Avaliação imuno-histoquímica da BMP-2, BMP-4 e seus receptores (BMPRIA e BMPRII) em ameloblastomas e tumor odontogênico adenomatóide

BMPs are components superfamily ligands transformation growth fator-β (TGF-β) secreted into the extracellular environment, with mechanisms of intercellular communication through specific ligands and receptors in various target cells, being recognized for its influence in osteogenic induction, also play an important role in tissue homeostasis, cell proliferation, differentiation control , in addition to being present in the development of various malignancies. The aim of this study was to compare the immunohistochemical expression of BMP-2, BMP-4 and its receptors BMPRIA and BMPRII in cases of ameloblastoma and adenomatoid odontogenic tumor. The sample consisted of 20 cases of solid ameloblastoma (SA), 10 cases of ameloblastoma unicystic (UA) and 16 cases of adenomatoid odontogenic tumor (AOT). The expression of BMPs and their receptors was evaluated in the parenchyma and stroma of lesions, establishing the percentage of immunopositive cells (0 - negative; 1-1 % to 10 % of cells positive; 2 - 11% to 25% of positive cells; 3 - 26% to 50% of cells positive; 4 - 51% to 75 % of positive cells; 5 - more than 75% positive cells). Analysis of the expression of BMP-2 revealed no statistically significant differences in parenchymal (p = 0.925) and stromal component (p = 0.345) between the groups, as well as BMP-4 (p = 0.873 / p = 0.131). In the epithelial component, SA and AOT had a higher frequency of score 5. In turn, all cases of UA were classified as score 5. The analysis of the stromal component showed no statistically significant difference between groups with respect to median scores BMPRIA positivity (p = 0.768) and BMPRII (p = 0.779). In the epithelial component of SA and UA, no statistically significant correlations between imunoexpression proteins analyzed were observed. In turn, the group of AOT, statistically significant positive correlations between the scores of expression of all studied proteins were found. In the stromal component, statistically significant positive correlations were found only in the SA group in BMP -4 and BMPRII (r = 0.476; p = .034), in the UA in BMP-4 and BMPRIA (r = 0.709; p = 0.022). The results of this study suggest that the BMPs and their receptors are involved in the development process odontogenic tumors. BMP-4, in turn, besides being present in odontogenic tumors have the capacity to form mineralized material.

Estudo comparativo entre o tumor odontogênico adenomatóide e tumor odontogênico epitelial calcificante a partir da técnica histoquímica do AgNOR e da imunohistoquímica do PCNA, p 53 e Ki-67

Pós-graduação em Odontologia - FOA

Expressão imuno-histoquímica metaloproteinase -1, -2 e -9 em ameloblastoma sólido e tumor odontogênico adematóide

Ameloblastoma and adenomatoid odontogenic tumor are odontogenic tumors arising from the odontogenic epithelium with distinct clinical behavior. In attempt to comprehend the interaction between the odontogenic tumor cells and the extracellular matrix, the present work evaluated and compared the immunohistochemical expression of the matrix metalloproteinases-1 (MMP-1), -2 (MMP-2) and -9 (MMP-9) in 20 cases of ameloblastoma and 10 adenomatoid odontogenic tumor. MMP-1 exhibited exuberant expression in the parenchyma and in the stroma of both studied tumors, while the MMP-2 showed varied expression with about of 80% and 60% of the neoplastic cells exhibiting positivity in the ameloblastoma and adenomatoid odontogenic tumor, respectively. With relation to the MMP-2 expression by the mesenchymal cells, it was observed that 65% of the ameloblastoma and 80% of the adenomatoid odontogenic tumor were positive. The immunoreactivity of MMP-9 was detected in all studied cases, although its expression had occurred predominantely in less than 50% of the parenchyma cells of the ameloblastoma, while in about of 60% of the adenomatoid odontogenic tumor more than 50% of cells were positive. The mesenchymal cells were positive to MMP-9 in 65% of the ameloblastoma and in 80% of the adenomatoid odontogenic tumor, respectively. Statistically significant difference was observed to the MMP-1 expression with relation to MMP-2 and MMP-9 in the ameloblastoma (p < 0.001). It was not possible to perform statistical analysis to the cases of adenomatoid odontogenic tumor, however there was a tendency toward a differential expression of the MMP-1 with relation to other studied MMPs. These results suggest that MMP-1, - 2 and -9 are implicated in the growth and progression of both tumors analyzed as well as the more pronounced participation of the stroma in the ameloblastoma could together to be related to the higher clinical aggressiveness

Lesões primárias e recidivantes do tumor odontogênico queratocístico e cisto odontogênico ortoqueratinizado: casuística e análise histoquímica, imuno-histoquímica da proliferação celular e citoqueratinas

Pós-graduação em Odontologia - FOA

Análise imunohistoquímica da ADAMTS-1 e proteoglicanos no ameloblastoma e no tumor odontogênico cístico calcificante

O ameloblastoma e o tumor odontogênico cístico calcificante (TOCC) são tumores odontogênicos que tem origem do epitélio odontogênico, porém ainda não é conhecido o estímulo ou gatilho que leva à transformação neoplásica desses tumores. O comportamento biológico das lesões é distinto, pois o ameloblastoma é um tumor mais agressivo e com taxa de recorrência significativa. Já o TOCC é um tumor menos agressivo e raramente há recorrência e por esse motivo foi utilizado como controle no estudo. Portanto, a elucidação completa dos mecanismos pelos quais esses tumores odontogênicos apresentam tais comportamentos biológicos continua sendo um desafio para os pesquisadores. As c (A Disintegrin and Metalloproteinase with ThromboSpondin) são metaloendopeptidases que são dependentes de zinco em seu domínio catalítico. Essas enzimas possuem ampla atividade catalítica contra uma variedade de substratos como os proteoglicanos (agrecan, brevican e versican), que são proteínas presente na matriz extracelular (MEC). As ADAMTS exibem características estruturais que lhes conferem um grande potencial para exibir múltiplas funções. Exibem função crucial em vários processos como proliferação, adesão, invasão e sinalização celular. As alterações nessas enzimas estão presentes em diversos tumores, o que sugere que estas proteínas podem estar envolvidas no processo carcinogênico em diferentes caminhos. Especificamente a ADAMTS-1 tem sido correlacionada com a tumorigênese de algumas neoplasias como no câncer de mama, pulmão e pâncreas. Assim como a ADAMTS, agrecan, brevican e versican são expressos em vários tumores e a regulação alterada desses proteoglicanos pode contribuir para o desenvolvimento da carcinogênese. Neste trabalho foram estudadas ADAMTS-1, agrecan, brevican e versican no ameloblastoma e TOCC. Foram incluídos 20 casos de ameloblastoma e 6 casos de TOCC, utilizados como controle. A expressão de ADAMTS-1, agrecan, brevican e versican foi avaliada por imunohistoquímica e as áreas de marcação foram mensuradas e analisadas. Para análise de correlação entre as proteínas estudadas utilizou-se o teste de Spearman. Todas as amostras de ameloblastoma expressaram ADAMTS-1, agrecan, brevican e versican. Todas as amostras de TOCC também expressaram as mesmas proteínas, porém numa quantidade significativamente menor que no ameloblastoma. A diferença de expressão de ADAMTS-1 e brevican no epitélio do ameloblastoma e do TOCC foi significante estatisticamente (p<0,0105). Assim como a expressão de agrecan e versican, no epitélio do ameloblastoma e do TOCC, também foi estatisticamente significante (p<0,0067) e (p<0,0148), respectivamente. Não houve correlação entre as proteínas estudadas.

Tratamento cirúrgico de tumor odontogênico queratocístico: relato de caso

Introduction: The Keratocystic Odontogenic Tumor (KCOT) is a benign odontogenic tumor with an infiltrative and potentially aggressive behavior with high recurrence rates. The KCOT occurs more often in men than women, with a frequency of 2:1, being more frequent in the mandible with a predilection for the body and branch. Treatment of KCOT remains controversial. Treatment usually includes enucleation, marsupialization, peripheral ostectomy, curettage associated with Carnoy solution and resection. Objective: To report a case of a KCOT located in the mandible. Case report: male patient, 15 years, with a KCOT on the right side of the mandible treated by enucleation and peripheral ostectomy, with four years of preservation, with no signs of recurrence. Final Comments: The treatment by enucleation associated with peripheral ostectomy reduces the relapse rate, preserves anatomical structures and can avoid a second surgical procedure for reconstruction of bone defects generated in surgery en bloc resection.

Study on the origin and nature of the adenomatoid odontogenic tumor by immunohistochemistry

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Tumor odontogênico queratocístico e considerações diagnósticas

Keratocystic odontogenic tumor (KCOT is benign, featuring controversies in diagnosis and treatment. It occurs mainly in the region of the mandibular angle, which may or may not be related to a tooth and whose importance is due to its aggressive behavior and high recurrence rate. The causes of high rates of relapse observed in this lesion are dependent on factors such as age, location and size of lesion, gender, type of treatment and histological variant. The thin capsule and friable connective tissue of KCOT may favor the retention of epithelial debris responsible for the high proliferative capacity of this clinical entity. Due to the aggressiveness with its recurrence this paper aims to conduct a literature review addressing clinical and imaging aspects, composes the histopathological diagnosis of KCOT.

Tumor odontogênico queratocístico: considerações clínico-cirúrgico

Introduction: The tumor odontogenic keratocyst (toq) is a benign disorder, which is controversial in its diagnosis and treatment. It is characterized by a true neoplasms arising from remnants the dental lamina. It occurs predominantly in the angle mandible, which may or may not be related to a tooth and whose importance is due to its aggressive behavior and high recurrence rate. The causes of the high recurrence rates. The thin capsule and friable tissue may favor the toq retention of epithelial debris and, moreover, the presence of satellite cells in the lesion site is responsible for the increased proliferative capacity of clinical entity. Objective: To present the peculiarities toq inherent in using a clinical case of toq in mandible. Case report: TOQ in the jaw in patient, 16 years old male presenting important lesion radiographically radiolucent related to the impacted tooth. Final comments: In consideration of the high rate of recurrence chosen treatment proved effective and was not any evidence of recurrence.

Tumor odontogênico queratocístico: relato de caso

Introduction: The odontogenic keratocyst tumor (OKT) derived from dental lamina rests with particularities and specific histological features, with high rates of relapse and aggressive clinical behavior. Presents certain predilection for males, affecting the mandible of 60% to 80% of cases may be related to impacted tooth 25 to 45% of cases. Objective: To highlight the clinical, histopathological and imaging procedures of the OKT, as well as discuss the treatment of this injury. Case Report: To report a case of 10 years of age to look for the orthodontist to correct anterior open bite was observed in panoramic radiography radiolucent area in the region of the body of the mandible associated with pathological inclusion of the lower premolar. It was performed an incisional biopsy of the lesion and the histopathologic diagnosis was odontogenic keratocyst tumor. It was performed a CT scan to assess the extent of the injury and its relation to anatomic structures. How to conduct, we opted for the extraction of the deciduous molar and enucleation of the lesion, preserving the premolar included. The same goes on clinical and radiographic control 18 months, after removal of OKT obtaining the eruption of premolar that was involved in the injury. Final Comments: It is necessary to adopt protocols that include dental care knowledge of oral diagnosis, medical history and careful clinical evaluation without forgetting the need for histopathological confirmation.

Tumor odontogênico queratocístico: revisão de literatura

The odontogenic keratocyst is called keratocyst odontogenic tumor (TOQ), due to its features compatible with neoplasms, such as its high recurrence rate and mechanism of growth. Although its etiology has unknown, the origin seems to be connected with dental lamina remaining. This entity is generally benign, with slow progression, asymptomatic, and among the odontogenic tumors, its prevalence is high. It affects mainly males, with predilection for the posterior mandible, while in most cases associated with an impacted tooth. Radiographically, this lesion is unilocular. Histological features are stratified epithelial basal cells with hyperchromatic paraqueratinizado. Treatment ranges from conservative to radical interventions. As a result of the controversy as TOQ tumor entity, the present work is a literature review of current findings, emphasizing its intrinsic features to contribute to developments in the study of this new entity.

Tumor odontogênico de células granulares

Introduction: the granular cell odontogenic tumors are an uncommon neoplasm with benign clinical behavior. The lesion occurs over a wide age range with a typically predilection for the mandibular canine and molar regions. Aim: present a granular cell odontogenic tumor literature review. Conclusions: the tumor don’t present an aggressive biological behavior although recurrences can occur. The lesion is treated by conservative surgery with curettage and enucleation as election procedures.

Distintas manifestações do tumor odontogênico cístico calcificante

O tumor odontogênico cístico calcificante normalmente se manifesta como uma massa indolor, de crescimento lento, que acomete tanto a maxila como a mandíbula, tendo predileção pelo segmento anterior (área dos incisivos e caninos). Geralmente, ocorre em adultos jovens, na terceira a quarta década de vida, sem preferência por gênero. Imagens de tomografia computadorizada revelaram características importantes não detectadas na radiografia panorâmica, tais como fenestração, calcificação e estruturas dentiformes. A característica microscópica típica dessa lesão é a presença de células epiteliais aberrantes anucleadas, em quantidades variáveis, denominadas "células fantasmas". Também se pode encontrar dentina displásica e, ocasionalmente, os cistos estão associados a tecido dentário duro, semelhante ao odontoma. O tratamento do tumor odontogênico cístico calcificante incluiu simples enucleação e curetagem. O objetivo deste trabalho foi mostrar duas manifestações diferentes do tumor odontogênico cístico calcificante, em que a tomografia computadorizada, associada às características clínicas, foi ferramenta importante para o diagnóstico, o planejamento cirúrgico e o acompanhamento dos pacientes.

Estudo imuno-histoquímico da presença de miofibroblastos e da expressão do fator transformador de crescimento-beta1, interferon gama, metaloproteinase de matriz 13 e indutor de metaloproteinases de matriz em lesões odontogênicas epiteliais

Myofibroblasts are cells that exhibit a hybrid phenotype, sharing the morphological characteristics of fibroblasts and smooth muscle cells, which is acquired during a process called differentiation. These cells then start to express -SMA, a marker that can be used for their identification. Studies suggest that myofibroblasts are related to the aggressiveness of different tumors and that TGF-1 and IFN- play a role in myofibroblast differentiation, stimulating or inhibiting this differentiation, respectively. The objective of this study was to investigate the role of myofibroblasts in epithelial odontogenic tumors, correlating the presence of these cells with the aggressiveness of the tumor. Immunohistochemistry was used to evaluate the expression of TGF-1 and IFN- in myofibroblast differentiation, as well as the expression of MMP-13, which is activated by myofibroblasts, and of EMMPRIN (extracellular matrix metalloproteinase inducer) as a precursor of this MMP. The sample consisted of 20 solid ameloblastomas, 10 unicystic ameloblastomas, 20 odontogenic keratocysts, and 20 adenomatoid odontogenic tumors. For evaluation of myofibroblasts, anti- -SMA-immunoreactive cells were quantified in connective tissue close to the epithelium. Immunoexpression of TGF-1, IFN-, MMP-13 and EMMPRIN was evaluated in the epithelial and connective tissue components, attributing scores of 0 to 4. The results showed a higher concentration of myofibroblasts in solid ameloblastomas (mean of 30.55), followed by odontogenic keratocysts (22.50), unicystic ameloblastomas (20.80), and adenomatoid odontogenic tumors (19.15) (p=0.001). No significant correlation between TGF-1 and IFN- was observed during the process of myofibroblast differentiation. There was also no correlation between the quantity of myofibroblasts and MMP-13 expression. Significant correlations were found between MMP-13 and TGF-1 (r=0.087; p=0.011), between MMP- 13 and IFN- (r=0.348; p=0.003), as well as between EMMPRIN and MMP-13 (r=0.474; p<0.001) and between EMMPRIN and IFN- (r=0.393; p=0.001). The higher quantity of myofibroblasts observed in solid ameloblastomas, odontogenic keratocysts and unicystic ameloblastomas suggests that these cells are one of the factors responsible for the more aggressive biological behavior of these tumors, although the myofibroblast population was not correlated with TGF-1, IFN-, MMP-13 or EMMPRIN. The correlation between MMP- 13 and TGF-1 suggests that the latter induces the expression of this metalloproteinase. The present results also support the well-established role of EMMPRIN as an inducer of MMP-13. Furthermore, the relationship between EMMPRIN and IFN- and between MMP-13 and IFN- suggests synergism in the antifibrotic effect of these markers