to evaluate the immunoexpression of SOX2, FGF-10 and Wnt-1 in a case series of odontogenic lesions and some specimens of dental germs. The sample consisted of 20 Odontogenic Keratocysts (OK), 20 solid ameloblastomas (AM), 20 adenomatoid odontogenic tumors (AOT), 10 calcifying epithelial odontogenic tumors (CEOT) and 5 dental gerns for comparison. Immunoexpression was evaluated according to the percentage of immunostained epithelial cells and intensity of the positive cells resulting in total immunostaining score (PIT) ranging from 0 to 7. The analysis of SOX2 immunoexpression revealed positivity in most cases of the lesions studied. The immunostaining score for SOX2 revealed a statistically significant difference between the groups of lesions studied, with a higher frequency in OK and CEOT (p < 0.001). After pairing, we observed a significant difference between AM and OK, AM and CEOT, OK and AOT, OK and CEOT, and AOT and CEOT (p <0.05). Analysis of the FGF-10 and Wnt-1 immunoexpression revealed positivity in all cases of the lesions studied, with no statistically significant difference between the groups of lesions studied (p = 0.628). There was a significant difference in relation to the positivity scores for Wnt-1 (p <0.001) with higher frequency in OK and AOT. After pairing, there was a statistically significant difference between AM and OK, AM and CEOT, OK and CEOT and, AOT and CEOT (p <0.05). The expression pattern of SOX2, FGF-10 and Wnt-1 in dental germs and odontogenic lesions evaluated here confirms the participation of these pathways in the tooth development as well as in the development of odontogenic lesions (AU).

Ameloblastoma maxilar superior: presentación de caso clínico / Upper maxillary ameloblastoma: report of a clinical case

El ameloblastoma es una entidad patológica benigna de origen odontogénico, de alta agresividad local, lo que ha sido un punto de controversia en la literatura científica. Se presenta un caso clínico, con ubicación en maxilar superior con diagnóstico de ameloblastoma sólido multiquístico. Se evalúa el caso, su posibilidad de tratamiento, revisando las características clínicas y anatomopatológicas de laentidad, basándose en una búsqueda bibliográfica.

Ameloblastoma is a benign pathological entity of odontogenic origin, very aggressive at a local level, which has become a controversial issuein cientific literature. A clinic case is presented, located in the superior maxilla diagnosed as a solid multicystic ameloblastoma. The case isevaluated, its ways of treatment, the clinical and anatomopathological characteristics of the entity with an intensive bibliographical researc.

Epithelial odontogenic tumors: analysis of 156 cases in a Brazilian population / Tumores odontogénicos epiteliales: análisis de 156 casos en una población brasileña

The objective of this study was to determine the distribution of epithelial odontogenic tumors diagnosed histologically in a period of 41 years in a Brazilian population according to age, gender, site affected and compare these data with previously reported studies from other countries. Data of epithelial odontogenic tumors diagnosed were collected from the files of the Oral Pathology Laboratory of Federal University of Rio Grande do Norte, Natal, RN, Brazil, and entered in a standardized form for later comparisons. Clini-cal features obtained from the patient records and microscope slides were reviewed according to the 1992 World Health Organization classification. A total 156 epithelial odontogenic tumor were reported. Of these, all of them were benign. Ameloblastoma was the most frequent type (85.9 %), followed by adenomatoid odontogenic tumor (10.9 %) and calcifying epithelial odontogenic tumor (3.2 %). The mean age of the patients was 38 years, with a wide range (11­80 years). The posterior region of mandible was the anatomic site most frequently affected by this disease, and no significant differences were found between sexes in the diagnosis of odontogenic tumors. A marked geographic variation in the relative incidences of various epithelial odontogenic tumors was found. It was particularly notable in ameloblastomas and adenomatoid odontogenic tumors, with the incidences observed in the present study being similar, sometimes different to earlier studies in others parts of the world.

El objetivo fue determinar la distribución de los tumores odontogénicos epiteliales diagnosticados histológicamente en un período de 41 años en una población brasileña según edad, sexo y la zona afectada y comparar estos datos con estudios anteriores de otros países. Los datos de los tumores odontogénicos epiteliales diagnosticados fueron obtenidos de los archivos del Laboratorio de Patología Oral de la Universidad Federal de Rio Grande do Norte, Natal, RN, Brasil, e introducidos en un formulario estandarizado para comparaciones futuras. Las características clínicas obtenidas a partir de los registros de los pacientes y los portaobjetos de microscopio fueron revisados de acuerdo a la clasificación de la Organización Mundial de la Salud 1992. Se informó de un total de 156 tumores epiteliales odontogénicas. De estos, todos eran benignos. Ameloblastoma fue el tipo más frecuente (85,9 %), seguido por el tumor odontogénico adenomatoide (10,9 %) y el tumor odontogénico epitelial calcificante (3,2 %). La edad media de los pacientes fue de 38 años, con un rango amplio (11­80 años). La región posterior de la mandíbula era el sitio anatómico más afectado por esta enfermedad, y no se encontraron diferencias significativas entre sexos en el diagnóstico de los tumores odontogénicos. Se encontró una marcada variación geográfica en las incidencias relativas de diversos tumores odontogénicos epiteliales. Fue particularmente notable en ameloblastomas y tumores odontogénicos adenomatoide, con las incidencias observadas en este estudio siendo a veces similares, y a veces diferentes de los estudios anteriores en otras partes del mundo.

Expression of CD90 and P75NTR stem cell markers in ameloblastomas: a possible role in their biological behavior

Abstract Multicystic and unicystic ameloblastomas are benign odontogenic tumors that present distinct biological behavior. The investigation of stem cells has become an important branch of tumor biology, with several studies addressing the possible role of these cells in tumor growth, angiogenesis, progression, infiltration and invasiveness. This study evaluated the immunohistochemical expression of CD90(Thy-1) and P75NTR stem cell markers in multicystic and unicystic ameloblastomas. Seventeen (17) samples of ameloblastomas (multicystic, n = 10; unicystic, n = 7) were submitted to immunohistochemical reactions and graded semi-quantitatively. The Kolmogorov-Smirnov test was used to verify possible differences in CD90 and P75NTR expressions between multicystic and unicystic ameloblastomas (p < 0.05). CD90 immunostaining was observed in all multicystic ameloblastoma specimens (n = 10), in the cytoplasm of the fibroblasts and vascular endothelial cells of the tumor stroma, near the neoplastic odontogenic epithelia. The staining of stromal CD90 was significantly higher in multicystic than in unicystic ameloblastomas (p = 0.003). Nuclear P75NTR immunostaining was observed in all ameloblastoma specimens. A significant difference was seen in the epithelial staining of P75NTR between multicystic and unicystic types (p = 0.007). The increased expression of CD90 and P75NTR found in multicystic ameloblastomas suggests a behavioral biological difference between multicystic and unicystic ameloblastomas, as well as a difference in ameloblastoma development.

Ameloblastoma uniquístico plexiforme: a propósito de un caso / Plexiform unicystic ameloblastoma: a propos of a case

El ameloblastoma es un tumor odontogénico benigno de origen epitelialcon estroma fi broso maduro sin ectomesénquima odontogénico, decomportamiento localmente agresivo e infi ltrante con alta capacidad de recidiva. Representa entre 11 y 13 por ciento de los tumores odontogénicosmandibulares y 1 por ciento de los tumores y quistes maxilomandibulares. El tratamiento debe orientarse de acuerdo con el potencial del tumor,las características del crecimiento según su variable clínica y el tipo histológico. Debe ser un tratamiento que asegure un mejor pronóstico para el paciente

The ameloblastoma is a benign odontogenic tumor of epithelial origin with mature fi brous stroma, without odontogenic ectomesenchyme. It exhibits locally aggressive and invasive behavior, with a high level of recurrence. Ameloblastomata account for between 11 and 13% of mandibular odontogenic tumors, and 1% of maxillo-mandibular tumors and cysts. Treatment should be guided by the potential of the tumor and its growth characteristics based on the clinical variable and histological type, the preferred treatment being that which ensures the best prognosis for the patient.

Adenomatoid Odontogenic Tumor: A Case Report.

Adenomatoid odontogenic tumor (AOT) is a very rare odontogenic tumor with an incidence of 1%. Overall it accounts for 9% of all odontogenic tumors. In most of the cases, AOT is misdiagnosed as an odontogenic cyst. Younger individuals are commonly affected and particularly in females. AOT is seen predominantly in the maxillary anterior region in association with an unerupted tooth. Permanent dentition is affected more than the deciduous dentition. Intraoral periapical radiographs play a major role in the diagnosis compared to orthopantomogram because of its increased contrast but for the better assessment of the extension of larger lesions orthopantomogram is must. AOT resembles benign odontogenic lesions like dentigerous cyst and tumors like ameloblastoma. The lesions are managed conservatively by surgical excision along with the removal of the affected tooth and have an excellent prognosis.With this background, we report an unusual case of AOT involving maxillary anterior region in 15-year-old male patient. The present article reviews the etiology, clinical features, histopathological features, and treatment modalities of AOT.

Intraluminal Plexiform Unicystic Ameloblastoma: A Report of a Rarity in an 8-year-old Boy.

Unicystic ameloblastoma (UA) is a variant of ameloblastoma and this entity is more common in second to third decade of life. It is very rare in children with <2.2% under the age of 10 years. Th is odontogenic tumor is most commonly encountered in the posterior mandible and is associated with an impacted tooth. Th e term plexiform UA refers to a pattern of epithelial proliferation that has been described in cystic lesions of the jaws. Here is a report of a rare case of intraluminal plexiform UA, in the right posterior mandible of an 8-year-old boy presented to our department.

Expresión inmunohistoquímica de ki-67 y p53 en tumor odontogénico queratoquístico en comparación con ameloblastoma multiquístico / Immunohistochemical expression of Ki-67 and p53 in odontogenic keratocysts in comparison with ameloblastomas

Introducción: Ha sido descrita la inmunodetección de p53 y Ki-67 en el tumor odontogénico queratoquístico (TOQ) y en ameloblastomas mutiquísticos (AM). Sin embargo, hay escasa y contradictoria evidencia respecto de la comparación de estos dos marcadores entre estas neoplasias. Su estudio podría contribuir a comprender las diferencias que presentan en su comportamiento clínico y ser un complemento discriminatorio al momento de definir tratamiento, pronóstico y recidiva. Objetivo: Comparar el recuento de inmunomarcación de p53 y Ki-67 en células epiteliales de TOQ y AM, presentes en el registro de biopsias del Instituto de Referencia de Patología Oral (IREPO), de la Facultad de Odontología de la Universidad de Chile entre los años 2000-2011. Metodología: Estudio observacional de corte transversal. Se estudiaron mediante inmunohistoquímica 8 casos de TOQ y 6 casos de AM con diagnóstico histopatológico según la clasificación de la OMS del 2005. Las muestras se encontraban en bloques de parafina, fijadas en formalina. Resultados: Los datos mostraron una distribución normal en cuanto al número de células positivas para ambos inmunomarcadores. No hubo diferencias estadísticamente significativas en la inmunomarcación de Ki-67 y p53 para TOQ y AM. Sin embargo, en ambas neoplasias, la inmunomarcación de p53 fue mayor respecto a Ki-67, con una diferencia estadísticamente significativa tanto en TOQ (p=0.0134) como en AM (p=0.0079). Conclusión: Los resultados sugieren que la inhibición de apoptosis predominó en ambos tumores por sobre la multiplicación celular. Estas diferencias podrían relacionarse con su potencial de crecimiento.

Introduction: p53 and Ki-67 immunodetection have been described in the keratocystic odontogenic tumor (TOQ) and multicystic ameloblastomas (AM). However, there is limited and contradictory evidence regarding the comparison of these two markers between these neoplasias. Their study could help to understand the differences that occur in their clinical behavior and be a complement when defining discriminatory treatment, prognosis and recurrence. Objective: To compare the immunomarking count of p53 and Ki-67 in epithelial cells in AM and TOQ present in the biopsies registered at the Oral Pathology Reference Institute (IREPO), Faculty of Dentistry, University of Chile from 2000 to 2011. Methods: Cross-sectional observational study. 8 cases of TOQ and 6 cases of AM with histopathological diagnosis according to the WHO classification of 2005 were studied using immunohistochemistry. The samples were formalin-fixed and paraffin-embedded. Results: The data showed a normal distribution in the number of positive cells for both immunomarkers. There were no statistically significant differences in the Immunohistochemical expression of Ki-67 and p53 of TOQ and AM. However in both tumors, the immunohistochemical expression of p53 was higher compared to Ki-67, with a statistically significant difference in TOQ (p=0.0134) and AM (p=0.0079). Conclusion: The results suggest that inhibition of apoptosis in both tumors predominated over cell multiplication. These differences may be related to their growth potential.

Treatment of odontogenic ameloblastomas and their long term follow up at tertiary centre

Fifty-two patients of ameloblastoma were operated with special emphasis on radiographic and histological appearance. The unicystic radiographico-histological [38] cases were managed conservatively with marsupialization followed by enucleation [Group A' 15 Patients] and enucleation with peripheral ostectomy [Group B' 23 Patients]. The radiographico-histological multicystic [solid] variety [Group C' 14 Patients] was treated aggressively by resection. In conservative treatment regimens Carnoy's solution was applied after enucleation of the tumour whereas, the patients of aggressive surgery were operated with minimum 5mm safety marginal clearance of the tumour. The recurrence rate with average four years follow up was 0.0% for resection, 13.33% for marsupialization followed by enucleation and 8.69% for enucleation with peripheral ostectomy. The results were encouraging for unicystic ameloblastoma treated patients [Group A' and B'], in best interest of jaw bone contour preservation