RESUMEN
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
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
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
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
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.
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Ameloblastoma/patología , Quiste Dentígero/patología , Mitocondrias/metabolismo , Quiste Radicular/patología , Especies Reactivas de Oxígeno/metabolismo , Adolescente , Adulto , Anciano , Ameloblastoma/metabolismo , Estudios de Casos y Controles , Muerte Celular , Niño , Estudios Transversales , Quiste Dentígero/metabolismo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Dinámicas Mitocondriales , Necroptosis , Quiste Radicular/metabolismo , Adulto JovenRESUMEN
Objective: To assess and compare the stromal expression of CD10 in OKC, dentigerous and radicular cysts. Materials and Methods: This comparative, cross sectional study was conducted at Armed Forces Institute of Pathology (AFIP), Rawalpindi, from Jan 2017 to Dec 2017. Total sixty cases comprising 20 of each OKC, Dentigerous and Radicular cysts were included in this study. Hematoxylin and eosin (H and E) sections were performed followed by immunohistochemical staining for CD10 antibody. Expression of CD10 was evaluated and compared. Results were analyzed by using SPSS version 20.0. Chi Square test was performed with P value < 0.05 was considered as significant. Results: A total of 60 cases, 20 of each OKC, dentigerous and radicular cysts were taken. In our study, 38 (63.3%) male and 22 (36.7%) female patients with the mean age of 32 ± 15 (mean ± SD) were included. Percentage of CD10 positive cells were highest in sub-epithelial stroma of OKC (95% cases) as compared to radicular and dentigerous cysts (60 and 70%) with highest number of cases showing intense staining in OKC 13(65%) as compared to other odontogenic cysts i-e 4(20%) and 2 (10%) respectively. There was a statistically significant association between odontogenic cysts and proportional score, intensity score and combined score of stromal CD10 expression (P=0.009, p=0.001 and p=0.000). Conclusion: In this study, we found that highest stromal CD10 expression in OKC as compared to dentigerous and radicular cyst, which might be due to aggressive behaviour and increased risk of recurrence in OKC. Expression of CD10 marker will further aid the clinician to plan appropriate surgical intervention and keep regular follow-ups to identify recurrences.
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Quiste Dentígero/metabolismo , Recurrencia Local de Neoplasia/metabolismo , Neprilisina/metabolismo , Quistes Odontogénicos/metabolismo , Quiste Radicular/metabolismo , Adulto , Estudios Transversales , Quiste Dentígero/patología , Femenino , Humanos , Inmunohistoquímica/métodos , Masculino , Recurrencia Local de Neoplasia/patología , Quistes Odontogénicos/patología , Tumores Odontogénicos/metabolismo , Tumores Odontogénicos/patología , Quiste Radicular/patologíaRESUMEN
BACKGROUND AND OBJECTIVE: Reduced expression of syndecan-1 (CD138), increased proliferation index, and modifications in the expression of the molecular RANK/RANKL/OPG triad are related to an intensified potential of aggressiveness and invasion of diverse tumors and cysts. The aim was to compare the expression of Ki-67, CD138, and the molecular triad RANK, RANKL, and OPG in odontogenic keratocysts (OKC), unicystic ameloblastomas (UA), and dentigerous cysts (DC). METHODS: Immunohistochemistry for Ki-67, CD138, RANK, RANKL, and OPG was performed in 58 odontogenic cystic lesions (22 OKC, 17 DC, and 19 UA). RESULTS: A higher expression of Ki-67 was identified in OKC as compared to UA (p < 0.0001). UA exhibited a greater loss of CD138 expression versus OKCs (p > 0.0034). RANKL was expressed higher in the epithelium (p = 0.0002) and in the stroma (p = 0.0004) of UA. DC had a lower expression of these markers. CONCLUSION: Higher RANKL expression together with the reduction on CD138 expression in UA could be linked to a greater invasive and destructive potential, while the increased proliferation rate observed in OKC could be related to its continuous intrabony growth. The expansion of DC does not seem to be related to such factors, justifying the different therapeutic approaches proposed for each of these entities.
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Ameloblastoma/metabolismo , Biomarcadores/metabolismo , Quiste Dentígero/metabolismo , Neoplasias Maxilomandibulares/metabolismo , Quistes Odontogénicos/metabolismo , Regulación de la Expresión Génica , Humanos , Antígeno Ki-67/metabolismo , Osteoprotegerina/metabolismo , Ligando RANK/metabolismo , Receptor Activador del Factor Nuclear kappa-B/metabolismo , Sindecano-1/metabolismoRESUMEN
Benign epithelial odontogenic lesions are great clinical importance entities that develop in the jaws from the tissues that form teeth. It has been shown that benign and malignant tumors are present in a large number of tumor stem cells, which has great implications in the development of these lesions. Oct-4 and CD44 have been demonstrated as important markers for tumoral stem cells. The aim of this study was investigate the presence of stem cell markers Oct-4 and CD44 in benign epithelial odontogenic lesions. Twenty odontogenic keratocysts (OKC), 20 ameloblastomas (AMB) of the solid/multicystic type and 20 adenomatoid odontogenic tumors (AOT) were retrospectively analyzed for immunohistochemical detection of Oct-4 and CD44 in their epithelial component. All cases were positive for the two markers, with the majority exhibiting a high expression. Analysis of the expression of Oct-4 revealed no statistically significant differences (p = 0.406) between the lesions studied. Regarding CD44, there was a significant difference between the cases of AMB and AOT in relation with OKC, with the latter presenting a greater labelling (p = 0.034). No statistically significant correlation between Oct-4 and CD44 was observed in the lesions. In our findings, the presence of stem cell-like phenotype at various sites of the epithelial component of the odontogenic lesions was identified, suggesting its possible participation in histogenesis and differentiation without, however, exerting influence on the aggressiveness of the lesions.
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Quiste Dentígero/metabolismo , Células Epiteliales/metabolismo , Receptores de Hialuranos/metabolismo , Neoplasias Maxilomandibulares/metabolismo , Factor 3 de Transcripción de Unión a Octámeros/metabolismo , Quiste Dentígero/patología , Células Epiteliales/patología , Humanos , Neoplasias Maxilomandibulares/patología , Estudios RetrospectivosRESUMEN
CDC7 is a serine/threonine kinase which has an essential role in initiation of DNA proliferation and S phase. It increases the invasion and proliferation in many pathologic lesions. This study aimed to evaluate the expression of CDC7 in the most common odontogenic cysts. We evaluated 17 dentigerous cysts, 18 odontogenic keratocysts (OKC) and 13 radicular cysts immunohistochemically. The mean expression of CDC7 was analyzed using ANOVA and Post-HOC methods. All specimens revealed CDC7 expression. Higher expression of CDC7 in OKC and radicular cyst was shown in comparison to dentigerous cyst (P < 0.001), while radicular cyst and OKC groups showed no difference in CDC7 expression (P = 0.738). The high expression of CDC7 in OKC suggests that this protein could be related to the higher proliferation rate and invasiveness of OKC. On the other hand, the higher CDC7 expression in radicular cyst may simply be related to inflammation as this cyst is neither aggressive nor invasive.
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Proteínas de Ciclo Celular/metabolismo , Quiste Dentígero/metabolismo , Quistes Odontogénicos/metabolismo , Proteínas Serina-Treonina Quinasas/metabolismo , Quiste Radicular/metabolismo , Adolescente , Adulto , Femenino , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
The aim of this study was to examine the level and basic characteristics of cellderived microparticles (MPs) in the cyst fluids of odontogenic keratocysts (OKCs). For this purpose, MPs from the cyst fluids (CFMPs) of OKCs were purified by a classic differential centrifugation method and characterized by a transmission electron microscope and fluorescence microscope. Flow cytometric analysis was used to determine the size, concentration and cellular origins of the CFMPs. Moreover, the expression level of receptor activator for nuclear factorκB ligand in the OKCs was evaluated by immunohistochemical staining and then analyzed for its correlation with the concentration of CFMPs by Spearman's rank correlation test. In addition, reverse transcriptionquantitative polymerase chain reaction (RTqPCR) and tartaricresistant acid phosphatase (TRAP) staining were performed to examine the osteoclastogenesis of mouse bone marrowderived macrophages (BMMs) in response to CFMPs. The results revealed that the levels of total CFMPs were significantly elevated in OKCs compared with dentigerous cysts (DCs) and radicular cysts (RCs). In addition, in vitro experiments further revealed that CFMPs derived from the OKCs of patients could be taken up by BMMs, leading to a significant increase in the mRNA expression levels of nuclear factor of activated Tcells 1 (NFATc1) and TRAP. Moreover, TRAPpositive multinucleated osteoclasts were successfully cultured in the presence of macrophage colonystimulating factor (MCSF) and CFMPs with BMMs. On the whole, our findings indicate that patients with OKCs have higher levels of CFMPs compared with patients with DCs and RCs, which may be associated with the bone resorption of OKCs.
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Micropartículas Derivadas de Células/metabolismo , Quiste Dentígero/metabolismo , FN-kappa B/metabolismo , Factores de Transcripción NFATC/genética , Fosfatasa Ácida Tartratorresistente/genética , Adolescente , Adulto , Anciano , Animales , Micropartículas Derivadas de Células/genética , Células Cultivadas , Niño , Líquido Quístico/citología , Quiste Dentígero/genética , Femenino , Humanos , Macrófagos/citología , Masculino , Ratones , Microscopía Electrónica de Transmisión , Persona de Mediana Edad , Quistes Odontogénicos/genética , Quistes Odontogénicos/metabolismo , Adulto JovenRESUMEN
INTRODUCTION: Odontogenic cysts are commonly encountered lesions among head and neck pathologies. Odontogenic keratocyst (OKC) has unique features of recurrence and local aggressiveness. Podoplanin (PDP) is a lymphatic endothelial marker and is shown to be expressed in a variety of tissues. Hence, we planned to assess the significance of PDP in OKC and dentigerous cyst (DC). MATERIALS AND METHODS: The present study included assessment of immunoexpression of PDP in OKC and DC. Twenty specimens each of OKC and DC were included in the present study and were stained with D2-40 antibody. All the sections were analyzed and were categorized as negative staining, weakly positive staining, and strongly positive staining. All the results were analyzed by Statistical Package for the Social Sciences (SPSS) software. RESULTS: We detected PDP-positive staining in the cell membrane and cytoplasm of the cells of basal cell layer and supra-basal cell layers. In DC cases, we observed positive staining only in cases associated with inflammation. CONCLUSION: Podoplanin does play a significant role in enhancing the local invasive and neoplastic properties of OKC. CLINICAL SIGNIFICANCE: Podoplanin expression in OKC is potentially associated with moderate invasive nature of the neighboring structures.
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Quiste Dentígero/metabolismo , Enfermedades Maxilomandibulares/metabolismo , Glicoproteínas de Membrana/metabolismo , Quistes Odontogénicos/metabolismo , Biomarcadores/metabolismo , Membrana Celular/metabolismo , Proliferación Celular , Citoplasma/metabolismo , Humanos , InmunohistoquímicaRESUMEN
INTRODUCTION: An array of odontogenic lesions manifest in the maxillofacial region with variable presentations. The biological behavior of lesions, such as odontogenic keratocyst (OKC), dentigerous cyst (DC), and ameloblastoma (AM) always invite debate. Glucose transporter 1 (GLUT-1) is proven to be an indicator of metabolic behavior of several benign and malignant neoplasms. AIM: The purpose of this study was to evaluate the expression of GLUT-1 in OKC, DC, and AM to understand their metabolic behavior. MATERIALS AND METHODS: Immunohistochemical expression of GLUT-1 was evaluated in each of the 15 cases of OKC, DC, and AM. The number of labeled cells, staining intensity, and membrane or cytoplasmic expressions were the parameters assessed and analyzed using chi-square test. RESULTS: All cases showed positive GLUT-1 expression: 86.6% OKC showed more than 50% labeled cells followed by DC (40%) and AM (26.5%); 53.3% OKC showed strong intensity in comparison to AM, which showed weak intensity in 53.3% cases; 86.6% of OKCs showed both membrane and cytoplasmic expression followed by DC (40%) and AM (26.6%), whereas 73.3% of AM showed only membrane expression followed by DC (60%) and OKC (13.3%). CONCLUSION: Odontogenic keratocyst was found out to be more metabolically active followed by DC and AM.
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Ameloblastoma/metabolismo , Transportador de Glucosa de Tipo 1/metabolismo , Neoplasias Maxilomandibulares/metabolismo , Quistes Odontogénicos/metabolismo , Quiste Dentígero/metabolismo , HumanosRESUMEN
BACKGROUND: Benign epithelial odontogenic tumors such as ameloblastoma and keratocystic odontogenic tumor (KCOT) may exhibit an aggressive clinical course reminiscent of malignancies. Recent studies have indicated that astrocyte elevated gene-1 (AEG-1) is highly expressed in a variety of malignant neoplasms and its overexpression is associated with tumor invasion, metastasis, and poor survival. However, the role of AEG-1 in odontogenic tumors and cysts is still undiscovered. METHODS: Immunohistochemical staining of AEG-1 was performed in 42 cases of ameloblastoma, 29 cases of KCOT, and 19 cases of dentigerous cyst. Correlations between AEG-1 expression and clinical parameters of ameloblastomas or KCOTs were statistically analyzed. RESULTS: AEG-1-positive staining was found in 37 (88%) of 42 ameloblastomas and in 24 (83%) of 29 KCOTs. None of 19 dentigerous cysts were positive for AEG-1 protein. For ameloblastomas, AEG-1 protein expression was significantly higher in ameloblast-like cells than in stellate reticulum-like cells (P = 0.003). For KCOTs, AEG-1 protein was diffusely expressed in all lining epithelial cells except the superficial parakeratinized cells. Moreover, the frequency of cortical plate perforation was significantly higher in ameloblastomas with high AEG-1 expression than in ameloblastomas with low or negative AEG-1 expression (P = 0.043). CONCLUSION: Significantly higher expression of AEG-1 protein in ameloblastomas and KCOTs than in dentigerous cysts and significantly greater frequency of cortical plate perforation in high AEG-1-expressed ameloblastomas than in low or negative AEG-1-expressed ameloblastomas may imply the high potential of AEG-1 to serve as a locally invasive biomarker and a target for novel therapy.
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Ameloblastoma/metabolismo , Biomarcadores de Tumor/metabolismo , Moléculas de Adhesión Celular/metabolismo , Quiste Dentígero/metabolismo , Tumores Odontogénicos/metabolismo , Humanos , Inmunohistoquímica , Proteínas de la Membrana , Proteínas de Unión al ARNRESUMEN
BACKGROUND: The number of studies investigating the immunohistochemical characteristics of glandular odontogenic cysts (GOCs) is limited, due to its rarity. TGF-beta has been suggested to induce podoplanin expression in some lesions. We aimed to evaluate and compare podoplanin and TGF-beta expression in GOC and other odontogenic cystic lesions. METHODS: A total of 43 samples including five GOCs, 10 dentigerous cysts (DCs), eight unicystic ameloblastoma (UAs), and 20 radicular cysts (RCs) were selected and subjected to immunohistochemical staining using monoclonal antibodies against podoplanin and TGF-beta. Kruskal-Wallis test and Mann-Whitney U-test were used for statistical analysis along with Bonferroni for adjusting P-values (P < 0.05). RESULTS: Podoplanin immunoreactivity was observed in 80%, 70%, and 100% of DCs, RCs, and UAs, respectively, while none of the GOCs were positive for this marker (P = 0.004). Significant differences were only found in the GOC specimens. TGF-beta positivity occurred in the capsule and epithelium of all GOCs and DCs, while RCs and UAs demonstrated different expression percentages in the capsular and epithelial tissues. Epithelial TGF-beta showed significant differences among the studied lesions (P = 0.007) with the main difference found between DCs with RCs and DCs with UAs. CONCLUSIONS: Lack of podoplanin expression might be involved in the characteristic histologic and behavioral features of GOC, which seems to be unrelated to TGF-beta expression.
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Enfermedades Maxilomandibulares/metabolismo , Glicoproteínas de Membrana/metabolismo , Quistes Odontogénicos/metabolismo , Factor de Crecimiento Transformador beta/metabolismo , Ameloblastoma/metabolismo , Ameloblastoma/patología , Quiste Dentígero/metabolismo , Quiste Dentígero/patología , Humanos , Neoplasias Maxilomandibulares/metabolismo , Quistes Odontogénicos/patología , Quiste Radicular/metabolismo , Quiste Radicular/patologíaRESUMEN
UNLABELLED: The aim of this study is to analyze the immunoexpression of Ki67, p53, MCM3 and PCNA markers in epithelial remnants of dental follicles of impacted teeth and to identify a possible correlation between the immunoexpression of these markers in dentigerous cysts and keratocystic odontogenic tumors in order to evaluate their evolutionary behavior. MATERIALS AND METHODS: A total of 102 cases were included in the study and divided into three subgroups: the first subgroup consisted of 62 cases with dental follicles of impacted teeth, the second included 20 cases of dentigerous cysts and the third subgroup comprised a number of 20 cases with keratocystic odontogenic tumors. Immunomarking with the four antibodies was performed. RESULTS: A positive marking was obtained in over 60% of the dental follicles for all markers. Statistically significant differences were also obtained in dentigerous cysts and keratocystic odontogenic tumors for Ki67, p53 and MCM3. Assessment of the four antibodies in the two layers of keratocystic odontogenic tumors shows a positive correlation between Ki67 and MCM3 both for the basal and parabasal layer, with slightly increased values in the latter. CONCLUSIONS: In order to determine the proliferative capacity of epithelial remnants in the dental follicles, Ki67 and PCNA, Ki67 and MCM3 are the most useful markers in practice; they have similar behavior and are more likely to help in distinguishing between dentigerous cysts and keratocystic odontogenic tumors.
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Saco Dental/metabolismo , Quiste Dentígero/metabolismo , Antígeno Ki-67/metabolismo , Componente 3 del Complejo de Mantenimiento de Minicromosoma/metabolismo , Tumores Odontogénicos/metabolismo , Antígeno Nuclear de Célula en Proliferación/metabolismo , Diente Impactado/metabolismo , Proteína p53 Supresora de Tumor/metabolismo , Saco Dental/patología , Quiste Dentígero/patología , Humanos , Inmunohistoquímica , Quistes Odontogénicos/metabolismo , Quistes Odontogénicos/patología , Tumores Odontogénicos/patología , Diente Impactado/patologíaRESUMEN
BACKGROUND: Some benign odontogenic lesions have a distinct biological behavior with high recurrence rates and local aggressive behavior. To determine whether glucose transporters proteins (GLUT-1 and GLUT-3) and carbonic anhydrase IX (CA IX) are associated with the development of as dentigerous cyst (DC), odontogenic keratocyst (OK), and ameloblastoma (AM), we evaluated the immunohistochemical expression of these proteins in these lesions. MATERIALS AND METHODS: Immunoexpression of GLUT-1, GLUT-3, and CA IX was evaluated semiquantitative fields in each of the 20 cases of OK, AM, and DC. The cases were classified according to the scores: 0 (0% positive cells), 1 (<10% of positive cells), 2 (10-50% of positive cells), and 3 (>50% of positive cells). The statistical analysis was performed using Pearson's chi-square, Kruskal-Wallis and Mann-Whitney tests. RESULTS: All cases were positive for GLUT-1 and 65% of OK showed scored 3. Staining was diffuse in 90% of OK and 85% of DC cases (P < 0.001). In 50% of OK and AM, staining was only observed in the membrane (P = 0.01). Most of the samples (66.7%) were negative for GLUT-3. Staining intensity for anhydrase was higher in the epithelium of DC when compared to OK (P = 0.01). Strong staining was observed in 55% of DC and 20% of OK samples (P = 0.01). CONCLUSIONS: These results suggest that GLUT-1 may be involved in the metabolic regulation of glucose in odontogenic lesions studied. In addition, CA IX appears to influence the development of AM, OK, and DC which can explain the differences their biological behavior.
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Ameloblastoma/metabolismo , Anhidrasa Carbónica IX/metabolismo , Quiste Dentígero/metabolismo , Transportador de Glucosa de Tipo 1/metabolismo , Transportador de Glucosa de Tipo 3/metabolismo , Neoplasias Maxilomandibulares/metabolismo , Quistes Odontogénicos/metabolismo , Biomarcadores de Tumor/metabolismo , Humanos , InmunohistoquímicaRESUMEN
The aims of this study were to determine the presence and distribution of vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor-2 (VEGFR2) in dentigerous cysts compared with normal dental follicles as a control tissue and to evaluate endothelial cells and proliferating cells as indicators of angiogenic activity in these tissues.Twenty specimens histologically diagnosed as dentigerous cysts and 20 dental follicle specimens were included. Immunohistochemistry (IHC) using anti-VEGF and anti-VEGFR2 antibodies stained for the growth factor and its receptor, while anti-CD34 and anti-CD146 antibodies were used to identify endothelial cells. Anti-proliferating cell nuclear antigen (PCNA) antibody detected proliferating cells within the specimens. Slides were examined microscopically and results evaluated using kappa statistics, negative binomial regression and ordinal logistic regression.The mean age for patients with dentigerous cysts was 23 years and they were more common in males. Proteins for VEGF, VEGFR2, PCNA, CD34, and CD146 were expressed in all dentigerous cysts and dental follicles. VEGF and VEGFR2 were expressed on several cell types within the tissues, however there was a significantly greater percentage of positive staining in dentigerous cysts compared with dental follicles (odds ratioâ=â31.24, pâ<â0.001). CD34(+), CD146(+), and PCNA(+) cells were observed in both dentigerous cysts and dental follicles but for all markers there were significantly more positive cells in dentigerous cysts (pâ<â0.001); this was especially evident in cases associated with inflammation. PCNA was seen in most endothelial cells lining small thin walled blood vessels suggesting endothelial proliferation. There was a high level of intra- and inter-examiner agreement (kappa 0.77 and 0.75, respectively).VEGF and VEGFR2 and angiogenic activity are present in dental follicles and dentigerous cysts and may contribute to local bone resorption for tooth eruption or the development and progression of dentigerous cysts.
Asunto(s)
Quiste Dentígero/metabolismo , Células Endoteliales/metabolismo , Tercer Molar/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo , Receptor 2 de Factores de Crecimiento Endotelial Vascular/metabolismo , Adolescente , Adulto , Proliferación Celular/fisiología , Quiste Dentígero/patología , Femenino , Humanos , Inmunohistoquímica/métodos , Inflamación/patología , Masculino , Neovascularización Patológica/patología , Adulto JovenRESUMEN
OBJECTIVE: Benign and malignant tumor cells can express altered adhesion properties, and these features can be associated with their proliferative and invasive characteristics. This study aimed to evaluate syndecan-1 and Ki-67 expression in ghost cell-containing odontogenic tumors. STUDY DESIGN: Clinical data were retrieved from laboratory records, and hematoxylin-eosin-stained slides and sections, labeled with monoclonal antibodies anti-syndecan-1 and anti-Ki-67 using the immunoperoxidase technique, were evaluated. RESULTS: Included were 21 central calcifying cystic odontogenic tumors (CCOTs) (4 associated with odontoma), 2 peripheral CCOTs, 1 dentinogenic ghost cell tumor, and 1 ghost cell odontogenic carcinoma (GCOC). Syndecan-1 was mainly expressed in cells resembling stellate reticulum and in stromal cells from the fibrous capsule. The mean Ki-67 labeling index was 4.1% (49.3% for GCOC), but it was not associated with syndecan-1 expression. CONCLUSIONS: Syndecan-1 is variably expressed in cells resembling the stellate reticulum, stromal cells, and basal cells and might be associated with the biology of these tumors.
Asunto(s)
Neoplasias Maxilomandibulares/metabolismo , Antígeno Ki-67/metabolismo , Quistes Odontogénicos/metabolismo , Tumores Odontogénicos/metabolismo , Sindecano-1/metabolismo , Adolescente , Adulto , Biomarcadores de Tumor/metabolismo , Quiste Dentígero/metabolismo , Quiste Dentígero/patología , Femenino , Humanos , Técnicas para Inmunoenzimas , Neoplasias Maxilomandibulares/patología , Masculino , Quiste Odontogénico Calcificado/metabolismo , Quiste Odontogénico Calcificado/patología , Quistes Odontogénicos/patología , Tumores Odontogénicos/patologíaRESUMEN
The epithelial lining of odontogenic keratocysts exhibits either parakeratosis or orthokeratosis. In 2005, the WHO classified odontogenic keratocysts with parakeratosis as keratocystic odontogenic tumors (KCOT). Odontogenic keratocysts with orthokeratosis were not classified as odontogenic tumors, but instead referred to as orthokeratinized odontogenic cysts (OOC). To clarify the difference between these two lesions, we investigated their biological characteristics using immunohistochemical studies for cytokeratins (CK) in KCOT and OOC as well as in dentigerous cysts (DC), radicular cysts (RC) and dermoid cysts (DMC). We examined twenty-five cases of KCOT, fifteen cases each of OOC, DC and RC, and ten cases of DMC. We studied the immunohistochemical expression of CK10, 13, 17 and 19. To evaluate the immunohistochemical staining pattern, we divided the epithelial lining of the lesions into three layers (surface layer: su, spinous layer: sp, basal layer: ba). For CK10, most OOC and DMC specimens of su and sp were positive. For CK13 and 19, most KCOT, DC and RC specimens of su and sp were positive. For CK17, most KCOT specimens of su and sp were positive. The percentages of total CK expression of su and sp, and ba of CK19 differed significantly between the lesions (P < 0.001). These results support the hypothesis that OOC originate from not the odontogenic apparatus, but the oral epithelial component.