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Cancer Medicine Dec 2019Ameloblastic carcinoma (AC) is defined as a rare primary epithelial odontogenic malignant neoplasm and the malignant counterpart of benign epithelial odontogenic tumor...
Ameloblastic carcinoma (AC) is defined as a rare primary epithelial odontogenic malignant neoplasm and the malignant counterpart of benign epithelial odontogenic tumor of ameloblastoma (AB) by the WHO classification. AC develops pulmonary metastasis in about one third of the patients and reveals a poor prognosis. However, the mechanisms of AC oncogenesis remain unclear. In this report, we aimed to clarify the mechanisms of malignant transformation of AB or AC carcinogenesis. The relatively important genes in the malignant transformation of AB were screened by DNA microarray analysis, and the expression and localization of related proteins were examined by immunohistochemistry using samples of AB and secondary AC. Two genes of hypoxia-inducible factor 1 alpha subunit (HIF1A) and zinc finger E-box-binding homeobox 1 (ZEB1) were significantly and relatively upregulated in AC than in AB. Both genes were closely related in hypoxia and epithelial-mesenchymal transition (EMT). In addition, expressions of HIF-1α and ZEB1 proteins were significantly stronger in AC than in AB. In the cell assays using ameloblastoma cell line, AM-1, hypoxia condition upregulated the expression of transforming growth factor-β (TGF-β) and induced EMT. Furthermore, the hypoxia-induced morphological change and cell migration ability were inhibited by an antiallergic medicine tranilast. Finally, we concluded that hypoxia-induced HIF-1α and ZEB1 were critical for the malignant transformation of AB via TGF-β-dependent EMT. Then, both HIF-1α and ZEB1 could be potential biomarkers to predict the malignant transformation of AB.
Topics: Adolescent; Adult; Aged; Ameloblastoma; Cell Line, Tumor; Cell Transformation, Neoplastic; Epithelial-Mesenchymal Transition; Female; Gene Expression Profiling; Humans; Hypoxia; Hypoxia-Inducible Factor 1, alpha Subunit; Immunohistochemistry; Male; Middle Aged; Transforming Growth Factor beta; Young Adult; Zinc Finger E-box-Binding Homeobox 1
PubMed: 31674718
DOI: 10.1002/cam4.2667 -
Journal of Bronchology & Interventional... Oct 2017
Topics: Ameloblastoma; Bronchi; Bronchial Neoplasms; Humans; Lung; Lung Neoplasms; Male; Middle Aged; Neoplasm Recurrence, Local; Tomography, X-Ray Computed
PubMed: 28169911
DOI: 10.1097/LBR.0000000000000365 -
Medicina Oral, Patologia Oral Y Cirugia... Jul 2022Ameloblastomas are benign odontogenic tumors that can eventually mimic the clinical and radiological features of apical periodontitis. The aim of the present study was...
BACKGROUND
Ameloblastomas are benign odontogenic tumors that can eventually mimic the clinical and radiological features of apical periodontitis. The aim of the present study was to evaluate the clinical, radiological and histological characteristics from a series of ameloblastomas mimicking apical periodontitis diagnosed in a 14-year period.
MATERIAL AND METHODS
all cases histologically diagnosed as ameloblastomas from 2005 to 2018 presenting a clinical diagnosis of periapical lesion of endodontic origin were selected for the study. Clinical, radiological and histological characteristics from all cases were tabulated and descriptively and comparatively analyzed.
RESULTS
Twenty cases composed the final sample, including 18 solid and 2 unicystic ameloblastomas. Mean age of the affected patients was in the fifth decade with predilection for males (72%). The most common anatomical location was the posterior mandible (55%) and most cases presented a radiolucent unilocular (80%) well-defined (95%) image. Most cases were asymptomatic, but the presence of local swelling and bone cortical rupture were common.
CONCLUSIONS
Ameloblastomas mimicking periapical lesions of endodontic origin are mostly diagnosed in adult males as well-defined radiolucent unilocular lesions producing local swelling and bone cortical rupture.
Topics: Adult; Ameloblastoma; Humans; Male; Odontogenic Tumors; Periapical Periodontitis; Radiography
PubMed: 35660730
DOI: 10.4317/medoral.25338 -
Medicina Oral, Patologia Oral Y Cirugia... Sep 2022Ep-CAM, a transmembrane glycoprotein expressed in most epithelium in normal conditions, has diverse roles in these tissues, including in cell adhesion, proliferation,...
BACKGROUND
Ep-CAM, a transmembrane glycoprotein expressed in most epithelium in normal conditions, has diverse roles in these tissues, including in cell adhesion, proliferation, differentiation, cell cycle regulation, migration and intracellular signaling. It is also over-expressed in most malignant neoplasia, participating in the initiation, progression, and metastatic dissemination of the tumor. The expression and roles of this protein in oral neoplasia, particularly in odontogenic tumors, remain unestablished. The objective of this study consisted in analyzing the expression of this protein in ameloblastoma and tooth germ.
MATERIAL AND METHODS
Ep-CAM (MOC-31) expression was evaluated by immunohistochemistry in tooth germs (TG) (n = 16) ameloblastomas (AM) (n = 60) and 2 ameloblastic carcinomas. Sections were visualized in their totality with an optical microscope, and positivity observed in cell membrane and cytoplasm was graded according to the following semi-quantitative scale: Neg, "essentially unstained", for negative sections or staining <5% of cells; + for staining of 5-50% of cells; ++ for staining >50% of cells.
RESULTS
Most tooth germs expressed MOC-31 (81.3%), strong staining was observed both in the inner epithelium of the enamel organ and in the adjacent stellate reticulum. 16.7% of the AM cases showed MOC-31 expression, the immunoexpression expression was diffuse at the cytoplasmic and membrane level. The only two cases of ameloblastic carcinoma included were strong positive to MOC-31. No correlation was observed between protein expression and gender, age, clinical variants, or histological subtypes.
CONCLUSIONS
Overexpression was found in TG and ameloblastic carcinoma compared to AM; further studies with different experimental strategies are suggested to clarify the biological significance of this finding.
Topics: Ameloblastoma; Carcinoma; Epithelial Cell Adhesion Molecule; Humans; Odontogenic Tumors; Tooth Germ
PubMed: 35975801
DOI: 10.4317/medoral.25145 -
Head and Neck Pathology Jun 2020The goal of this study was to investigate the immunolocalization of inositol 1,4,5-trisphosphate receptor (IP3R) and vacuolar ATPase (V-ATPase) in ameloblastomas with...
The goal of this study was to investigate the immunolocalization of inositol 1,4,5-trisphosphate receptor (IP3R) and vacuolar ATPase (V-ATPase) in ameloblastomas with special attention to the invasive front. Thirty-seven cases of previously diagnosed formalin-fixed paraffin-embedded (FFPE) human ameloblastoma samples were selected for this study. The samples were grouped according to the predominant histologic pattern and comprised twelve plexiform, eighteen follicular, and seven unicystic ameloblastomas. Of the unicystic variants, six demonstrated purely luminal and intraluminal growth, and one displayed mural extension. One granular cell variant was included in the follicular ameloblastoma group. All specimens were evaluated for IP3R and V-ATPase expression by immunohistochemistry (IHC). IP3R was positive in columnar cells, similar to ameloblasts, and non-peripheral cells in all samples. In the area of tumor protrusion and front of invasion, membranous and cystoplasmic IP3R expression was observed. In contrast, areas adjacent to tumoral protrusion demonstrated only membranous staining patterns. V-ATPase was not expressed in peripheral columnar cells of the unicystic and granular cell variants of ameloblastoma; however, strong staining was present in these cells in plexiform ameloblastomas, follicular ameloblastomas, and areas of mural growth of unicystic ameloblastomas. In areas of tumor protrusion, reactivity for V-ATPase was observed with both membranous and cytoplasmic staining, while other areas showed only membranous V-ATPase. These findings suggest that concomitant immunolocalization of IP3R and V-ATPase, with both cytoplasmic and membranous expression in the peripheral columnar cells, may indicate the invasive potential of ameloblastomas. Furthermore, these results suggest the tumoral spread of ameloblastomas may be correlated with the autophagy process and channelopathy. The expression of these proteins could establish a baseline for future research and provide therapeutic targets for treatment of ameloblastomas.
Topics: Ameloblastoma; Biomarkers, Tumor; Humans; Immunohistochemistry; Inositol 1,4,5-Trisphosphate Receptors; Jaw Neoplasms; Vacuolar Proton-Translocating ATPases
PubMed: 31183746
DOI: 10.1007/s12105-019-01044-y -
Archivos de Bronconeumologia Jul 2023
Topics: Humans; Ameloblastoma; Lung Neoplasms; Neoplasm Recurrence, Local
PubMed: 37270406
DOI: 10.1016/j.arbres.2023.04.005 -
Journal of Oral Pathology & Medicine :... Nov 2021Adenoid ameloblastoma is a rare epithelial neoplasm, histologically characterized by the presence of ameloblastoma-like features, duct-like structures, epithelial...
BACKGROUND
Adenoid ameloblastoma is a rare epithelial neoplasm, histologically characterized by the presence of ameloblastoma-like features, duct-like structures, epithelial whorls, and cribriform architecture. Dentinoid material is usually present. Some advocate adenoid ameloblastoma is an ameloblastoma variant. However, there are overlapping features not only with ameloblastoma, but also with adenomatoid odontogenic tumor. Most ameloblastomas are characterized by the presence of BRAF p.V600E mutations and adenomatoid odontogenic tumors harbor signature KRAS mutations. The molecular features of adenoid ameloblastoma remain unknown.
METHODS
Nine adenoid ameloblastoma cases were screened by TaqMan allele-specific qPCR to assess BRAF p.V600E, ameloblastoma signature mutation, and KRAS p.G12V and p.G12R, adenomatoid odontogenic tumor signature mutations.
RESULTS
BRAF and KRAS mutations were not detected in any of the adenoid ameloblastoma cases.
CONCLUSION
The molecular results support adenoid ameloblastoma as an entity distinct from adenomatoid odontogenic tumor and ameloblastoma.
Topics: Adenoids; Ameloblastoma; Humans; Mutation; Neoplasms, Glandular and Epithelial; Odontogenic Tumors; Proto-Oncogene Proteins B-raf; Proto-Oncogene Proteins p21(ras)
PubMed: 34549835
DOI: 10.1111/jop.13243 -
The Journal of Craniofacial SurgeryTo investigate the clinical characteristics of oral and maxillofacial tumors in children and adolescents.
PURPOSE
To investigate the clinical characteristics of oral and maxillofacial tumors in children and adolescents.
METHODS
This is a retrospective study of patients who had oral and maxillofacial tumors under the age of 18 years and were treated at the Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology from January 1990 to July 2021 (31 y). Their general conditions, pathological diagnosis, gender, age, and anatomical location were counted to analyze their morbidity and composition characteristics.
RESULTS
This study contained 5405 cases, including 2903 male patients and 2502 female patients, with a median age of 9 years. Peak incidence was observed in the 14 to 18 years age group. The mandible (22.15%), maxilla (11.75%), and tongue (9.25%) were the most common sites of incidence. Malignant and intermediate type tumors accounted for 13.04%, benign tumors and tumor-like lesions for 55.67%, most often occurs in the maxillofacial bone, of which fibro-osseous lesions constitute an important part. Cysts accounted for 31.29%. Among the tumors occurring in the jaws, the most common malignant type was sarcoma, and ameloblastoma was the most common benign tumor. Malignant jaw tumors were mostly treated by resection, 10.64% by fibular flap reconstruction. While benign jaw tumors and tumor-like lesions were mostly treated by resection or curettage.
CONCLUSIONS
The distribution of anatomical location and pathological types of oral and maxillofacial tumors in children has certain characteristics, so that the selection of their treatment options is different from that of adults due to the consideration of the growth and developmental characteristics of children.
Topics: Adult; Humans; Child; Male; Female; Adolescent; Retrospective Studies; Jaw Neoplasms; Ameloblastoma; Surgery, Oral; Soft Tissue Neoplasms
PubMed: 37271868
DOI: 10.1097/SCS.0000000000009371 -
International Journal of Oral and... Mar 2016Opinions regarding the treatment of multicystic ameloblastoma are divergent due to its benign nature and the high rate of recurrence if not adequately excised. The aim... (Review)
Review
Opinions regarding the treatment of multicystic ameloblastoma are divergent due to its benign nature and the high rate of recurrence if not adequately excised. The aim of the present study was to perform a systematic review of the literature for a qualitative and quantitative assessment of studies addressing primary multicystic ameloblastoma with regard to treatment and recurrence. Searches were conducted of the Ovid Medline and Embase databases for articles published up to January 2014. Based on predefined eligibility criteria, studies were selected in a two-stage screening process conducted by two independent reviewers. Quality assessment of the selected articles was performed using the modified criteria of the Agency for Healthcare Research and Quality. The meta-analysis was performed using Review Manager (RevMan) software. Statistical heterogeneity was investigated by performing a χ(2) test at the 5% significance level (P<0.05) and determining I(2). The relative risk of recurrence was 3.15-fold greater (95% confidence interval 1.98-5.00) when conservative treatment was performed on primary multicystic ameloblastoma in comparison to radical treatment (P<0.00001 for treatment effect; I(2)=0% and P=0.48 for heterogeneity). The findings justify the treatment of primary multicystic ameloblastoma with bone resection.
Topics: Ameloblastoma; Humans; Jaw Neoplasms; Neoplasm Recurrence, Local; Risk Factors; United States
PubMed: 26792147
DOI: 10.1016/j.ijom.2015.12.016 -
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