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Medicina Oral, Patologia Oral Y Cirugia... Jul 2020Phosphatase and tensin homolog (PTEN) acts as a tumor suppressor gene. Inactivation of PTEN has been reported in various types of cancers. PTEN promoter methylation...
BACKGROUND
Phosphatase and tensin homolog (PTEN) acts as a tumor suppressor gene. Inactivation of PTEN has been reported in various types of cancers. PTEN promoter methylation possibly underlies PTEN inactivation, which results in tumorigenesis. The aim of this study was to investigate whether PTEN promoter methylation contributes to PTEN inactivation in ameloblastoma and its associated protein expression.
MATERIAL AND METHODS
In total, 20 fresh-frozen ameloblastoma samples were evaluated for PTEN promoter methylation using methylation-specific polymerase chain reaction (MS-PCR). A subset of 10 paraffin-embedded ameloblastoma samples was examined for PTEN expression through immunohistochemistry. Four primary cultured ameloblastoma cells were investigated for PTEN promoter methylation and PTEN transcriptional expression via reverse transcription PCR.
RESULTS
PTEN promoter methylation was detected in 65% (13/20) of the ameloblastoma samples. Of 10 ameloblastoma samples, 4 exhibited reduced PTEN expression. Of 5 samples with methylated PTEN, 3 (60%) were associated with loss of PTEN expression. However, PTEN expression was detected in 4 (80%) of 5 samples with unmethylated PTEN. In addition, 3 (75%) of 4 primary ameloblastoma cell cultures exhibited an inverse correlation between PTEN promoter methylation and PTEN transcription level.
CONCLUSIONS
PTEN promoter methylation is found in a number of ameloblastomas but not significantly correlated with loss of PTEN expression. Genetic or epigenetic mechanisms other than PTEN promoter methylation may contribute to PTEN inactivation in ameloblastoma tumor cells.
Topics: Ameloblastoma; DNA Methylation; Humans; Immunohistochemistry; PTEN Phosphohydrolase; Polymerase Chain Reaction; Promoter Regions, Genetic
PubMed: 32134893
DOI: 10.4317/medoral.23498 -
Laboratory Investigation; a Journal of... Jan 2022Ameloblastoma (AB) is the most common benign epithelial odontogenic tumor occurring in the jawbone. AB is a slowly growing tumor but sometimes shows a locally invasive...
Ameloblastoma (AB) is the most common benign epithelial odontogenic tumor occurring in the jawbone. AB is a slowly growing tumor but sometimes shows a locally invasive and an aggressive growth pattern with a marked bone resorption. In addition, the local recurrence and distant metastasis of AB also sometimes occurs, which resembles one of the typical malignant potentials. From these points of view, to understand better the mechanisms of AB cell migration or invasion is necessary for the better clinical therapy and improvements of the patients' quality of life. Microtubules in eukaryotic cells reveal the shape of hollow cylinders made up of polymerized alpha (α)- and beta (β)-tubulin dimers and form the cytoskeleton together with microfilaments and intermediate filaments. Microtubules play important roles in cell migration by undergoing assembly and disassembly with post-translational modifications. Stability of microtubules caused by their acetylation is involved in cell migration. In this study, we investigated the expression and distribution of acetylated α-tubulin and alpha-tubulin N-acetyltransferase 1 (αTAT1), an enzyme which acetylates Lys-40 in α-tubulin, in AB specimens, and analyzed how tubulin was acetylated by αTAT1 activation in a human AB cell line, AM-1. Finally, we clarified that TGF-β-activated kinase1 (TAK1) was phosphorylated by TGF-β stimulation, then, induced tubulin acetylation via αTAT1 activation, which subsequently activated the migration and invasion of AB cells.
Topics: Acetylation; Acetyltransferases; Adolescent; Adult; Aged; Ameloblastoma; Cell Line, Tumor; Cell Movement; Female; Humans; Immunohistochemistry; Jaw Neoplasms; MAP Kinase Kinase Kinases; Male; Microtubule Proteins; Middle Aged; Neoplasm Invasiveness; RNA Interference; Transforming Growth Factor beta; Tubulin; Young Adult
PubMed: 34508164
DOI: 10.1038/s41374-021-00671-w -
Journal of Oral and Maxillofacial... 2023The purpose of this experimental study was to evaluate and compare the degree of expression of Wilm's Tumor Gene-1 (WT-1), Syndecan (CD 138) and Snail in Ameloblastoma...
BACKGROUND
The purpose of this experimental study was to evaluate and compare the degree of expression of Wilm's Tumor Gene-1 (WT-1), Syndecan (CD 138) and Snail in Ameloblastoma and odontogenic keratocyst (OKC) and to analyse their potential role in pathogenesis.
METHODS AND MATERIAL
Immunohistochemical analysis was performed to evaluate WT-1, Syndecan and Snail expression in Ameloblastoma ( = 20) and OKC ( = 20). Topographical immunoexpression pattern of Ameloblast-like cells, Stellate Reticulum-like cells in Ameloblastoma and basal layer as well as suprabasal layer of cells of OKC were also compared. The results obtained were subjected to ANOVA test and Tukey HSD test through SPSS software 20.0 for Microsoft Windows.
RESULTS
WT-1 and Snail overexpression was seen in both Ameloblastoma and OKCs. Syndecan, responsible for maintaining normal cellular morphology, cell-cell adhesion and differentiation was significantly downregulated in both the lesions. The Ameloblasts-like cells and the basal cells showed significantly higher immunopositivity for WT-1 and Syndecan as compared to that of basal cells. An inverse relation was noted for Snail protein. The ANOVA test predicted a statistically significant difference of expression across the lesions with a value <0.0001 for Syndecan and Snail.
CONCLUSIONS
The under-expression of epithelial membrane protein Syndecan-1 and upregulation of EMT transcription factor Snail can promote local invasion and is indicative of poor prognosis of these lesions. The overexpression of WT-1 results in tumorigenesis, proliferation and localized aggressiveness of Ameloblastoma and intrabony growth of OKC. Further investigation on the biologic behaviour of OKC is still recommended to arrive at more specific conclusions regarding its nature.
PubMed: 37854929
DOI: 10.4103/jomfp.jomfp_301_22 -
Journal of Oral and Maxillofacial... 2019Odontogenesis is a highly coordinated and complex process which depends on cell-cell interactions that result in initiation and generation of tooth. Tissue remnants of...
BACKGROUND
Odontogenesis is a highly coordinated and complex process which depends on cell-cell interactions that result in initiation and generation of tooth. Tissue remnants of developing tooth can form odontogenic tumors possibly, reflecting different developmental stages in tooth formation. In both odontogenesis and odontogenic tumors, stroma plays a prominent role in maintaining epithelial tissues with continuous molecular interactions. As the collagen forms an integral part of connective tissue stroma, in the present study, polarization colors and thickness of the collagen fibers were assessed in both tooth germ papillae and ameloblastoma using picrosirius red (PSR) stain.
MATERIALS AND METHODS
Collagen fibers in 20 cases of ameloblastoma and 10 tooth germs from the human fetus were evaluated with PSR stain and examined under polarizing microscopy.
RESULTS
Polarization colors of red-colored collagen fibers with greater diameter were more in ameloblastoma when compared to tooth germ papillae in which green-colored collagen fibers with smaller diameter being more.
CONCLUSION
The absence of hard tissue formation in ameloblastoma might be due to the presence of significantly more number and greater thickness of red-colored collagen fibers. Thus, the nature of collagen fibers can predict the nature in terms of biologic behavior and prognosis.
PubMed: 31942136
DOI: 10.4103/jomfp.JOMFP_204_17 -
Frontiers in Immunology 2023Ameloblastoma is a locally invasive and aggressive epithelial odontogenic neoplasm. The BRAF-V600E gene mutation is a prevalent genetic alteration found in this tumor...
BACKGROUND
Ameloblastoma is a locally invasive and aggressive epithelial odontogenic neoplasm. The BRAF-V600E gene mutation is a prevalent genetic alteration found in this tumor and is considered to have a crucial role in its pathogenesis. The objective of this study is to develop and validate a radiomics-based machine learning method for the identification of BRAF-V600E gene mutations in ameloblastoma patients.
METHODS
In this retrospective study, data from 103 patients diagnosed with ameloblastoma who underwent BRAF-V600E mutation testing were collected. Of these patients, 72 were included in the training cohort, while 31 were included in the validation cohort. To address class imbalance, synthetic minority over-sampling technique (SMOTE) is applied in our study. Radiomics features were extracted from preprocessed CT images, and the most relevant features, including both radiomics and clinical data, were selected for analysis. Machine learning methods were utilized to construct models. The performance of these models in distinguishing between patients with and without BRAF-V600E gene mutations was evaluated using the receiver operating characteristic (ROC) curve.
RESULTS
When the analysis was based on radiomics signature, Random Forest performed better than the others, with the area under the ROC curve (AUC) of 0.87 (95%CI, 0.68-1.00). The performance of XGBoost model is slightly lower than that of Random Forest, and its AUC is 0.83 (95% CI, 0.60-1.00). The nomogram evident that among younger women, the affected region primarily lies within the mandible, and patients with larger tumor diameters exhibit a heightened risk. Additionally, patients with higher radiomics signature scores are more susceptible to the BRAF-V600E gene mutations.
CONCLUSIONS
Our study presents a comprehensive radiomics-based machine learning model using five different methods to accurately detect BRAF-V600E gene mutations in patients diagnosed with ameloblastoma. The Random Forest model's high predictive performance, with AUC of 0.87, demonstrates its potential for facilitating a convenient and cost-effective way of identifying patients with the mutation without the need for invasive tumor sampling for molecular testing. This non-invasive approach has the potential to guide preoperative or postoperative drug treatment for affected individuals, thereby improving outcomes.
Topics: Humans; Female; Ameloblastoma; Proto-Oncogene Proteins B-raf; Retrospective Studies; Machine Learning; Mutation
PubMed: 37646022
DOI: 10.3389/fimmu.2023.1180908 -
Cell & Bioscience Sep 2022Transcriptome analysis has been known as a functional tool for cancer research recently. Mounting evidence indicated that calcium signaling plays several key roles in...
BACKGROUND
Transcriptome analysis has been known as a functional tool for cancer research recently. Mounting evidence indicated that calcium signaling plays several key roles in cancer progression. Despite numerous studies examining calcium signaling in cancer, calcium signaling studies in ameloblastoma are limited.
RESULTS
In the present study, comparative transcriptome profiling of two representative odontogenic lesions, ameloblastoma and odontogenic keratocyst, revealed that Cav1.2 (CACNA1C, an L-type voltage-gated calcium channel) is strongly enriched in ameloblastoma. It was confirmed that the Ca influx in ameloblastoma cells is mainly mediated by Cav1.2 through L-type voltage-gated calcium channel agonist and blocking reagent treatment. Overexpression and knockdown of Cav1.2 showed that Cav1.2 is directly involved in the regulation of the nuclear translocation of nuclear factor of activated T cell 1 (NFATc1), which causes cell proliferation. Furthermore, a tumoroid study indicated that Cav1.2-dependent Ca entry is also associated with the maintenance of stemness of ameloblastoma cells via the enhancement of Wnt/β-catenin signaling activity.
CONCLUSION
In conclusion, Cav1.2 regulates the NFATc1 nuclear translocation to enhance ameloblastoma cell proliferation. Furthermore, Cav1.2 dependent Ca influx contributes to the Wnt/β-catenin activity for the ameloblastoma cell stemness and tumorigenicity. Our fundamental findings could have a major impact in the fields of oral maxillofacial surgery, and genetic manipulation or pharmacological approaches to Cav1.2 can be considered as new therapeutic options.
PubMed: 36057617
DOI: 10.1186/s13578-022-00873-9 -
Head and Neck Pathology Dec 2020Peripheral ameloblastoma (PA) is a prototype form of extraosseous odontogenic tumor. As knowledge of PA has accumulated on the basis of more than 200 cases reported... (Review)
Review
Peripheral ameloblastoma (PA) is a prototype form of extraosseous odontogenic tumor. As knowledge of PA has accumulated on the basis of more than 200 cases reported worldwide over a 60-year timeframe, it is important to comprehend the historical evolution of this entity. In 2018, we summarized the American history of PA, stressing the important early strides made by Bloodgood in 1904 with his many original observations of the "epulis form of ameloblastoma". During the preparation of our previous report, we were able to find several earlier and interesting descriptions in the literature. This review covers the early history of PA since the nineteenth century, chronologically focusing on meritorious articles published in the United States and Europe.
Topics: Ameloblastoma; History, 19th Century; History, 20th Century; History, 21st Century; Humans
PubMed: 32451874
DOI: 10.1007/s12105-020-01168-6 -
Journal of Maxillofacial and Oral... Sep 2019The purpose of the article is to review 45 cases of ameloblastoma treated in a tertiary care centre depending on the extent of the pathology, in terms of recurrence and...
PURPOSE
The purpose of the article is to review 45 cases of ameloblastoma treated in a tertiary care centre depending on the extent of the pathology, in terms of recurrence and morbidity of the patients.
MATERIALS AND METHOD
This was a retrospective study of patients who underwent treatment for ameloblastoma between 2009 and 2018 at Vydehi Institute of Dental Sciences, Bangalore. During the first phase of 4 years, the focus of the treatment was on avoiding any recurrence, and therefore, resection followed by reconstruction with reconstruction plates was the only modality used in ten patients. However, from 2014, it was decided to treat each patient based on the extent of the lesion and decide on either conservative management in the form of enucleation followed by peripheral ostectomy and chemical cauterisation or resection with safe margins and reconstruction with reconstruction plates.
RESULTS
The study sample consisted of 45 patients, and the ages ranged from 12 to 65 years with an average of 36. There were 30 males and 15 females. In the first phase of treatment protocol adopted, ten patients underwent resection. In the later period, 18 patients were treated by conservative methods and 16 patients were treated by radical management. There were only three recurrences over a period of 3-year follow-up in the group treated conservatively.
CONCLUSION
Considering the benign nature of the tumour and the morbidity after resection, patients, most of whom are in the younger age group, can still be subjected to conservative treatment provided they are followed up for a long period thus assuring them of a better quality of life.
PubMed: 31371882
DOI: 10.1007/s12663-019-01189-x -
Frequency of Odontogenic Tumors: A Single Center Study of 1089 Cases in Japan and Literature Review.Head and Neck Pathology Jun 2022Several attempts have been made to classify odontogenic tumors; however, the need for a uniform international classification system led the World Health Organization... (Review)
Review
Several attempts have been made to classify odontogenic tumors; however, the need for a uniform international classification system led the World Health Organization (WHO) to present a classification of odontogenic tumors in 1971. We aimed to evaluate the number and types of odontogenic tumors examined at the Tokyo Dental College Hospital in Japan to determine the frequency and types of odontogenic tumors, based on the 2017 WHO classification system, as this information has not been reported previously in Japan. We also compared the results of our evaluation with those reported in previous studies. We conducted a clinicopathological evaluation of odontogenic tumors examined at the Tokyo Dental College Hospital between 1975 and 2020. This included an analysis of 1089 cases (malignant, n = 10, 0.9%; benign, n = 1079, 99.1%) based on the 2017 World Health Organization Classification of Head and Neck Tumors. We identified 483 (44.3%), 487 (44.7%), and 109 (10.0%) benign epithelial odontogenic, mixed odontogenic, and mesenchymal tumors, respectively. The most common tumor types were odontoma (42.5%) and ameloblastoma (41.9%). Of the 1089 cases, 585 (53.7%) and 504 (46.3%) were male and female patients, respectively. Ameloblastoma and ameloblastic fibroma occurred more commonly in male patients, whereas odontogenic fibroma and cemento-ossifying fibroma affected female patients primarily. The age at diagnosis ranged from three to 87 (mean, 29.05) years. In 319 (29.3%) patients, the age at diagnosis ranged from 10 to 19 years. Ameloblastoma and odontoma were the most common tumor types among patients in their 20s and those aged 10-19 years, respectively. In 737 (67.7%) and 726 (66.7%) patients, the tumors were located in the mandible and posterior region, respectively. Ameloblastoma was particularly prevalent in the posterior mandible. Odontogenic tumors are rare lesions and appear to show a definite geographic variation.
Topics: Ameloblastoma; Female; Fibroma, Ossifying; Humans; Japan; Male; Odontogenic Tumors; Odontoma; Retrospective Studies
PubMed: 34716904
DOI: 10.1007/s12105-021-01390-w -
Case Reports in Dentistry 2022Intraosseous unicystic ameloblastoma (UA) is a rare subtype of a true neoplasm of odontogenic epithelial origin: ameloblastoma. Despite its rareness, dealing with UA is...
Intraosseous unicystic ameloblastoma (UA) is a rare subtype of a true neoplasm of odontogenic epithelial origin: ameloblastoma. Despite its rareness, dealing with UA is problematic. It is usually mistaken for an odontogenic cyst, and biopsy is rarely relevant because of its multiple growth patterns. The biggest challenge remains the treatment choice. When we are faced with a mural UA presenting strong similarities with a lateral periodontal cyst and having high rates of recurrence, how is the balance found between the young age, psychological fragility, postoperative process, and need for diagnostic biopsy? That was our dilemma. Our patient is a 23-year-old man with a mural unicystic ameloblastoma, diagnosed with general anxiety disorder. The final decision was to turn to a simple enucleation because of the small size of the lesion, and its radiological features strongly evoked a lateral periodontal cyst. Besides, his young age, psychological condition, and UA's proximity to the surrounding soft tissues guided us toward simple enucleation. Two years later, no sign of radiological recurrence was noted. However, we are aware of a later possibility of resection in case of recurrence.
PubMed: 35198251
DOI: 10.1155/2022/8197837