RESUMEN
BACKGROUND: Dentigerous cysts, deemed of developmental origin, are benign odontogenic cysts characterized by a gradual growth rate. Their occurrence is twice as prevalent in men compared to women. These cysts are recognized as the most frequent developmental cysts affecting the jaws, with a typical manifestation in individuals aged 20 to 40, while infrequently identified in young children. Notably, dentigerous cysts have the potential to attain significant dimensions, resulting in painless enlargement of the jaw and subsequent deformation. OBJECTIVES: To assess the clinicopathological features and management of ten years of experience with dentigerous cysts. METHODS: A challenging cases were reported from reviewed records of the patients who were treated by the surgical intervention of various dentigerous cysts throughout the period of ten years, 2012-2022 and only histologically confirmed cases were selected, at Ramadi Teaching Hospital in addition to Rashid, Razi, Zuhur Private Hospitals and private clinics in Iraq. RESULTS: 76 patients were included in this clinicopathological research. The highest age group affected was ≤ 18 years (68.4%), 54% were male, the mandible was more affected (63.1%) than the maxilla (36.9%). Marsupialization was applied to 30.3% of the cases, while enucleation was carried out in 69.7%. CONCLUSIONS: The significance of meticulous examination of radiographs and the consequences associated with undetected and untreated ailments is affirmed by this case study. A comprehensive understanding of oral pathology serves as a valuable resource for dentists, facilitating accurate diagnosis, appropriate referrals, and the provision of anticipatory guidance to patients striving to achieve optimal oral health across various age groups.
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Quiste Dentígero , Humanos , Quiste Dentígero/cirugía , Quiste Dentígero/patología , Quiste Dentígero/diagnóstico por imagen , Masculino , Femenino , Adolescente , Adulto , Niño , Adulto Joven , Persona de Mediana Edad , Irak , Estudios RetrospectivosRESUMEN
BACKGROUND: Originating from odontogenic tissue, Odontogenic cysts are pathological cavities lined with epithelial cells and surrounded by fibrous connective tissue. This study investigated expression of CITED1 protein in different types of odontogenic cysts. MATERIAL AND METHOD: 40 keratocysts, 40 radicular cysts, and 40 dentigerous cysts were excised and processed for routine paraffin wax embedding protocol. Macroscopic and panoramic radiographies images were used for diagnosis. Demographical properties and dental parameters were recorded. Cystic tissues were stained with hematoxylin-eosin dye and CITED1 antibody. Semi-quantitative analysis was performed for immune staining. The protein-protein interaction network, hub gene detection and KEGG analysis were conducted using Cytoscape software. RESULT: Odontogenic keratocysts was imaged with 6-8 layered epithelial cells and fibrous cyst walls with inflammatory cells. Radicular cysts had stratified squamous epithelium with varying thickness, ciliated cells, and Rushton hyaline bodies. Dentigerous cysts presented hyperplastic non-keratinized epithelium, fibrous tissue, rete ridges, and inflammatory cells. CITED1 immunoexpression was highest in odontogenic keratocysts, followed by radicular cysts, and lowest in dentigerous cysts. Nuclear and cytoplasmic CITED1 expression was significantly elevated in odontogenic keratocysts compared to radicular and dentigerous cysts. The top five targets of CITED1 were identified, primarily showing enrichment in hormone and cancer related pathways. CONCLUSIONS: Positive CITED1 expression in all three types of odontogenic cysts suggest a potential role for CITED1 in the pathogenesis of odontogenic cysts, particularly in keratocysts. Further investigations are needed to elucidate the exact mechanisms underlying the differential expression of CITED1 and its implications for the development and progression of odontogenic cysts.
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Quistes Odontogénicos , Adolescente , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Quiste Dentígero/patología , Quiste Dentígero/diagnóstico por imagen , Quistes Odontogénicos/patología , Quistes Odontogénicos/metabolismo , Quiste Radicular/patología , Quiste Radicular/diagnóstico por imagen , TransactivadoresRESUMEN
BACKGROUND: To investigate the radiological and demographic features, types, distribution, and treatment methods of dentigerous cysts (DC). METHODS: Panoramic radiographs and cone beam computed tomography (CBCT) images of patients diagnosed with DC based on biopsy results between January 2020 and December 2023 were examined. In patients from different age groups, the numbers, types and locations, and radiological features of DCs, associated changes in surrounding tissues, and treatment methods used were reviewed. RESULTS: Among 95 patients with DC (66 males, 29 females), sex and age distributions were comparable between those with a single cyst (n = 86) and those with two cysts (n = 9). Of 104 DCs, 44 were central, 38 were lateral, and 22 were circumferential. DC types were not significantly affected by sex, age group, or anatomical location. Circumferential DCs often caused displacement of the mandibular canal inferiorly. While enucleation was preferred for the treatment of central DCs, circumferential DCs were treated with marsupialization. CONCLUSIONS: In this study, which is the first to evaluate the DC types on CBCT images, the central type was the most common. Circumferential DCs were mostly treated with marsupialization. CBCT imaging can assist in determining DC types, and may provide guidance for treatment planning.
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Tomografía Computarizada de Haz Cónico , Quiste Dentígero , Radiografía Panorámica , Humanos , Quiste Dentígero/diagnóstico por imagen , Quiste Dentígero/patología , Femenino , Masculino , Adulto , Adolescente , Turquía , Adulto Joven , Persona de Mediana Edad , Niño , Imagenología Tridimensional/métodos , Estudios Retrospectivos , AncianoRESUMEN
BACKGROUND: Benign odontogenic lesions (BOLs) can cause severe jaw bone defects and compromise the quality of life of patients. Extracellular vesicles (EVs) are well-established and versatile players in mediating pathophysiological events. EVs in the interstitial space (tissue-derived EVs or Ti-EVs) possess higher specificity and sensitivity in disease-related biomarker discovery. However, the role of Ti-EV-loaded proteins in mediating the development of BOLs has remained untapped. Herein, we aim to explore the contribution of Ti-EV-loaded proteins to the development of BOLs. METHODS: Samples were obtained from 3 with dental follicle, 3 with dentigerous cyst (DC), 7 with odontogenic keratocyst (OKC), and 3 patients with ameloblastoma (AM). Tissue-derived EVs were then extracted, purified, and validated using ultracentrifugation, transmission electron microscopy, and western blotting. Proteins from Ti-EVs were analyzed using LC-ESI tandem mass spectroscopy and differentially expressed proteins were screened, which was then validated by immunohistochemistry and immunofluorescence assays. RESULTS: The protein profile of Ti-EVs in each group was mapped by LC-MS analysis. The top 10 abundant proteins in BOL-derived Ti-EVs were COL6A3, COL6A1, ALB, HIST1H4A, HBB, ACTB, HIST1H2BD, ANXA2, COL6A2 and FBN1. Additionally, unique proteins in the Ti-EVs from various lesions were identified. Moreover, focal adhesion kinase (FAK) and myeloid differentiation primary response 88 (MyD88) showed higher expressions in Ti-EVs derived from OKC and AM, which were confirmed by immunohistochemistry and immunofluorescence staining. CONCLUSIONS: Ti-EVs containing FAK and MyD88 might be related to the development of OKC and AM, which can be potential therapeutic targets.
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Ameloblastoma , Quiste Dentígero , Vesículas Extracelulares , Proteómica , Humanos , Vesículas Extracelulares/metabolismo , Proteómica/métodos , Ameloblastoma/metabolismo , Ameloblastoma/patología , Ameloblastoma/diagnóstico , Quiste Dentígero/metabolismo , Quiste Dentígero/patología , Quiste Dentígero/diagnóstico , Quistes Odontogénicos/metabolismo , Quistes Odontogénicos/patología , Adulto , Femenino , Masculino , Saco Dental/metabolismo , Saco Dental/patología , Saco Dental/citología , Tumores Odontogénicos/metabolismo , Tumores Odontogénicos/patología , Tumores Odontogénicos/diagnóstico , Inmunohistoquímica , Adolescente , Western Blotting , Biomarcadores/metabolismo , Biomarcadores/análisisRESUMEN
Glandular odontogenic cysts (GOCs) and dentigerous cysts may show mucous metaplasia. Central mucoepidermoid carcinoma is very rare and mostly associated with dental cysts. It is hypothesized that odontogenic cysts showing mucus differentiation in their lining, have a propensity to transform into MEC. The present study is the first attempt to explore the relationship between odontogenic cysts [GOCs and dentigerous cysts with mucus metaplasia (DCMM)] and MEC by evaluating immunoexpression of MUC5AC and MUC2. Immunoexpression of MUC5AC and MUC2 was evaluated semiquantitatively in GOCs (20 cases), DCMMs (20 cases), and MECs (20 cases). The percentage of positive cells, intensity, and localization of immunoexpression were assessed for each marker in all cases. Of GOCs, DCMMs, and MECs cases, 85%, 70%, and 80%, respectively, were immunopositive for MUC5AC. Strong cytoplasmic immunoreactivity for MUC5AC was noted, particularly in mucous cells present diffusely within MECs. However, the immunoreactivity was limited to the epithelial lining of GOCs and DCMMs. Most of the MECs (60%) showed more than 25% positivity for MUC5AC, followed by GOCs, and the least in DMMCs. Mild cytoplasmic and nuclear positivity of MUC2 was noted only in epithelial lining cells of 70% GOCs and 45% DCMMs. Whereas, 55% of MECs displayed moderate to strong cytoplasmic and membranous immunopositivity for MUC2 exclusively within mucous cells. As MECs showed strong MUC5AC immunoreactivity in mucous cells, immunoexpression of MUC5AC in odontogenic cysts with mucus cells can possibly explain the pathogenesis of MEC from cysts. However, the variable expression of MUC2 did not give any strong evidence regarding its role as a marker.
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Carcinoma Mucoepidermoide , Quiste Dentígero , Quistes Odontogénicos , Humanos , Carcinoma Mucoepidermoide/patología , Quiste Dentígero/patología , Quistes Odontogénicos/patología , Células Epiteliales/patología , Metaplasia/patología , Mucina 5AC , Mucina 2RESUMEN
AIM: Cyst formation of the jaws is frequently accompanied by the proliferation of odontogenic epithelial cells located in the periodontal ligament (PDL), which consists of heterozygous cells and includes the most fibroblasts. The lining epithelium of radicular cyst, an odontogenic cyst of inflammatory origin, is derived from the proliferation of the remnants of the Hertwig epithelial root sheath (odontogenic epithelial cell rests of Malassez; ERMs) in the PDL. ERMs are maintained at a lower proliferative state under physiological conditions, but the regulatory mechanisms underlying the inflammation-dependent enhanced-proliferative capabilities of ERMs are not fully understood. The aim of this study was to evaluate the effects of cytokine pathway association between TGF-ß signalling and IL-1ß signalling on the regulation of odontogenic epithelial cell proliferation using radicular cyst pathological specimens and odontogenic epithelial cell lines. METHODOLOGY: Immunofluorescence analyses were performed to clarify the expression levels of Smad2/3 and Ki-67 in ERMs of 8-week-old mouse molar specimens. In radicular cyst (n = 52) and dentigerous cysts (n = 6) specimens from human patients, the expression of p65 (a main subunit of NF-κB), Smad2/3 and Ki-67 were investigated using immunohistochemical analyses. Odontogenic epithelial cells and PDL fibroblastic cells were co-cultured with or without an inhibitor or siRNAs. Odontogenic epithelial cells were cultured with or without TGF-ß1 and IL-1ß. The proliferative capabilities and Smad2 phosphorylation levels of odontogenic epithelial cells were examined. RESULTS: Immunohistochemically, Smad2/3-positivity was increased, and p65-positivity and Ki-67-positivity were decreased both in ERMs and in the epithelial cells in dentigerous cysts, a non-inflammatory developmental cyst. In contrast, p65-positive cells, along with the expression of Ki-67, were increased and Smad2/3-positive cells were decreased in the lining epithelia of radicular cysts. Co-culture experiments with odontogenic epithelial cells and PDL fibroblastic cells revealed that PDL cells-derived TGF-ß1/2 and their downstream signalling suppressed odontogenic epithelial cell proliferation. Moreover, TGF-ß1 stimulation induced Smad2 phosphorylation and suppressed odontogenic epithelial cell proliferation, while IL-1ß stimulation reversed these phenotypes through p65 transactivation. CONCLUSIONS: These results suggest that IL-1ß-p65 signalling promotes odontogenic epithelial cell proliferation through suppressing TGF-ß-Smad2 signalling, which would be involved in the pathogenesis of radicular cysts.
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Quiste Dentígero , Quistes Odontogénicos , Quiste Radicular , Humanos , Animales , Ratones , Quiste Radicular/patología , Factor de Crecimiento Transformador beta1 , Quiste Dentígero/complicaciones , Quiste Dentígero/metabolismo , Quiste Dentígero/patología , Antígeno Ki-67 , Descanso , Quistes Odontogénicos/patología , Células Epiteliales , Epitelio/patología , Proliferación Celular , Factor de Crecimiento Transformador beta/metabolismo , Interleucina-1betaRESUMEN
Dentigerous cysts are known as the second most common type of cyst in the jaws. The cyst is one of the lesions occurred frequently in the posterior body of the mandible and is often related to the unerupted third molar and forms around the crown of the unerupted tooth attaching at the cementoenamel junction. Such characteristic appearances are the diagnostic points differentiating from ameloblastoma or odontogenic keratocyst. However, it would be hard for us to diagnose it as a dentigerous cyst if the lesion does not show its typical appearance. We experienced two cases of dentigerous cysts which did not form around the crown of the unerupted tooth on radiologically. Both cysts were relatively large and resorbed adjacent teeth roots. Therefore, an ameloblastoma or an odontogenic keratocyst was suspected rather than a dentigerous cyst as the imaging diagnosis. The biopsy revealed that the lesion was a "dentigerous cyst" in one of the cases and "developmental cyst with inflammation" in another case. After the excision, the histopathological diagnosis was a dentigerous cyst with inflammation in both cases. This report shows the two cases of dentigerous cysts focusing on panoramic radiography and CT images. Also, we discuss the differential diagnosis by reconsidering those diagnostic points.
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Ameloblastoma , Quiste Dentígero , Quistes Odontogénicos , Diente no Erupcionado , Humanos , Quiste Dentígero/diagnóstico por imagen , Quiste Dentígero/patología , Ameloblastoma/diagnóstico por imagen , Radiografía Panorámica , Quistes Odontogénicos/diagnóstico por imagen , Inflamación , Tomografía Computarizada por Rayos XRESUMEN
PURPOSE: We used proteomic sequencing and experimental verification to identify the potential ferroptosis-related proteins in ameloblastoma. METHODS: Samples of ameloblastoma (n = 14) and normal gingival tissues (n = 5) were collected for proteomic sequencing to identify differentially expressed proteins (DEPs) in ameloblastoma. Ferroptosis-related genes were downloaded from FerrDb V2, which were then compared with DEPs to obtain ferroptosis-related DEPs (FR-DEPs). A functional enrichment analysis was performed, and a protein-protein interaction network was built. The hub proteins were screened using the Cytoscape software, and potential drugs targeting them were retrieved from the DrugBank database. A hub protein was selected for immunohistochemical validation, and its expression was assessed in ameloblastomas, odontogenic keratocysts, dentigerous cysts, and normal gingival tissues. The primary ameloblastoma cells were cultured to explore the effect of the protein on the migratory properties of the tumour cells. RESULTS: A total of 58 FR-DEPs were screened, and six hub proteins were identified: mTOR, NFE2L2, PRKCA, STAT3, EGFR, and CDH1. Immunohistochemical analysis showed that mTOR expression was upregulated in ameloblastomas compared with that in odontogenic keratocysts, dentigerous cysts, and normal gingival tissues. p-mTOR was highly expressed in ameloblastomas, with a positivity rate of 83.3%. In addition, rapamycin, an inhibitor of mTOR, can inhibit the migratory capacity of primary cultured ameloblastoma cells. CONCLUSION: Our results revealed the ferroptosis-related proteins in ameloblastomas and their underlying biological processes. Additionally, mTOR was overexpressed and was found to be associated with the aggressiveness of ameloblastomas, which may be a potential target for future treatments.
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Ameloblastoma , Quiste Dentígero , Ferroptosis , Quistes Odontogénicos , Humanos , Quiste Dentígero/metabolismo , Quiste Dentígero/patología , Ameloblastoma/genética , Ameloblastoma/metabolismo , Ameloblastoma/patología , Proteómica , Inmunohistoquímica , Quistes Odontogénicos/metabolismo , Quistes Odontogénicos/patología , Serina-Treonina Quinasas TOR/genéticaRESUMEN
BACKGROUND: PEA3 transcription factor has been identified as a downstream target of the MAPK and PI3K pathways, and PEA3 overexpression has been observed in a variety of tumor types. We aimed to evaluate PEA3 expression in odontogenic cysts and tumors and compare the expression among odontogenic lesions. In addition, the correlations between PEA3 expression and clinicopathological characteristics of conventional ameloblastoma and unicystic ameloblastoma were investigated. METHODS: This study was performed on 165 samples of odontogenic cysts and tumors including 20 dentigerous cysts, 20 odontogenic keratocysts, 16 adenomatoid odontogenic tumors, 5 ameloblastic fibromas, 45 unicystic ameloblastomas, and 59 conventional ameloblastomas. The sections were immunohistochemically stained with mouse monoclonal anti-PEA3 antibody and PEA3 expression was evaluated as the immunoreactive score. RESULTS: PEA3 expression was absent in all dentigerous cysts (DCs) and odontogenic keratocysts, while all adenomatoid odontogenic tumors showed either no (75%) or low (25%) expression of PEA3. Most of the ameloblastic fibromas (60%) displayed no PEA3 expression. A high expression of PEA3 was observed in a substantial number of unicystic ameloblastomas (48.9%) and conventional ameloblastomas (49.2%) in our study. PEA3 expression in DCs, odontogenic keratocysts and adenomatoid odontogenic tumors were significantly different from that in conventional ameloblastomas and that in unicystic ameloblastomas (p < 0.05). The expression of PEA3 was significantly different in the age groups of unicystic ameloblastomas and histological subtypes of conventional ameloblastomas (p < 0.05). CONCLUSION: PEA3 overexpression is predominant in unicystic ameloblastomas and conventional ameloblastomas compared to other odontogenic lesions, indicating a pivotal role of PEA3 as a downstream effector of MAPK pathway in these two odontogenic lesions.
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Ameloblastoma , Quiste Dentígero , Fibroma , Neoplasias Maxilomandibulares , Quistes Odontogénicos , Tumores Odontogénicos , Ameloblastoma/metabolismo , Quiste Dentígero/patología , Neoplasias Maxilomandibulares/patología , Quistes Odontogénicos/patología , Tumores Odontogénicos/patología , Fosfatidilinositol 3-Quinasas , HumanosRESUMEN
BACKGROUND: Odontogenic keratocysts constitute 10%-20% of odontogenic cysts and exhibit a distinctive corrugated parakeratinized lining epithelium. Considering that cornified envelope formation is an important phenomenon during keratinocyte differentiation, this study aimed to clarify the characteristics of cornified envelope formation in odontogenic keratocysts. METHODS: We investigated the cellular distribution of cornified envelope-related proteins (transglutaminases and their substrates), as well as the upstream regulatory protein c-Fos, by immunohistochemical analysis of the lining epithelium of 20 odontogenic keratocysts. We examined the corresponding mRNA levels by quantitative polymerase chain reaction. Ten dentigerous cysts served as control non-keratinized cysts. RESULTS: The distributions of transglutaminase and their substrates except loricrin and small protein-rich protein 1a significantly differed between odontogenic keratocysts and dentigerous cysts. There was no significant difference in c-Fos expression between odontogenic keratocysts and dentigerous cysts. The mRNA levels of transglutaminases and their substrates were significantly higher in odontogenic keratocysts than in dentigerous cysts. However, c-Fos mRNA levels did not significantly differ between groups. CONCLUSION: Surprisingly, the overall appearance of cornified envelope-related proteins of odontogenic keratocysts was consistent with the characteristics of non-keratinized oral mucosa identified in previous studies. These findings indicate that the contribution of cornified envelope-related molecules in odontogenic keratocysts is similar to that in non-keratinized oral epithelium, rather than keratinized oral epithelium, suggesting that odontogenic keratocysts are not genuine keratinized cysts. The upregulation of cornified envelope-related genes in odontogenic epithelium could be an important pathognomonic event during odontogenic keratocyst development.
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Quiste Dentígero , Quistes Odontogénicos , Humanos , Quiste Dentígero/patología , Quistes Odontogénicos/genética , Quistes Odontogénicos/patología , Epitelio/patología , TransglutaminasasRESUMEN
Cysts encountered in the head and neck typically arise from epithelium that would normally be programmed to form teeth or tooth-supporting structures (odontogenic epithelium). These cysts come with a confusing array of similar-sounding names and histopathologic features that are sometimes shared between conditions. Here we describe and contrast the relatively-common lesions: hyperplastic dental follicle, dentigerous cyst, radicular cyst, buccal bifurcation cyst, odontogenic keratocyst, glandular odontogenic cyst, and the less-common gingival cyst of the new-born and thyroglossal duct cyst. The goal of this review is to help clarify and simplify these lesions for the general pathologist, pediatric pathologist, and surgeon.
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Quiste Dentígero , Quistes Odontogénicos , Tumores Odontogénicos , Quiste Radicular , Humanos , Niño , Quiste Dentígero/diagnóstico , Quiste Dentígero/patología , Quistes Odontogénicos/diagnóstico , Quistes Odontogénicos/patología , Quiste Radicular/patología , Epitelio/patologíaRESUMEN
BACKGROUND: Reports on the proteomic studies of ameloblastoma and other common odontogenic lesions are limited. We thus explored the differential proteins among ameloblastoma, odontogenic keratocyst, dentigerous cyst, and normal gingival tissue using proteomics and identified hub proteins involved in the local aggressiveness and recurrence of ameloblastoma. METHODS: Samples were obtained from 14 patients with ameloblastoma, 6 with odontogenic keratocyst, 9 with a dentigerous cyst, and 5 with normal gingival tissue. Proteins were then extracted, purified, quantified, and analysed using Easy-nLC chromatography and mass spectrometry. Further functional annotation and enrichment analyses were performed using Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes on the target protein collection. Protein clustering and protein-protein interaction network analyses were used to screen the hub proteins. Proteins with significant interactions were screened according to their degree index. These results were verified by immunohistochemical staining. Proteins meeting the screening criteria of expression difference ploidy >1.2-fold (upregulation and downregulation) and p < 0.05 were considered differential proteins. RESULTS: In ameloblastoma, 808 differential proteins were upregulated and 505 were downregulated compared with those in odontogenic keratocyst; 309 were upregulated and 453 were downregulated compared with those in dentigerous cyst; and 2210 were upregulated and 829 were downregulated compared with those in normal gingival tissue. The three groups of differential proteins were associated with cellular exosomes, antigen binding, complement activation, human papillomavirus infection, focal adhesion, cell adhesion molecules, and metabolic pathways. CONCLUSION: CDH3 is associated with the local aggressiveness and recurrence of ameloblastoma and is a potential therapeutic target.
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Ameloblastoma , Quiste Dentígero , Quistes Odontogénicos , Tumores Odontogénicos , Humanos , Ameloblastoma/genética , Ameloblastoma/patología , Quiste Dentígero/genética , Quiste Dentígero/patología , Proteómica , Quistes Odontogénicos/genética , Tumores Odontogénicos/genéticaRESUMEN
Introdução: Os cistos e tumores odontogênicos são lesões que apresentam comportamento biológico heterogêneo e patogênese ainda não totalmente esclarecida. A Yes-associated protein (YAP) atua como um regulador transcricional de genes envolvidos na proliferação celular e na apoptose, participando da ativação de vias associadas ao crescimento cístico e à progressão neoplásica. Objetivo: Analisar a expressão imuno-histoquímica da proteína YAP e correlacioná-la com marcadores envolvidos na proliferação celular e na apoptose em lesões odontogênicas epiteliais benignas. Metodologia: A amostra consistiu de 95 casos de lesões odontogênicas - 25 cistos dentígeros (CDs), 30 CO não sindrômicos (COs), 30 AMB convencionais (AMB-Cs) e 10 AMB unicísticos (AMB-Us) -, além de 10 espécimes de folículo dentários (FD). Foi realizada coleta dos dados clinico-demográficos dos casos, bem como análise morfológica para melhor caracterização da amostra. Os cortes histológicos foram submetidos à técnica imuno-histoquímica através da utilização dos anticorpos YAP, ciclina D1, Ki-67 e Bcl-2, e a análise da expressão destes foi realizada quali-quantitativamente, mediante metodologia adaptada. Os dados coletados seguiram para análise descritiva e estatística (p ≤ 0,05). Resultados: Houve discreta predileção por mulheres (n = 55; 57,6%) e por indivíduos na faixa etária dos 21 aos 40 anos (n = 50; 47,6%), sendo a região posterior de mandíbula mais afetada (64%). A análise da imunoexpressão de YAP revelou maiores níveis de expressão em COs, especialmente nas camadas basal e parabasal, seguido dos AMB-Us e AMB-Cs, que demonstraram moderada imunorreatividade, predominantemente nas células periféricas. Além disso, houve diferenças significativas quanto à imunoexpressão de YAP entre os grupos analisados, com existência de correlações positivas e estatisticamente significativas entre YAP e ciclina D1 em CDs e AMB-Us, e entre YAP e Ki-67 em AMB-Us (p < 0,05). Todavia, entre a imunoexpressão YAP e Bcl-2, foi verificada ausência de correlação estatisticamente significativa. Conclusões: A YAP pode exercer influência sobre a proliferação celular do epitélio de cistos e tumores odontogênicos, auxiliando, assim, na progressão das diferentes lesões odontogênicas (AU).
Background: Odontogenic cysts and tumors present heterogeneous biological behavior, and their etiopathogenesis is not fully understood yet. Yes-associated protein (YAP) acts as a transcriptional regulator of genes involved in cell proliferation and apoptosis, activating pathways associated with cystic growth and neoplastic progression. Objective: To analyze the immunohistochemical expression of YAP protein and correlate it with markers involved in cell proliferation and apoptosis in benign epithelial odontogenic lesions. Methods: The sample consisted of 95 cases of odontogenic lesions - 25 dentigerous cysts (DCs), 30 non-syndromic odontogenic keratocyst (OKCs), 30 conventional AMB (C-AMBs), and 10 unicystic AMB (UAMBs) -, in addition to 10 specimens of dental follicles (DF). Clinicodemographic data collection was carried out, as well as morphological analysis for better characterization of the sample. The histological sections were submitted to the immunohistochemical technique using YAP, cyclin D1, Ki-67, and Bcl-2 antibodies, and their immunoexpression analysis was performed qualitatively and quantitatively, through an adapted methodology. The collected data were submitted for descriptive and statistical analysis (p ≤ 0.05). Results: There was a slight predilection for women (n = 55; 57.6%) and individuals aged between 21 and 40 years (n = 50; 47.6%), with the posterior region of the mandible as the most affected site (64%). Analysis of YAP immunoexpression revealed higher expression levels in OKCs, especially in the basal and parabasal layers, followed by U-AMBs and C-AMBs, which showed moderate immunoreactivity, predominantly in peripheral cells. In addition, there were significant differences in YAP immunoexpression between the analyzed groups, with positive and statistically significant correlations between YAP and cyclin D1 in DCs and U-AMBs, and between YAP and Ki-67 in U-AMBs (p < 0.05). However, between YAP and Bcl-2 immunoexpression, there was no statistically significant correlation. Conclusions: YAP may influence on the cell proliferation of odontogenic cysts and tumors epithelium, thus helping with the progression of the different odontogenic lesions (AU) .
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Proliferación Celular , Proteínas Señalizadoras YAP/metabolismo , Proteínas Coactivadoras Transcripcionales con Motivo de Unión a PDZ/metabolismo , Quiste Dentígero/patología , Biomarcadores de Tumor , Registros Médicos , Estudios Retrospectivos , Interpretación Estadística de Datos , Apoptosis , Quiste Odontogénico Calcificado/patología , Estadísticas no Paramétricas , Proteínas Inhibidoras de la Diferenciación , Estudio Observacional , Hallazgos Morfológicos y MicroscópicosRESUMEN
The aim of this study was to evaluate the immunoexpression of chemokine CXCL12 and its receptor CXCR4 in radicular cysts (RCs), dentigerous cysts (DCs), and odontogenic keratocysts (OKCs), and to correlate the findings with morphologic parameters of RCs (inflammatory infiltrate and cystic epithelium). Twenty RCs, 20 DCs, and 20 OKCs were submitted to immunohistochemistry. The percentages of cytoplasmic (CXCL12 and CXCR4) and nuclear (CXCR4) staining in epithelial and fibrous capsule cells were determined. RCs and DCs exhibited higher epithelial expression of CXCL12 than OKCs ( P <0.05). The expression of CXCL12 in the fibrous capsule was higher in DCs than in RCs and OKCs ( P <0.05). Higher cytoplasmic expression of CXCR4 was observed in the epithelial lining and fibrous capsule of RCs and DCs compared with OKCs ( P <0.05). In the fibrous capsule, DCs exhibited higher nuclear expression of CXCR4 than OKCs ( P <0.05). No significant differences in the immunoexpression of CXCL12 or CXCR4 were observed according to the morphologic parameters of RCs ( P >0.05). Strong positive correlations were found between cytoplasmic and nuclear expression of CXCR4 in the epithelial lining of RCs and DCs and in the fibrous capsule of all groups ( P <0.05). The results suggest the participation of CXCL12 and CXCR4 in the pathogenesis of RCs, DCs, and OKCs. These proteins may be particularly relevant for the development of odontogenic cysts with less aggressive biological behavior, irrespective of their nature (inflammatory or developmental). In RCs, the expression of CXCL12 and CXCR4 may not be related to the intensity of the inflammatory infiltrate or the status of cystic epithelium.
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Quimiocina CXCL12 , Quiste Dentígero , Quistes Odontogénicos , Tumores Odontogénicos , Quiste Radicular , Receptores CXCR4 , Humanos , Quiste Dentígero/metabolismo , Quiste Dentígero/patología , Quistes Odontogénicos/metabolismo , Quiste Radicular/patología , Transducción de SeñalRESUMEN
OBJECTIVES: Odontogenic lesions evolve as a result of altered dental development. This study aimed to evaluate the prevalence and the coinfection of Epstein-Barr virus (EBV) and Kaposi sarcoma-associated herpesvirus (KSHV) in radicular cysts, dentigerous cysts, odontogenic keratocysts, and ameloblastomas. METHODS: Polymerase chain reaction (PCR) was used to analyse 66 cases of odontogenic lesions for the presence of EBV-DNA and KSHV-DNA. These lesions were 15 radicular cysts, 16 dentigerous cysts, 18 odontogenic keratocysts, and 17 ameloblastomas. RESULTS: EBV-DNA was detected in 24 (36.4%) of the studied samples as follows: 6 samples (40.0%) of radicular cysts, 4 (25.0%) of dentigerous cysts, 10 (55.6 %) of odontogenic keratocysts, and 4 (23.5%) of ameloblastomas (P = .168). KSHV-DNA was found in 16 (24.2%) of the studied samples as follows: 1 sample (6.7%) of radicular cysts, 6 (37.5%) of dentigerous cysts, 8 (44.4 %) of odontogenic keratocysts, and 1 (5.9%) of ameloblastomas (P = .001). Additionally, EBV and KSHV were positively correlated in all studied samples (P = .002). CONCLUSIONS: Both EBV and KSHV are found in odontogenic cysts and ameloblastomas. KSHV and EBV are more prevalent in odontogenic keratocysts than in other studied odontogenic lesions. Further, there is a high prevalence of EBV and KSHV coinfection in odontogenic cysts and ameloblastomas.
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Coinfección , Infecciones por Virus de Epstein-Barr , Quistes Odontogénicos , Quiste Radicular , Sarcoma de Kaposi , Humanos , Ameloblastoma , Coinfección/epidemiología , Quiste Dentígero/patología , ADN , Infecciones por Virus de Epstein-Barr/epidemiología , Herpesvirus Humano 4 , Herpesvirus Humano 8 , Quistes Odontogénicos/epidemiología , Quistes Odontogénicos/patología , Prevalencia , Quiste Radicular/patología , Sarcoma de Kaposi/epidemiologíaRESUMEN
The osteolytic activity of odontogenic cysts and tumors is directly associated with their growth and aggressiveness. The influence of proteins expressed by epithelial and mesenchymal cells on this biological event differs between indolent cystic lesions, aggressive cystic lesions, and odontogenic tumors. The objective of this study was to compare the immunohistochemical expression of factors that stimulate (receptor activator of nuclear factor kappa-Β ligand - RANKL, cathepsin K - CatK and matrix metallopeptidase 8 - MMP-8) and inhibit (osteoprotegerin - OPG) osteoclastogenesis between dentigerous cyst (DC), glandular odontogenic cyst (GOC), odontogenic keratocyst (OKC), and ameloblastoma (AB). Paraffin-embedded sections of nine DCs, nine GOCs, 20 OKCs, 21 ABs, and four dental follicles (DFs) were subjected to immunohistochemistry. Immunoreactivity was analyzed semiquantitatively and quantitatively in epithelium and connective tissue, respectively. The proteins were immunoexpressed in epithelial and mesenchymal cells of all lesions studied. The expression of RANKL and CatK was higher in OKC, AB, and GOC (p<0.005). Higher expression of OPG was found in DF and DC compared to the other markers (p<0.005). MMP-8 expression was high in GOC and OKC. This study demonstrated the differential expression of factors that inhibit and stimulate bone resorption during the development of DC, GOC, OKC, and AB. Higher expression of RANKL and CatK was observed in more aggressive lesions. OPG appears to be one of the molecules responsible for the slower growth of DC.
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Ameloblastoma , Quiste Dentígero , Quistes Odontogénicos , Tumores Odontogénicos , Humanos , Quiste Dentígero/metabolismo , Quiste Dentígero/patología , Metaloproteinasa 8 de la Matriz , Quistes Odontogénicos/patología , Ameloblastoma/metabolismo , Ameloblastoma/patología , Tumores Odontogénicos/patologíaRESUMEN
Background: Interleukin 8 (IL-8) is a chemotactic cytokine released by various cells including leukocytes, endothelial cells, and epithelial cells. IL-8 has multiple functions in inflammation, tumour invasion, or angiogenesis. Human odontogenic cystic lesions are chronic and frequently inflamed. Tissue-derived extracellular vesicles (Ti-EVs) are widely present in various tissues and could more accurately reflect the characteristics of the primary tissue. However, the involvement of IL-8 in Ti-EVs of human odontogenic lesions is still unclear. This study aimed to explore the expression of IL-8 in Ti-EVs of human odontogenic lesions and the potential roles of Ti-EVs that carried IL-8. Methods: Fresh tissue samples of dentigerous cyst (DC, n = 5) and odontogenic keratocyst (OKC, n = 5) were collected for Ti-EVs isolation. Ti-EVs were characterised by transmission electron microscopy and nano-flow cytometry analysis. The cytokine profile of Ti-EVs was explored by cytokine antibody array. The IL-8 expression was examined by immunochemical staining in tissue of odontogenic lesions (DC, n =12; OKC, n =28). Antioxidants (N-acetyl-L-cysteine and diphenyleneiodonium) were employed to treat HaCaT cells, and the expression of IL-8 was detected by enzyme-linked immunosorbent assay. The gene expression of MMP9 was explored by quantitative real-time polymerase chain reaction in co-culture system of fibroblasts of OKC with Ti-EVs. Results: Compared with DC, the expression of IL-8 in Ti-EVs and fixed tissue specimens of OKC was markedly upregulated. The antioxidants decreased the expression level of IL-8 protein in the supernatant of HaCaT cells. The Ti-EVs treatment (10 µg/ml) of fibroblasts significantly induced the MMP9 mRNA expressions in OKC fibroblasts. Conclusions: IL-8 was upregulated in Ti-EVs of OKC and might be involved in the tissue destruction of OKC.
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Quiste Dentígero , Interleucina-8/metabolismo , Quistes Odontogénicos , Tumores Odontogénicos , Quiste Dentígero/metabolismo , Quiste Dentígero/patología , Células Endoteliales/metabolismo , Humanos , Interleucina-8/genética , Metaloproteinasa 9 de la Matriz , Quistes Odontogénicos/metabolismoRESUMEN
AIM: This study aimed to evaluate the contribution of the MRI and CT results to the differential diagnosis of histopathologically different odontogenic cysts. BACKGROUND: Odontogenic cysts are commonly seen in the jaw bone and their surgical operations have an important place in the practice of maxillofacial surgery; treatment options for these cysts differ according to their histopathology. Differential results that can be obtained from the radiological evaluations of different cyst groups will allow the surgeon to plan a more accurate approach at the beginning of the operation. In this study, computed tomography (CT) and magnetic resonance imaging (MRI) results of different cyst groups were interpreted together with their histopathological diagnosis. METHODS: CT and MRI results of 17 patients aged between 19-61 were evaluated, whose histopathological diagnosis consisted of 3 radicular cysts (RC), a total of 9 odontogenic keratocysts (OKC) of which 4 were inflamed, and a total of 5 dentigerous cysts (DC) of which one of them was inflammatory. RESULTS: In the CT scan, all cysts showed lytic, a sclerotic surrounding, and showed MRI peripheral enhancement, whereas solid nodular enhancement was only observed in OKCs. Edema and/or air in the surrounding bone medulla was observed in the infected lesions. OKC was heterogeneous, whereas RC and DC were more homogeneous. Diffusion restriction was observed to be frequent in OKCs. The OKCs were ellipsoidal in appearance and were located parallel to the long axis of the bone, and their dimensions were observed to be larger than the other cysts. OKCs may be accompanied by unerupted teeth. Radicular cysts were located perpendicular to the long axis of the bone and were globular in appearance, and their dimensions were smaller and more homogeneous compared to the OKCs. Dentigerous cysts are also accompanied by an unerupted tooth, and their peripheral enhancement is minimal and homogeneous. However, dentigerous cysts can be dense in content and smaller in size, and ellipsoidal localization is more common than OKCs. CONCLUSION: In addition to classic panoramic radiography in the evaluation and differential diagnosis of maxillary and mandibular lesions, CT and MRI evaluations can provide helpful information to the surgeon and pathologist in making the diagnosis and may further help plan the operation.
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Quiste Dentígero , Quistes Odontogénicos , Quiste Radicular , Humanos , Adulto Joven , Adulto , Persona de Mediana Edad , Quiste Radicular/diagnóstico por imagen , Quiste Radicular/patología , Quiste Dentígero/diagnóstico por imagen , Quiste Dentígero/patología , Diagnóstico Diferencial , Quistes Odontogénicos/diagnóstico por imagen , Quistes Odontogénicos/patología , Tomografía Computarizada por Rayos X , Imagen por Resonancia MagnéticaRESUMEN
We aimed to compare mitochondrial function, mitochondrial dynamics, apoptosis, and necroptosis between odontogenic cysts/tumors, including radicular cysts, dentigerous cysts, ameloblastoma, vs. dental follicles as control. We demonstrated that mitochondrial dysregulation and imbalanced mitochondrial dynamics were observed in ameloblastoma. Apoptosis was increased in dentigerous cysts, and ameloblastoma, while necroptosis was suppressed in ameloblastoma. Necroptosis in radicular cysts was higher than that of control, suggesting that the inflammation-associated cell death occurred in radicular cysts. Our findings suggest ameloblastoma exhibited mitochondrial dysfunction, decreased mitochondrial fusion, and potential apoptosis. Therefore, alleviating mitochondrial dysregulation and apoptosis may be novel-targeted therapy for odontogenic cysts and tumors.