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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 -
BMC Oral Health Aug 2023Ameloblastic carcinoma and metastasising ameloblastoma are rare epithelial odontogenic tumours with aggressive features. Distinguishing between these two lesions is... (Review)
Review
BACKGROUND
Ameloblastic carcinoma and metastasising ameloblastoma are rare epithelial odontogenic tumours with aggressive features. Distinguishing between these two lesions is often clinically difficult but necessary to predict tumour behaviour or to plan future therapy. Here, we provide a brief review of the literature available on these two types of lesions and present a new case report of a young man with an ameloblastoma displaying metastatic features. We also use this case to illustrate the similarities and differences between these two types of tumours and the difficulties of their differential diagnosis.
CASE PRESENTATION
Our histopathological analyses uncovered a metastasising tumour with features of ameloblastic carcinoma, which developed from the ameloblastoma. We profiled the gene expression of Wnt pathway members in ameloblastoma sample of this patient, because multiple molecules of this pathway are involved in the establishing of cell polarity, cell migration or for epithelial-mesenchymal transition during tumour metastasis to evaluate features of tumor behaviour. Indeed, we found upregulation of several cell migration-related genes in our patient. Moreover, we uncovered somatic mutation BRAF p.V600E with known pathological role in cancerogenesis and germline heterozygous FANCA p.S858R mutation, whose interpretation in this context has not been discussed yet.
CONCLUSIONS
In conclusion, we have uncovered a unique case of ameloblastic carcinoma associated with an alteration of Wnt signalling and the presence of BRAF mutation. Development of harmful state of our patient might be also supported by the germline mutation in one FANCA allele, however this has to be confirmed by further analyses.
Topics: Male; Humans; Ameloblastoma; Proto-Oncogene Proteins B-raf; Odontogenic Tumors; Mutation; Carcinoma
PubMed: 37573343
DOI: 10.1186/s12903-023-03259-6 -
Journal of Oral and Maxillofacial... 2024Glucose uptake may be considered the rate-limiting step for the growth and metabolism of the cancer cell. Studies on GLUT1 have shown that GLUT1 is involved in cell...
CONTEXT
Glucose uptake may be considered the rate-limiting step for the growth and metabolism of the cancer cell. Studies on GLUT1 have shown that GLUT1 is involved in cell survival and proliferation in both healthy and pathological circumstances. GLUT1 expression is regarded as one of the crucial elements in the development of local aggressiveness, tumour invasiveness, and metastasis, particularly in malignant tumours. The role of glut1 in odontogenic cysts and tumours has remained uncertain.
AIM
The aim of the study is to assess the expression of Glut1 in dentigerous cysts, odontogenic keratocysts, and ameloblastoma.
SETTINGS AND DESIGN
The study was conducted in GSL Dental College. The study design was a resprospective immunohistochemical study.
METHODS AND MATERIAL
Formalin-fixed, paraffin-embedded blocks of histologically confirmed cases (n = 50), 10 cases of odontogenic keratocysts, dentigerous cysts, ameloblastomas solid, ameloblastomas unicystic, and dental follicles each. Brown colour staining was considered as positive staining for GLUT1. Quantitative analysis was performed by counting the number of labelled cells, and semi-quantitative analysis was conducted by assigning immunostaining intensity scores.
STATISTICAL ANALYSIS
Chi-square test was used to compare differences between the groups. A value of ≤0.05 was considered as statistically significant.
RESULTS
Odontogenic keratocysts and unicystic ameloblastoma showed ≥50% of label cells with strong intensity of staining. Odontogenic keratocysts and solid ameloblastoma showed sub-cellular localisation of staining in the cytoplasm and membrane. Dentigerous cysts exhibited combined nucleus, cytoplasm, and membrane sub-cellular localisation of staining.
CONCLUSIONS
The development of ameloblastomas, odontogenic keratocysts, and dentigerous cysts appears to be influenced by GLUT-1. Variation in its expression may aid in explanation of some of the differences in biological activity of these lesions.
PubMed: 38800443
DOI: 10.4103/jomfp.jomfp_455_23 -
BMJ Case Reports Dec 2021Ameloblastic carcinoma is a rare malignant odontogenic neoplasm that exhibits diverse clinical and radiological presentations. In fact there are several differential...
Ameloblastic carcinoma is a rare malignant odontogenic neoplasm that exhibits diverse clinical and radiological presentations. In fact there are several differential diagnoses during histopathological evaluation too. Lack of adequate reports could not establish the predominant demographic, clinical and radiological presentations. For the same reasons, the role of adjuvant radiotherapy and chemotherapy is also unsubstantiated yet. This case discusses the innocuous clinical and radiological presentation of ameloblastic carcinoma in a 55-year-old man where the diagnostic confirmation was achieved through histopathological evaluation. The differential diagnoses, treatment and follow-up details of this case are discussed in light of the previous published case reports and systematic reviews of case reports in an attempt to increase the sensitisation among dentists towards ameloblastic carcinoma.
Topics: Ameloblastoma; Carcinoma; Diagnosis, Differential; Humans; Male; Mandibular Neoplasms; Middle Aged; Odontogenic Tumors
PubMed: 34906959
DOI: 10.1136/bcr-2021-246907 -
International Journal of Surgery Case... 2017Ameloblastomas are rare head and neck tumors, and yet the most common odontogenic neoplasms. They account for 1% and 11% of all head and neck and odontogenic tumors...
INTRODUCTION
Ameloblastomas are rare head and neck tumors, and yet the most common odontogenic neoplasms. They account for 1% and 11% of all head and neck and odontogenic tumors respectively. Embryologically, they originate from remnants of odontogenic epithelium. Their aggressive, destructive nature, as well as their anticipated high rate of recurrence, even after en bloc resection, poses a surgical predicament.
PRESENTATION
We present a case of a 56 year-old Asian female with a multi-recurrent invasive ameloblastoma. Initially, the lesion was mandibular in location for which she underwent a mandiblectomy. Later on, she presented with a maxillary ameloblastoma with invasion of both the anterior wall of the maxillary sinus and the floor of the orbit. The patient was operated twice and histopathology confirmed a cystic type recurrent ameloblastoma. A year later, she came with recurrent maxillary ameloblastoma and a maxillectomy was done. However, histopathology revealed a follicular ameloblastoma. Three years later, she presented with a retro-orbital ameloblastoma with infiltration to the temporal muscles. The patient was operated and the histopathologic examination revealed a partially cystic lesion with no malignant transformation.
CONCLUSION
This case discusses available treatment options and emphasizes on the importance of long-term patient follow-up due to the biological behavior of ameloblastoma.
PubMed: 27902954
DOI: 10.1016/j.ijscr.2016.11.039 -
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 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 -
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