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Journal of Clinical and Experimental... Mar 2021Ameloblastoma is a locally aggressive tumor, originated from odontogenic epithelium, and affects the jawbones with an elevated recurrence rate. The molecular mechanisms... (Review)
Review
BACKGROUND
Ameloblastoma is a locally aggressive tumor, originated from odontogenic epithelium, and affects the jawbones with an elevated recurrence rate. The molecular mechanisms involved with the pathogenesis of this tumor remain undetermined. This review aimed to describe the current data regarding epigenetic alterations in ameloblastoma.
MATERIAL AND METHODS
A systematized electronic search was performed in the English-language literature in three databases, combining the following keywords: ameloblastoma, epigenetic, methylation, noncoding RNA, histone acetylation.
RESULTS
According to the gathered results of 11 studies in this review, epigenetic alterations could induce the development and progression of ameloblastoma. DNA methylation has been the most assessed mechanism in ameloblastomas.
CONCLUSIONS
Current literature data indicate that epigenetic events can be involved in the etiopathogenesis of ameloblastomas. Ameloblastoma, epigenetic, methylation, noncoding RNA, histone acetylation.
PubMed: 33680332
DOI: 10.4317/jced.56191 -
Sultan Qaboos University Medical Journal Aug 2023Papilliferous keratoameloblastoma (PKA) is a rare entity, and not much is known about its clinicodemographic features or biological nature. This review aimed to provide... (Review)
Review
Papilliferous keratoameloblastoma (PKA) is a rare entity, and not much is known about its clinicodemographic features or biological nature. This review aimed to provide clarity regarding the characterisation of the demographic, clinical, radiological and histopathological features of PKA. Case reports of PKA were identified through a systematic search across multiple databases. The search yielded a total of 10 cases, half of which were of Indian origin. All the cases invariably occurred in the mandibular posterior region and involved the right side; only one case primarily involved the left side of the mandible. PKA should be considered a variant of the conventional ameloblastoma that is towards the more aggressive end of the spectrum. It tends to occur in older individuals (in their fifth decade or older), with a marked propensity to occur in the right mandibular posterior region. Surgical resection with diligent follow-up is warranted in the treatment of PKA.
Topics: Humans; Aged; Ameloblastoma; Mandible; Thorax
PubMed: 37655071
DOI: 10.18295/squmj.5.2023.021 -
The Japanese Dental Science Review Nov 2021Ameloblastoma is benign odontogenic tumours that mainly occur in the jawbone. This tumour induces aggressive invasion into the surrounding bone and has a high recurrence... (Review)
Review
Ameloblastoma is benign odontogenic tumours that mainly occur in the jawbone. This tumour induces aggressive invasion into the surrounding bone and has a high recurrence rate after surgery. Therefore, mandibular resection is performed in many patients with this tumour, causing aesthetic and functional problems. It is necessary to develop a novel treatment strategy for ameloblastoma, but there are currently no innovative treatments. Although our understanding of the molecular biological mechanisms of ameloblastoma is still insufficient, there have been many recent reports of new molecular biological findings on ameloblastoma. Therefore, bioactive factors that have potential for novel therapeutic methods, such as molecular targeted therapy, have been discovered in ameloblastoma. In this review, we summarize the molecular biological findings of ameloblastoma reported over several decades, focusing on factors involved in invasion into surrounding tissues and disease-specific gene mutations. We also mention the effect of the interaction between tumour cells and stromal components in ameloblastoma on tumour development. Oral surgery, Odontogenic tumor, Ameloblastoma.
PubMed: 33737992
DOI: 10.1016/j.jdsr.2020.12.003 -
Journal of Oncology 2022Ameloblastoma is a slow-growing epithelial odontogenic neoplasm of the jaws with a high recurrence rate. The main treatment strategies for this lesion are radical or...
OBJECTIVES
Ameloblastoma is a slow-growing epithelial odontogenic neoplasm of the jaws with a high recurrence rate. The main treatment strategies for this lesion are radical or conservative surgical approaches. The aim of the present study was to analyze clinical presentations, histological types, and treatment strategies of recurrent ameloblastoma and to define its disease-free survival (DFS) rate.
MATERIALS AND METHODS
Twenty-four cases of recurrent ameloblastomas, treated between January 2009 and July 2021, were enrolled in this study. Medical files from each patient, including gender, age, size of the lesion, localization, patient complaints, clinical manifestation, radiographic appearance, histological type, surgical management, and treatment results were reviewed and analyzed retrospectively.
RESULT
Out of 69 operated primary ameloblastomas, the rate of recurrence was 35%. Out of 24 recurrent cases, 21 developed after conservative treatment and 3 after radical treatment. In most cases, recurrences were found in the mandible ( = 20). A unilocular pattern was predominant in radiographic examination (44%). Estimated 3-year DFS was 84.5 ± 4.8%, and the 5-year and 10-year DFS were 73.0 ± 6.3% and 43.9 ± 8.343.9 ± 8.3%, respectively.
CONCLUSION
Results obtained in the present retrospective study proved the necessity of long-term follow-up after both conservative and radical treatment approaches. The DFS median in our study was 8 years (95% CI 6 years-10 years). For recurrent cases, radical resection with histologically free margins after exact MRI determination of the ameloblastoma border within the soft tissues should be considered as the method of choice to avoid secondary recurrence.
PubMed: 35983087
DOI: 10.1155/2022/2148086 -
Archives of Oral Biology Aug 2022This article aims to systematically and comprehensively discuss molecular biology-related progress and targeted therapeutic strategies for ameloblastoma, which are... (Review)
Review
OBJECTIVE
This article aims to systematically and comprehensively discuss molecular biology-related progress and targeted therapeutic strategies for ameloblastoma, which are expected to be helpful for the diagnosis and treatment of ameloblastoma.
DESIGN
A comprehensive review of scientific literature relevant to ameloblastoma, including the latest classification, global epidemiology, molecular biology advances, and targeted therapy.
RESULTS
Among the 156 articles cited, a total of 20 non-coding RNAs, 13 genes, 27 proteins, and 8 pathways were involved, which play a variety of roles in ameloblastoma. These roles include participation in the biological behaviours of ameloblastoma migration, differentiation, and apoptosis; detection of ameloblastoma proliferative properties; detection of ameloblastoma angiogenesis; and identification of ameloblastoma carcinogenesis.
CONCLUSIONS
At present, some progress has been made in molecular biology and targeted therapy for ameloblastoma involving BRAF and SMO genes. The related non-coding RNAs, genes, proteins, and pathways involved in this review provide new ideas and directions for the occurrence and development of ameloblastoma and have the potential to become new gene therapy targets.
Topics: Ameloblastoma; Humans; Molecular Biology; Mutation; Proto-Oncogene Proteins B-raf
PubMed: 35597128
DOI: 10.1016/j.archoralbio.2022.105454 -
Frontiers in Oral Health 2021DNA methyltransferases (DNMTs) and the histone modification H3K9ac are epigenetic markers. This study aimed to describe the immunohistochemical expression of DNMT1,...
DNA methyltransferases (DNMTs) and the histone modification H3K9ac are epigenetic markers. This study aimed to describe the immunohistochemical expression of DNMT1, DNMT3A, DNMT3B, and H3K9ac in the dental follicle (DF), ameloblastoma (AME), and ameloblastic carcinoma (AC), correlating these expressions with the recurrence and aggressive behavior in ameloblastoma. Immunohistochemical reactions were performed in 10 human DFs, 38 ameloblastomas, and 6 AC samples. Another 59 ameloblastomas assembled in a tissue microarray were used to compare the immunoexpression with the clinical, radiographic, and histopathological characteristics and the presence of BRAFv600e mutation. Each slide was digitized as a high-resolution image and quantified by Aperio ScanScope Nuclear V9 software. All statistical analyzes were performed using GraphPad Prism statistical software. DNMT3B expression was higher in ameloblastomas than in the DFs, while the AC overexpressed all proteins. The ameloblastomas with BRAFv600e mutation, vestibular/lingual, or vestibular/palatine bone cortical disruption and maxilla involvement showed DNMT1 overexpression, while recurrent cases had high DNMT3B levels. DNA methylation and histone modification might play a role in the development, clinical aggressiveness, and recurrence rates of ameloblastoma, such as the progression to AC. Further investigation about gene methylations in ameloblastomas is needed to better understand its relationship with aggressiveness and recurrence.
PubMed: 35048062
DOI: 10.3389/froh.2021.751162 -
Indian Journal of Dental Research :... 2022Ameloblastoma is a benign, locally aggressive neoplasm that needs extensive surgical resection. The goal of this article is to obtain an in-depth review of benign... (Review)
Review
Ameloblastoma is a benign, locally aggressive neoplasm that needs extensive surgical resection. The goal of this article is to obtain an in-depth review of benign ameloblastomas to determine the available level of evidence and the possible benefit of targeted therapeutics for the treatment of ameloblastoma and BRAF V600E mutation in ameloblastoma. An electronic literature search was conducted according to PRISMA guidelines in PubMed/MEDLINE, EBSCO, and Web of Science for eligible studies published between 1975 and 2021. The systematic review is registered with INPLASY (INPLASY202260018). The review included 2 case series and 17 case reports. The histopathological type, anatomic location, expression of BRAF mutation, additional mutations, and molecular-targeted therapies of the 19 reviewed articles were summarized and tabulated. Interestingly, the majority of the primary site of ameloblastoma was located in the mandible (80.9%) compared to the maxilla (17%). The tumour size was reported in nine of the included studies. Most of the included studies in the review exhibited ameloblastoma with BRAF V600E mutations and responded to molecular-targeted therapies. Molecular therapies employing BRAF and/or MEK inhibitors in ameloblastoma with BRAF V600E mutations proved to be an appropriate treatment based on the limited available evidence. It is essential further to deepen our understanding at the clinical and molecular level to enhance the precision of management of ameloblastoma.
Topics: Humans; Ameloblastoma; Molecular Targeted Therapy; Mutation; Proto-Oncogene Proteins B-raf
PubMed: 36656197
DOI: 10.4103/ijdr.ijdr_456_22 -
International Journal of Dentistry 2022CDC7 is a serine-threonine kinase that plays a key role in initiating DNA replication. It has been implicated in the growth and invasion of many pathologic lesions and...
OBJECTIVES
CDC7 is a serine-threonine kinase that plays a key role in initiating DNA replication. It has been implicated in the growth and invasion of many pathologic lesions and suggested as a diagnostic marker. The aim of this study was to evaluate CDC7 in some odontogenic tumors.
MATERIALS AND METHODS
In this cross-sectional study, 45 cases, including 19 ameloblastomas, 15 dentigerous cysts, 7 ameloblastic fibromas, and 4 adenomatoid odontogenic tumors (AOT), were studied immunohistochemically. ANOVA and post hoc methods were used for statistical analysis.
RESULTS
CDC7 expression was observed in 93% of tumors and all dentigerous cysts. The expression rate was low. The results showed a higher expression rate of CDC7 in ameloblastoma and ameloblastic fibroma compared to AOT (=0.009 and =0.048, respectively). Ameloblastoma and ameloblastic fibroma were not significantly different in CDC7 expression (=0.6).
CONCLUSION
According to the results, the expression of the CDC7 protein in odontogenic tumors is low. The higher expression of CDC7 in ameloblastoma and ameloblastic fibroma in comparison with AOT confirms the hamartomatous growth of the latter, so it can be considered as a potential diagnostic marker. Future studies with a larger sample size are suggested to obtain a cut-off point for diagnostic purposes.
PubMed: 36483932
DOI: 10.1155/2022/6336003 -
Modern Pathology : An Official Journal... Nov 2022Adenoid ameloblastoma is a very rare benign epithelial odontogenic tumor characterized microscopically by epithelium resembling conventional ameloblastoma, with...
Adenoid ameloblastoma is a very rare benign epithelial odontogenic tumor characterized microscopically by epithelium resembling conventional ameloblastoma, with additional duct-like structures, epithelial whorls, and cribriform architecture. Dentinoid deposits, clusters of clear cells, and ghost-cell keratinization may also be present. These tumors do not harbor BRAF or KRAS mutations and their molecular basis appears distinct from conventional ameloblastoma but remains unknown. We assessed CTNNB1 (beta-catenin) exon 3 mutations in a cohort of 11 samples of adenoid ameloblastomas from 9 patients. Two of the 9 patients were female and 7 male and in 7/9 patients the tumors occurred in the maxilla. Tumors of 4 of these 9 patients harbored CTNNB1 mutations, specifically p.Ser33Cys, p.Gly34Arg, and p.Ser37Phe. Notably, for one patient 3 samples were analyzed including the primary tumour and two consecutive recurrences, and results were positive for the mutation in all three tumors. Therefore, 6/11 samples tested positive for the mutation. In the 6 mutation-positive samples, ghost cells were present in only 2/6, indicating beta-catenin mutations are not always revealed by ghost cell formation. Dentinoid matrix deposition was observed in 5/6 mutation-positive samples and clear cells in all 6 cases. None of the cases harbored either BRAF or KRAS mutations. Beta-catenin immunoexpression was assessed in the samples of 8 patients. Except for one wild-type case, all cases showed focal nuclear expression irrespective of the mutational status. Together with the absence of BRAF mutation, the detection of beta-catenin mutation in adenoid ameloblastomas supports its classification as a separate entity, and not as a subtype of ameloblastoma. The presence of this mutation may help in the diagnosis of challenging cases.
Topics: Humans; Male; Female; Ameloblastoma; beta Catenin; Proto-Oncogene Proteins B-raf; Adenoids; Proto-Oncogene Proteins p21(ras); Odontogenic Tumors; Mutation
PubMed: 35840721
DOI: 10.1038/s41379-022-01125-4 -
Cancers Nov 2022The discovery that ameloblastoma has a high mutation incidence of V600E may enable a better investigation of pathophysiology. However, there is inconsistent evidence... (Review)
Review
The discovery that ameloblastoma has a high mutation incidence of V600E may enable a better investigation of pathophysiology. However, there is inconsistent evidence regarding this mutation occurrence and its association with clinical information. This systematic review and meta-analysis aim to pool the overall mutation prevalence of V600E in reported ameloblastoma cases and to determine its association with patient demographic and clinicopathological features. Following the PRISMA guidelines, a comprehensive article search was conducted through four databases (Scopus, Google Scholar, PubMed, and Web of Science). Seventeen articles between 2014 and 2022 met the inclusion criteria with 833 ameloblastoma cases. For each included study, the significance of V600E on the outcome parameters was determined using odd ratios and 95% confidence intervals. Meta-analysis prevalence of V600E in ameloblastoma was 70.49%, and a significant meta-analysis association was reported for those younger than 54 years old and in the mandible. On the contrary, other factors, such as sex, histological variants, and recurrence, were insignificant. As a result of the significant outcome of V600E mutation in ameloblastoma pathogenesis, targeted therapy formulation can be developed with this handful of evidence.
PubMed: 36428683
DOI: 10.3390/cancers14225593