Bioengineering the ameloblastoma tumour to study its effect on bone nodule formation.

Ameloblastoma is a benign, epithelial cancer of the jawbone, which causes bone resorption and disfigurement to patients affected. The interaction of ameloblastoma with its tumour stroma drives invasion and progression. We used stiff collagen matrices to engineer active bone forming stroma, to probe the interaction of ameloblastoma with its native tumour bone microenvironment. This bone-stroma was assessed by nano-CT, transmission electron microscopy (TEM), Raman spectroscopy and gene analysis. Furthermore, we investigated gene correlation between bone forming 3D bone stroma and ameloblastoma introduced 3D bone stroma. Ameloblastoma cells increased expression of MMP-2 and -9 and RANK temporally in 3D compared to 2D. Our 3D biomimetic model formed bone nodules of an average surface area of 0.1 mm2 and average height of 92.37 [Formula: see text] 7.96 µm over 21 days. We demonstrate a woven bone phenotype with distinct mineral and matrix components and increased expression of bone formation genes in our engineered bone. Introducing ameloblastoma to the bone stroma, completely inhibited bone formation, in a spatially specific manner. Multivariate gene analysis showed that ameloblastoma cells downregulate bone formation genes such as RUNX2. Through the development of a comprehensive bone stroma, we show that an ameloblastoma tumour mass prevents osteoblasts from forming new bone nodules and severely restricted the growth of existing bone nodules. We have identified potential pathways for this inhibition. More critically, we present novel findings on the interaction of stromal osteoblasts with ameloblastoma.

Cisto dentígero com transformação ameloblástica / Quiste dentígero con transformación ameloblástica / Dentigerous cyst with ameloblastic transformation

Introdução: O cisto dentígero se origina pela separação do folículo que fica ao redor da coroa de um dente incluso. É o tipo mais comum de cisto odontogênico do desenvolvimento. O seu crescimento é lento, assintomático, e pode atingir grandes dimensões. Objetivo: Relatar um caso clínico cirúrgico de cisto dentígero com transformação ameloblástica, localizado na mandíbula, de paciente, gênero feminino, melanoderma, 14 anos. Caso clínico: Ao exame radiográfico apresentou área radiolúcida unilocular com margem bem definida e esclerótica envolvendo a coroa das unidades 48 e 47. Foi realizada enucleação e curetagem da lesão com exodontia destas unidades sob anestesia local em ambulatório, e aplicada a crioterapia na loja óssea. Encaminhou-se o conteúdo da lesão para exame histopatológico e o diagnóstico de cisto dentígero com transformação ameloblástica foi fechado. Comentários principais: No momento a paciente encontra-se em acompanhamento pós-operatório de 3 anos com neoformação óssea e sem recidivas(AU)

Introducción: El quiste dentígero se origina por la separación del folículo que se queda alrededor de la corona de un diente no erupcionado. Es el tipo más común de quiste odontogénico de desarrollo. Su crecimiento es lento, asintomático y puede alcanzar grandes dimensiones. Objetivo: Reportar un caso quirúrgico de quiste dentígero con transformación ameloblástica. Presentación del caso: Paciente femenina de 14 años, de color de piel negra. La radiografía demostró una radiolucidez unilocular con márgenes bien definidos que envolvían la corona de los dientes 48 y 47. El tratamiento involucró una combinación de enucleación y curetaje de la lesión, exodoncia de los dientes y crioterapia para desvitalizar el hueso circundante. Se realizó el examen histopatológico, luego, se confirmó el diagnóstico de quiste dentígero con transformación ameloblástica. Conclusiones: Al momento de la redacción del reporte la paciente se encontraba en seguimiento posoperatorio de tres años con neoformación ósea y sin recidivas(AU)

Introduction: Dentigerous cysts are caused by the separation of the follicle remaining around the crown of unerupted teeth. They are the most common type of developmental odontogenic cyst. Their growth is slow and asymptomatic, and they may reach large dimensions. Objective: Report a surgical case of dentigerous cyst with ameloblastic transformation. Case presentation: A case is presented of a black female 14-year-old patient. Radiography revealed an area of unilocular radiolucency with well-defined margins enveloping the crowns of teeth 48 and 47. Treatment was a combination of enucleation and curettage of the lesion, exodontia of the teeth and cryotherapy to devitalize the surrounding bone. Eventual histopathological examination confirmed the diagnosis of dentigerous cyst with ameloblastic transformation. Conclusions: At the time when the report was written, the patient had been followed up for three years after surgery, showing bone neoformation and no recurrence of the lesion(AU)

Ameloblastomas Exhibit Stem Cell Potential, Possess Neurotrophic Properties, and Establish Connections with Trigeminal Neurons.

Ameloblastomas are locally invasive and aggressive odontogenic tumors treated via surgical resection, which results in facial deformity and significant morbidity. Few studies have addressed the cellular and molecular events of ameloblastoma onset and progression, thus hampering the development of non-invasive therapeutic approaches. Tumorigenesis is driven by a plethora of factors, among which innervation has been long neglected. Recent findings have shown that innervation directly promotes tumor progression. On this basis, we investigated the molecular characteristics and neurotrophic properties of human ameloblastomas. Our results showed that ameloblastomas express dental epithelial stem cell markers, as well as components of the Notch signaling pathway, indicating persistence of stemness. We demonstrated that ameloblastomas express classical stem cell markers, exhibit stem cell potential, and form spheres. These tumors express also molecules of the Notch signaling pathway, fundamental for stem cells and their fate. Additionally, we showed that ameloblastomas express the neurotrophic factors NGF and BDNF, as well as their receptors TRKA, TRKB, and P75/NGFR, which are responsible for their innervation by trigeminal axons in vivo. In vitro studies using microfluidic devices showed that ameloblastoma cells attract and form connections with these nerves. Innervation of ameloblastomas might play a key role in the onset of this malignancy and might represent a promising target for non-invasive pharmacological interventions.

Effect of technetium-99 conjugated with methylene diphosphonate (99 Tc-MDP) on OPG/RANKL/RANK system in vitro.

BACKGROUND: RANKL and RANK play an important role in jaw resorption during the development of the ameloblastomas. Therefore, the aim of this study was to explore the effect of 99 Tc-MDP on OPG/RANKL/RANK system on RAW264.7 and MC3T3-E1 cell lines in vitro and provide the theoretical basis for the clinical treatment of the jaw ameloblastoma. METHODS: Different concentrations of 99 Tc-MDP were used to treat RAW264.7 and MC3T3-E1 cell lines. The cell proliferative inhibition rate was analyzed by CCK-8. Cell apoptosis and cell cycle were detected by flow cytometry. Western blot was used to detect the expression of OPG, RANKL, and RANK. RESULTS: Treatment of RAW264.7 cell lines with different concentrations of 99 Tc-MDP had inhibitory effects and decreased the expression of RANK protein. The cell proliferation of 99 Tc-MDP on MC3T3-E1 cell lines was stronger at 48 hours than at 24 hours except for 100 µg/mL concentration group. Compared with the concentration of 0.01 µg/mL, the treatment of MC3T3-E1 cells with 100 µg/mL 99 Tc-MDP showed that the cell proliferative effect decreased at 24 hours and 48 hours (P < 0.05). After treatment with 0.01 µg/mL 99 Tc-MDP, the expression of OPG in MC3T3-E1 cells was significantly increased (P < 0.05). Compared with 0.01 µg/mL, the expression of RANKL was decreased after treatment with 100 µg/mL 99 Tc-MDP (P < 0.05). CONCLUSION: 99 Tc-MDP can induce apoptosis of RAW264.7 cells and inhibit the expression of RANK protein. The effect of 0.01 µg/mL of low concentration of 99 Tc-MDP can promote the proliferation of MC3T3-E1 cells and increase the expression of OPG and RANKL protein. 99 Tc-MDP may have adjuvant therapeutic effects on the treatment of jaw ameloblastoma.

Expression profile of polycomb group proteins in odontogenic keratocyst and ameloblastoma.

Polycomb group (PcG) proteins are repressive chromatin modifiers required for proliferation and development. PcG proteins form two large repressive complexes, namely, Polycomb Repressive Complex 1 and 2. These proteins have been shown to drive tumorigenesis by repressing cell-type specific sets of target genes. Using immunohistochemistry, we investigated the expression patterns of five human PcG proteins, including Bmi-1, Ring1b, Mel-18, Ezh2, and Suz12, in various cellular components of odontogenic keratocysts (OKCs), ameloblastomas and, pericoronal follicles (PFs). In OKCs, expression of PcG proteins were found in the majority of cases while the expression pattern was relatively different for each PcG proteins. All PcG proteins were strongly expressed in the basal cells while some proteins showed variable expression in the parabasal and luminal cell layer of OKCs. In ameloblastomas, almost all PcG proteins showed a similar expression pattern of moderate to strong staining in the peripheral ameloblast-like cells and metaplastic squamous cells. Some of the central stellate reticulum-like cells also showed positive reaction to most PcG proteins. In PFs, most PcG proteins were intensely expressed in odontogenic epithelium lining the follicles, except Mel-18 and Suz12. The present study provides the initial evidence regarding epigenetic involvement by PcG proteins in these odontogenic lesions. Although these proteins are known to be in the same repressive group proteins, differential expression patterns of these proteins in OKCs and ameloblastomas indicates that these proteins may play different roles in pathogenesis of these odontogenic lesions.

Potential involvement of chondroitin sulfate A in the pathogenesis of ameloblastoma.

Ameloblastoma is classified as a benign odontogenic tumor characterized by locally invasive behavior and high risk of recurrence. Here, we evaluate a potential role for glycosaminoglycan, a structural component of cell membranes and extracellular matrix, in ameloblstoma pathogenesis. We subjected formalin-fixed, paraffin-embedded tissue sections of 34 cases of ameloblastoma, 10 of odontogenic keratocyst, and 17 of dentigerous cyst to immunohistochemistry using monoclonal antibodies recognizing chondroitin sulfate A (CS-A), heparan sulfate (HS), and keratan sulfate (KS). Expression levels of CS-A in epithelial component and stroma of ameloblastoma were significantly higher than those in odontogenic keratocyst and dentigerous cyst. Moreover, CS-A in ameloblastoma was more strongly expressed in stellate reticulum-like cells than in amelobast-like cells with statistical significance. On the other hand, expression levels of HS and KS in epithelial component and stroma of ameloblastoma were lower compared with CS-A. These results overall reveal that among these odontogenic lesions, CS-A is preferentially expessed in ameloblastoma, suggesting potential pathogenetic role probably in cytodifferention of tumor cells to stellate reticulum-like cells.

Les améloblastomes des maxillaires au centre hopsitalier universitaire d'odontosmatologie de Bamako

Introduction: L'objectif de cette étude était, d'évaluer les aspects sociodémographiques, cliniques, anatomopathologiques et thérapeutiques, des patients présentant des améloblastomes des maxillaires, au Centre Hospitalier Universitaire d'Odonto Stomatologie (CHU OS) de Bamako. Matériels et Méthode : Nous avons réalisé une étude rétrospective et prospective sur une période de trois ans (de Janvier 2007 à Décembre 2010), sur des cas d'améloblastomes des maxillaires, confirmés par un examen clinique, associé ou à la radiologie, ou à l'anatomopathologie. Les données ont été recueillies à partir des dossiers médicaux, saisies et analysées avec le logiciel Epiinfo. Résultats : Les lésions tumorales ont concerné 55 hommes et 43 femmes avec un sex-ratio de 1,27. Les femmes au foyer ont été les plus représentées soit 35,7% des cas. La radiographie des maxillaires a été effectuée chez 96% des patients et la biopsie dans 66,3% des cas. La localisation anatomique la plus fréquente a été mandibulaire dans 89,80% des cas, et la zone de prédilection a été la symphyse mandibulaire dans 34,7% des cas. La chirurgie conservatrice a été réalisée chez 50% des patients et la chirurgie radicale dans 26,5% des cas. Conclusion : Cette étude montre une fréquence élevée de l'améloblastome des maxillaires, et un intérêt capital pour une prise en charge précoce, dans un souci de minimiser les récidives

Recurrent giant mandibular ameloblastoma in young adults.

BACKGROUND: The purpose of the study was to define the most appropriate management of the giant mandibular ameloblastoma (GMA) in young adults. METHODS: A retrospective study was performed on patients with GMA <30 years old. The data collected included initial treatment, tumor margins, reconstruction, and follow-up. Patients evaluated speech, chewing, swallowing, and facial appearance after definitive treatment. RESULTS: Thirteen patients were identified with recurrent solid/multicystic disease requiring further treatment. Definitive treatment involved segmental mandibulectomy and reconstruction with free fibular flap in all patients. Seven patients had immediate reconstruction (group A) and 6 had secondary (group B). Mandibular resection was planned at least 2 cm beyond the radiological limit, free margins were achieved in all patients, and all flaps were transplanted successfully. In group A, functional score was 13.7 ± 0.45 and facial appearance score was 4.5 ± 0.49, whereas in group B were 11.16 ± 0.37 and 3.3 ± 0.5, respectively (both p < .05). CONCLUSION: Aggressive resection of the GMA and immediate reconstruction is strongly advised. © 2015 Wiley Periodicals, Inc. Head Neck 38: E1947-E1954, 2016.

Ameloblastoma: a clinical review and trends in management.

Ameloblastoma is a rare odontogenic neoplasm of the mandible and maxilla, with multiple histologic variants, and high recurrence rates if improperly treated. The current mainstay of treatment is wide local excision with appropriate margins and immediate reconstruction. Here we review the ameloblastoma literature, using the available evidence to highlight the change in management over the past several decades. In addition, we explore the recent molecular characterization of these tumors which may point towards new potential avenues of personalized treatment.

Are podoplanin and ezrin involved in the invasion process of the ameloblastomas?

The association between podoplanin and ezrin in the process of odontogenic tumors invasion has been suggested, but was not studied yet. Our purpose was to investigate the relationship between podoplanin and ezrin expressions in the odontogenic epithelium of ameloblastomas. Forty-seven ameloblastomas were analyzed by immunohistochemistry using anti-podoplanin and anti-ezrin antibodies. The expressions of both proteins were evaluated using a score method and the comparison and association between these proteins were verified, respectively, by Wilcoxon Signed-Rank test and by Spearman's rank correlation coefficient, using a statistical significance level of 0.05. The majority of tumors (87.2%) exhibited strong membranous expression of podoplanin in the peripheral cells. Cytoplasmic expression of ezrin in the peripheral cells of ameloblastomas was stronger than its membranous expression. No statistically significant correlation was observed between podoplanin and ezrin. However, there was statistically significant difference between membranous podoplanin and membranous ezrin expressions, between cytoplasmic podoplanin and membranous ezrin expressions, and between cytoplasmic podoplanin and cytoplasmic ezrin expressions. There was no statistical difference between membranous podoplanin and cytoplasmic ezrin expressions. These results suggest a synergistic role of both proteins in the process of invasion of ameloblastomas.

Regulation of IL-6 and IL-8 production by reciprocal cell-to-cell interactions between tumor cells and stromal fibroblasts through IL-1α in ameloblastoma.

Ameloblastoma is an odontogenic benign tumor that occurs in the jawbone, which invades bone and reoccurs locally. This tumor is treated by wide surgical excision and causes various problems, including changes in facial countenance and mastication disorders. Ameloblastomas have abundant tumor stroma, including fibroblasts and immune cells. Although cell-to-cell interactions are considered to be involved in the pathogenesis of many diseases, intercellular communications in ameloblastoma have not been fully investigated. In this study, we examined interactions between tumor cells and stromal fibroblasts via soluble factors in ameloblastoma. We used a human ameloblastoma cell line (AM-3 ameloblastoma cells), human fibroblasts (HFF-2 fibroblasts), and primary-cultured fibroblasts from human ameloblastoma tissues, and analyzed the effect of ameloblastoma-associated cell-to-cell communications on gene expression, cytokine secretion, cellular motility and proliferation. AM-3 ameloblastoma cells secreted higher levels of interleukin (IL)-1α than HFF-2 fibroblasts. Treatment with conditioned medium from AM-3 ameloblastoma cells upregulated gene expression and secretion of IL-6 and IL-8 of HFF-2 fibroblasts and primary-cultured fibroblast cells from ameloblastoma tissues. The AM3-stimulated production of IL-6 and IL-8 in fibroblasts was neutralized by pretreatment of AM-3 cells with anti-IL-1α antibody and IL-1 receptor antagonist. Reciprocally, cellular motility of AM-3 ameloblastoma cells was stimulated by HFF-2 fibroblasts in IL-6 and IL-8 dependent manner. In conclusion, ameloblastoma cells and stromal fibroblasts behave interactively via these cytokines to create a microenvironment that leads to the extension of ameloblastomas.

Manejo quirúrgico del ameloblastoma / Surgical management of ameloblastoma

El ameloblastoma es un tumor odontogénico de estirpe epitelial. Aunque se clasifica como una tumoración benigna, suele ser localmente agresiva presentando elevada invasión local, con gran tendencia a la recidiva y con posibilidad metastásica ocasional. Se manifiesta preferentemente durante la tercera, cuarta y quinta décadas de la vida, sin predilección por razón de sexo, aunque puede darse en cualquier grupo de edad, incluidos los niños. Lamayoría de los ameloblastomas se encuentran sobre todo enmandíbula (al nivel del ángulo y rama). En el tratamiento se debe valorar su tipología clínica (sólido, multiquístico, uniquístico, mixto o periférico), su localización y el tamaño del tumor, así como la edad y las condiciones clínicas del paciente. Presentamos una revisión de los pacientes afectos de ameloblastomas tratados en nuestro Centro durante los últimos 10 años. Se aportan datos acerca de su aparición clínica, sus características histológicas, el manejo terapéutico realizado y analizamos el seguimiento y comparamos la aparición de recidivas en los pacientes presentados. Las características clínicas, incluso si se complementan con radiografías y/omuestras histológicas, no son siempre determinantes del comportamiento biológico y, por tanto tampoco lo son del pronóstico de un ameloblastoma individual(AU)

The ameloblastoma is an odontogenic tumour of epithelial origin. Although it is classified as benign, there is usually aggressive local invasion, a great tendency to recurrence, and occasional metastatic potential. It generally appears during the third, fourth and fifth decades of life, without gender predilection, although it can occur at any age, including in children. Ameloblastomas are mostly found in the mandible (angle and branch). In treatment, its clinical type (solid, unicystic, desmoplastic, mixed or peripheral), its location and size, must be assessed, as well as the age and clinical condition of the patient. We present a review of patients diagnosed and treated for ameloblastoma in our hospital during the last 10 years.We present data on clinical appearance, histological characteristics, and therapeutic management, and we analyse and compare the rate of recurrence in these patients. The clinical features, even if they are supplemented with radiographs and/or histological samples, are not always biological determinants of its behaviour, or of the individual prognosis of the ameloblastoma(AU)

Diverse growth patterns in an intraosseous ameloblastoma: a case report.

Desmoplastic ameloblastoma (DA) is a benign but locally invasive variant of the solid/multicystic ameloblastoma (SMA). In the recent World Health Organization classification of odontogenic tumours, DA has been characterised as a variant, with specific clinical, radiographic and histopathological features. A possible 'transitional' form of DA, showing microscopic features of the desmoplastic variant together with areas typical of classic follicular or plexiform ameloblastoma, has been described as a 'hybrid' lesion of ameloblastoma (HLA). A unique case with synchronous emergence of desmoplastic and unicystic ameloblastoma (different growth patterns) in the mandible of a 50-year-old male is reported.

Ameloblastoma uniquístico, bases del tratamiento conservador. Presentación de caso clínico y actualización de la bibliografía / Conservative treatment of unicystic ameloblastoma. Case report and literature review

El ameloblastoma se define como un tumor localmente agresivo e infiltrante, con alta capacidad de recidiva. Este comportamiento agresivo e infiltrante plantea el problema de una opción conservadora o radical de tratamiento, con las alteraciones funcionales, estéticas y psicológicas que ello implica. El ameloblastoma uniquístico se describe como una lesión con cuadros morfológicos particulares, comportamiento biológico menos agresivo que el ameloblastoma común, así como también una recurrencia menor frente al tratamiento conservador. Se presenta un caso clínico con el diagnóstico de ameloblastoma uniquístico tratado de forma conservadora mediante descompresión y posterior enucleación. Se actualiza la información sobre su tratamiento(AU)

Ameloblastoma is defined as a locally aggressive, infiltrating tumor with high recurrence capacity. This aggressive and infiltrating behavior conditions the choice of conservative or radical therapy and the functional, cosmetic and psychological consequences of this choice. Unicystic ameloblastoma is described as a lesion with specific morphological pictures, less aggressive biological behavior than common ameloblastoma and less recurrence with conservative therapy. A case of unicystic ameloblastoma treated conservatively by decompression and enucleation is reported. The therapeutic options are reviewed(AU)

Ameloblastoma multiquístico mandibular tratado con terapia menos invasiva: caso clínico y revisión de la literatura / Multicystic ameloblastoma of the mandible treated by less invasive therapy: clinical case and review of the literature

El ameloblastoma es un tumor odontogénico benigno, localmente invasivo y recidivante, que constituye aproximadamente el 10% de los tumores odontogénicos. Estos tumores ocurren más frecuentemente en la mandíbula. El cuadro clínico se caracteriza generalmente por presentar deformaciones faciales, crecimiento lento y asintomático. El tratamiento depende del tipo, la localización y el tamaño del tumor, así como de la edad del paciente. En este artículo se presenta un caso de ameloblastoma multiquístico en la mandíbula, que implica a una paciente del sexo femenino de 57 años, en el cual se discuten los aspectos diagnósticos e histopatológicos, así como el tratamiento menos invasivo empleado en el caso(AU)

Ameloblastoma is a benign odontogenic tumor, locally invasive and recurrent, representing approximately 10% of odontogenic tumors. The majority of cases occur in the mandible with slow and asymptomatic growth that can lead to facial deformities. The treatment of choice is based upon on the type, location and size of the tumor, as well as the age of the patient. A case of multicystic ameloblastoma of the mandible affecting a 57 years old female patient is presented discussing the diagnostic, histological, and less invasive treatment used in the case(AU)

Ameloblastoma uniquístico, bases del tratamiento conservador. Presentación de caso clínico y actualización bibliográfica / Single cyst ameloblastoma, basis of conservative treatment. Presentation of a clinical case and update of the literature

El ameloblastoma se define como un tumor localmente agresivo e infiltrante, con una alta capacidad de recidiva. Este comportamiento agresivo e infiltrante plantea la problemática de una opción conservadora o radical de tratamiento, con las alteraciones funcionales, estéticas y psicológicas que esta última alternativa implica. El ameloblastoma uniquístico se describe como una lesión con cuadros morfológicos particulares, un comportamiento biológico menos agresivo que el ameloblastoma común, y una menor recurrencia frente a la terapia conservadora. Se presenta un caso clínico con el diagnóstico de ameloblastoma uniquístico tratado de forma conservadora mediante descompresión y posterior enucleación. Se actualiza la información sobre su tratamiento(AU)

The ameloblastoma it’s defined as a localy aggressive neoplasm with a high incidence to local recurrence. This aggressive behaviour gives two options: a conservative treatment or a radical one, with all the functional, aesthetic and psychological alterations this implies. The unicyst ameloblastoma it’s described as a disease with particular morphological aspects, a less aggressive biological behaviour than the common ameloblastoma, and less chances to reappear after a conservative treatment. Here we present a case of unicyst ameloblastoma treated in a conservative way by decompresion and resection. A review of the actual treatment methods(AU)

Ameloblastoma desmoplásico / Desmoplastic ameloblastoma

Presentamos un caso de ameloblastoma desmoplásico en una mujer de 32 años que afectaa la región media del maxilar superior. Se describen las características específicas, tantohistológicas como clínicas, de esta variante de ameloblastoma, y se insiste en su imagenradiológica similar a la de una lesión fibroósea benigna. Se indica la misma conducta terapéuticaque para el resto de los ameloblastomas intraóseos sólidos(AU)

We report a case of desmoplastic ameloblastoma in a 32 year-old female patient affectingthe region half of the upper jaw. We describe the specific characteristics, both histologicaland clinical of this variant of ameloblastoma, insisting its radiological image similar to thatof a benign fibroosseous lession. We indicate the same therapeutic conduct for the rest ofthe solid intraosseous ameloblastomas(AU)

Imuno-expressão da metalotioneída em cistos e tumores odontogênicos / Metallothionein immunoexpression in odontogenic cysts and in odontogenic tumours

Cistos e tumores odontogênicos são lesões originadas dos tecidos que formam os dentes e apresentam diferentes comportamentos biológicos. A metalotioneíra (MT) é relacionada à homeostase de metais, regulação da diferenciação e proliferação celular e inibição da apoptose. Com relação aos cistos e tumores odontogênicos, a MT poderia ter um papel na regulação da diferenciação e proliferação celuar e na inibição da apoptose, refletindo no comportamento biológico. Os objetivos são avaliar e comparar a expressão da MT entre: 1) cistos odontogêncios e tumor odontogênico ceratocístico (TOC); 2) TOC associados à Síndrome do Carcinoma Basocelular Nevóide (SCBN) e não associados; 3) tumores odontogênicos benignos. Objetivou-se também correlacionar a imuno-expressão da MT com a proliferação celular e com a inflamação. A amostra incluiu cisto radicular (CR), cisto dentígero (CD), TOC (primário associado ou não à (SCBN), cisto odontogênico ortoceratinizado (COO), ameloblastoma sólido (ABS), tumor odontogênico escamoso (TOE), tumor odontogênico adenomatóide (TOA), tumor odontogênico cístico calcificante (TOCC) e tumor odontogênico epitelial calcificante (TOEC). Foi realizada imunoistoquímica para MT, Ki-67 e PCNA...

Midkine expression correlating with growth activity and tooth morphogenesis in odontogenic tumors.

Midkine (MK; a low molecular weight heparin-binding growth factor) is a multifunctional cytokine. MK plays a role in morphogenesis of many organs including teeth through epithelial-mesenchymal interactions. We immunohistochemically examined MK expression in various human odontogenic tumors. There was no difference in positive rate and intensity of MK between benign odontogenic tumors and their malignant counterparts. Ameloblastoma showed MK localization in the peripheral columnar cells in budding processes from the parenchyma, which frequently expressed proliferating cell nuclear antigen. MK was also preferentially expressed in keratinized cells in acanthomatous ameloblastoma and keratocystic odontogenic tumor. In odontogenic mixed tumors except for odontoma, intense immunoreactivity to MK was found in epithelial follicles, the surrounding odontogenic ectomesenchymal tissue, and the basement membrane between them. Intensity in the odontogenic ectomesenchyme decreased in relation to distance from the epithelial follicles. No expression was found in tumor cells associated with production of dental hard tissues in odontogenic mixed tumors including odontoma. These findings suggested that MK is involved in the reciprocal interaction between odontogenic epithelium and odontogenic ectomesenchymal tissue in areas without dental hard tissue formation in odontogenic mixed tumors. Coexpression of MK and proliferating cell nuclear antigen was also observed in epithelial follicles and highly cellular nodules in the ectomesenchyme of odontogenic mixed tumors. MK is considered to mediate growth activity of odontogenic tumors and cell differentiation of odontogenic mixed tumors through molecular mechanisms similar to those involved in morphogenesis of the tooth.