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Scientific Reports Dec 2021Ameloblastoma is a benign, epithelial cancer of the jawbone, which causes bone resorption and disfigurement to patients affected. The interaction of ameloblastoma with...
Ameloblastoma is a benign, epithelial cancer of the jawbone, which causes bone resorption and disfigurement to patients affected. The interaction of ameloblastoma with its tumour stroma drives invasion and progression. We used stiff collagen matrices to engineer active bone forming stroma, to probe the interaction of ameloblastoma with its native tumour bone microenvironment. This bone-stroma was assessed by nano-CT, transmission electron microscopy (TEM), Raman spectroscopy and gene analysis. Furthermore, we investigated gene correlation between bone forming 3D bone stroma and ameloblastoma introduced 3D bone stroma. Ameloblastoma cells increased expression of MMP-2 and -9 and RANK temporally in 3D compared to 2D. Our 3D biomimetic model formed bone nodules of an average surface area of 0.1 mm and average height of 92.37 [Formula: see text] 7.96 μm over 21 days. We demonstrate a woven bone phenotype with distinct mineral and matrix components and increased expression of bone formation genes in our engineered bone. Introducing ameloblastoma to the bone stroma, completely inhibited bone formation, in a spatially specific manner. Multivariate gene analysis showed that ameloblastoma cells downregulate bone formation genes such as RUNX2. Through the development of a comprehensive bone stroma, we show that an ameloblastoma tumour mass prevents osteoblasts from forming new bone nodules and severely restricted the growth of existing bone nodules. We have identified potential pathways for this inhibition. More critically, we present novel findings on the interaction of stromal osteoblasts with ameloblastoma.
Topics: Ameloblastoma; Animals; Bone Resorption; Core Binding Factor Alpha 1 Subunit; Gene Expression; Humans; Jaw Neoplasms; Matrix Metalloproteinase 2; Neoplasm Invasiveness; Osteoblasts; Osteogenesis; RANK Ligand; Rats; Stromal Cells; Tissue Engineering; Tumor Cells, Cultured; Tumor Microenvironment
PubMed: 34916549
DOI: 10.1038/s41598-021-03484-5 -
Journal of Oral and Maxillofacial... 2023Odontogenic lesions have diverse biological behaviour which is characterised by local invasiveness, and a high recurrence rate. EGFR and survivin was found to be...
CONTEXT
Odontogenic lesions have diverse biological behaviour which is characterised by local invasiveness, and a high recurrence rate. EGFR and survivin was found to be involved in the aggressiveness, recurrences and metastasis of a variety of epithelial malignancies.
AIMS
To assess and compare the expression of EGFR and survivin in Ameloblastoma (AB), Odontogenic keratocyst (OKC) and Calcifying odontogenic cyst (COC).
SETTINGS AND DESIGN
The study's goal was to use immunohistochemistry to assess the qualitative and quantitative expression of EGFR and survivin and to correlate their expression patterns in AB, OKC and COC.
METHODS AND MATERIAL
Study included 30 AB, 15 OKC and 10 COC. All the slides were immunohistochemically analysed for qualitative, quantitative and semi-quantitative data. In each group, the presence of EGFR and survivin was assessed in terms of stain localisation, intensity and percentage of positive cells.
STATISTICAL ANALYSIS USED
Data were analysed using Chi-square test and one-way ANOVA, value < 0.05 was considered statistically significant.
RESULTS
EGFR positivity was found in all cases. Survivin was found to be 96% positive in AB and 100% positive in OKC and COC. Both EGFR and survivin showed predominant cytoplasmic staining. All the slides that are stained with EGFR are also stained with survivin. The intensity varied significantly between the layers. OKC showed higher immunoreactive scores (IRSs).
CONCLUSIONS
The current study provides insight into the role of EGFR and survivin in the pathogenesis of AB, OKC and COC. OKC appears to be more aggressive than ameloblastoma and COC, owing to its higher IRS.
PubMed: 37854905
DOI: 10.4103/jomfp.jomfp_187_22 -
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... 2022Facilitative glucose transporters (GLUTs), which mediate glucose transport across the cell membrane, differ in their tissue distribution and affinity for glucose. GLUT1...
INTRODUCTION
Facilitative glucose transporters (GLUTs), which mediate glucose transport across the cell membrane, differ in their tissue distribution and affinity for glucose. GLUT1 is ubiquitously present and help in the basal uptake of glucose into the cells. Its expression is known to be elevated in conditions that induce hypoxia and by growth factors. GLUT1 is known to be increased in many malignant tumors to meet the metabolic requirements, but its role in odontogenic tumors is not known.
OBJECTIVE
The objective of this study is to evaluate and compare the immunohistochemical expression of GLUT1 in ameloblastoma (AM) and odontogenic keratocyst (OKC).
MATERIALS AND METHODOLOGY
Thirty cases each of AM and OKCs were immunohistochemically stained using anti-GLUT1 antibody according to the standard protocol. Qualitative assessment of GLUT1 expression was done under the categories of distribution, intensity and localization of staining. Quantitative assessment was done using Image J software. The results were tabulated and statistically analyzed.
RESULTS
GLUT1 positivity was observed in 25 (83.3%) cases of OKC and 26 (86.7%) of AM cases. The majority of cells in the suprabasal layer of OKC showed positivity, whereas the equal distribution of staining was observed in the central and peripheral cells of AM.
CONCLUSION
GLUT1 expression in these tumors is suggestive of an increased glucose uptake and probably increased utilization of energy, which may be correlated with their aggressive behavior.
PubMed: 35968192
DOI: 10.4103/jomfp.jomfp_9_21 -
National Journal of Maxillofacial... Aug 2022Ameloblastic fibrosarcoma (AFS) is an extremely rare malignant odontogenic tumor. It is composed of benign odontogenic epithelium, resembling that of ameloblastoma, and...
Ameloblastic fibrosarcoma (AFS) is an extremely rare malignant odontogenic tumor. It is composed of benign odontogenic epithelium, resembling that of ameloblastoma, and a mesenchymal part exhibiting features of fibrosarcoma. The development of this lesion in the jaws is either de novo or from preexisting ameloblastic fibroma which has been well documented. The most commonly affected site within the jaw is the posterior mandible. These tumors show local aggressiveness and a high tendency to recur. We present a case of a 33-year-old female patient with swelling of the right posterior mandible for 2 months and progressive paresthesia of the same region for the past 6 months. Patient's history revealed undergoing surgical enucleation for ameloblastic fibroma before a year in the same region as current swelling. Examination of the swelling revealed an ulceroprolifeartive Growth of 6 × 4.5 cm extending from premolar to molar region. Primary investigation involved biopsy of the swelling, which was reported as sarcoma for which resection of the right hemimandible and selective neck dissection was performed. Following surgery, the final histopathology report of the resected specimen was reported to be AFS. One year after the surgical procedure, the patient is clinically and radiologically disease-free. Considering the aggressive nature of these tumors, it is vital to give an accurate diagnosis through biopsy, which is considered as gold standard diagnostic evidence, so that the surgeon plans the appropriate therapeutic decision. Knowledge of this rare entity and its histologic features as opposed to the more common benign counterparts such as ameloblastoma or ameloblastic fibroma is crucial as the latter involves a conservative treatment approach while the former can only be treated through aggressive resections.
PubMed: 36393933
DOI: 10.4103/njms.NJMS_100_20 -
Journal of Oral Biology and... 2023Metastasizing Ameloblastoma (MA) is an aggressive variant of ameloblastoma (AM) with the ability to metastasize without cytological malignant changes. Thus it aims to... (Review)
Review
BACKGROUND
Metastasizing Ameloblastoma (MA) is an aggressive variant of ameloblastoma (AM) with the ability to metastasize without cytological malignant changes. Thus it aims to comprehensively review the clinico-pathological and prognostic aspects of MA through integration of current literature.
METHODS
Electronic searches were conducted in PubMed-MEDLINE, Scopus, Web of Science and Google Scholar. Two independent reviewers screened abstracts and evaluated paper eligibility. AMSTAR2 checklist was used to assessed methodological quality of included systematic reviews (SRs).
RESULTS
From 390 initial papers, 279 underwent eligibility screening, with five systematic reviews (SRs) meeting inclusion criteria. Six hundred sixty-one MA cases were found in five SRs that were included. MA predominantly affects men, exhibits mandible preference, and occurs in individuals in their fourth or fifth decade. Benign metastatic deposits commonly manifest in lungs and lymph nodes. Distant metastasis probability rises with multiple recurrences and incomplete surgical removal. Tumor recurrence and metastasis unfavorably impact clinical outcomes. Quality of evidence assessment was absent across SRs; four SRs were critically low in methodological quality.
CONCLUSIONS
AM's metastatic potential lacks predictability. Early/multiple recurrences post-treatment may signal poor prognosis, warranting vigilant follow-up. Methodical analysis of each AM case is imperative to comprehend the metastatic-benign histology relationship.
PubMed: 38028232
DOI: 10.1016/j.jobcr.2023.10.006 -
Cureus Oct 2023Ameloblastoma is one of the most prevalent but enigmatic benign odontogenic tumors of the jaw, accounting for approximately 10% of all maxillary and mandibular tumors.... (Review)
Review
Ameloblastoma is one of the most prevalent but enigmatic benign odontogenic tumors of the jaw, accounting for approximately 10% of all maxillary and mandibular tumors. This neoplasia is distinguished by exhibiting several clinical and histological variants along with several mutations that affect its behavior. The ameloblastoma treatment plan is determined by the tumor's size, anatomical location, histologic variant, and anatomical involvement. On chromosome 7, there is a proto-oncogene called BRAF. When BRAF is mutated, it becomes an oncogene and continuously produces proteins like MEK and ERK, members of mitogen-activated protein kinase (MAPK). In the signaling pathway, these proteins activate transcription factor inside the nucleus that helps in cell division and growth. Numerous neoplasms have been linked to more than 40 BRAF mutations. The most common one is BRAF proto-oncogene serine/threonine kinase (BRAF) V600E, whose treatment has been linked to a positive outcome. BRAF inhibitors like vemurafenib, dabrafenib, and sorafenib have shown excellent results, especially in metastatic ameloblastoma. BRAF, particularly in the case of metastatic ameloblastoma, inhibitors such as vemurafenib, dabrafenib, and sorafenib, has demonstrated outstanding results. Targeted therapies have been employed as adjuvant therapies to enhance cosmetic outcomes, even though no reports of serial cases demonstrate their effectiveness in ameloblastomas. In the treatment of ameloblastomas, the identification of BRAF V600E and additional mutations as the prime targeted therapies has proven to be a significant breakthrough where surgical treatment was contraindicated. In this article, we review the presence of BRAF V600E mutations, their inhibitors, and targeted therapies in ameloblastoma.
PubMed: 38021761
DOI: 10.7759/cureus.47682 -
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 -
Head and Neck Pathology Dec 2021Dentigerous cysts, also known as follicular cysts, are among the most common developmental cysts of the gnathic bones. The majority of cases are clinically asymptomatic...
Dentigerous cysts, also known as follicular cysts, are among the most common developmental cysts of the gnathic bones. The majority of cases are clinically asymptomatic and discovered incidentally on panographic radiographs during routine dental care. The cyst appears as a radiolucency, classically unilocular, associated with the crown of an unerupted or impacted tooth. Usually diagnosed in the 2nd-3rd decade, third molars of the mandible are the most commonly affected teeth. Histologically, dentigerous cysts demonstrate a fibrous or fibromyxoid connective tissue wall lined by squamous epithelium, classically lacking rete ridges. Inflammation may introduce histologic changes, however. The differential diagnosis includes hyperplastic dental follicle, periapical or radicular cyst, unicystic ameloblastoma, odontogenic keratocyst, and other odontogenic cysts and tumors. While the findings are generally classic and pose no diagnostic dilemma, the diagnosis is best made in the context of the appropriate clinical and radiographic setting. Submitted tissue with a lack of history, to include a detailed relationship with the affected tooth, may result in misdiagnosis and subsequent confusion for the clinician. So, despite its simple features, dentigerous cysts are not uncommonly mischaracterized. Therefore a review of a classic case of dentigerous cyst is presented.
Topics: Dentigerous Cyst; Humans; Male; Mandibular Diseases; Radiography, Panoramic; Young Adult
PubMed: 33881736
DOI: 10.1007/s12105-021-01327-3 -
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