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Histology and Histopathology Feb 2024Hypoxia is characterized by a disparity between supply and demand of oxygen. The association between hypoxia and head and neck tumors is a topic of significant interest.... (Review)
Review
Hypoxia is characterized by a disparity between supply and demand of oxygen. The association between hypoxia and head and neck tumors is a topic of significant interest. Tumors frequently encounter areas with inadequate oxygen supply, resulting in a hypoxic microenvironment. Ameloblastoma is one of the most common benign odontogenic tumors of the maxillofacial region. It is a slow-growing but locally invasive tumor with a high recurrence rate. The literature has demonstrated the correlation between hypoxia and ameloblastoma, revealing a discernible link between the heightened expression of hypoxic markers in low oxygen conditions. This association is intricately tied to the tumoral potential for invasion, progression, and malignant transformation. Hypoxia profoundly influences the molecular and cellular landscape within ameloblastic lesions. The present review sheds light on the mechanisms, implications, and emerging perspectives in understanding this intriguing association to clarify the dynamic relationship between hypoxia and ameloblastoma.
PubMed: 38362601
DOI: 10.14670/HH-18-718 -
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 -
Journal of Oral and Maxillofacial... 2023Odontogenic, non-inflammatory maxillofacial cysts and tumours vary greatly in their ability to grow and cause local tissue destruction. Despite their common embryologic...
INTRODUCTION
Odontogenic, non-inflammatory maxillofacial cysts and tumours vary greatly in their ability to grow and cause local tissue destruction. Despite their common embryologic origin, the biologic mechanisms responsible for this diverse array of clinical behaviour are largely unknown. Unfortunately, even with accurate tissue diagnosis and appropriate surgical management, these tumours have relatively high recurrence rates. While this may be related to surgical technique, it may also be due to intrinsic tumour biology. SOX2 is differentially expressed in odontogenic cysts and tumours, which has an impact over patient prognosis. This could be related to their diverse cells of origin or stages of histogenesis. SOX2 is expressed in OKC and ameloblastoma, and in this study, we look forward to find altered levels and intensity of SOX2 in the above-mentioned lesions.
AIM AND OBJECTIVES
To profile the expression of SOX2 in odontogenic keratocyst (OKC) and ameloblastomaTo compare the intensity of these lesions, analyse their intrinsic feature and predict their recurrence.
MATERIAL AND METHODS
Histopathologically diagnosed cases of OKC and ameloblastoma will be selected ( = 40). Paraffin-embedded, formalin-fixed sections of these lesions will be stained for SOX2 marker using a standard immunohistochemical technique. Positive control will be taken as oral squamous cell carcinoma and negative control will be taken as normal oral mucosa.
RESULTS
A comparison between the stained cell types in odontogenic keratocyst and ameloblastoma revealed statistically significant differences. The immunoreactivity scores of SOX2 were analysed in both groups. The results indicated that 45% of OKC cases exhibited strongly positive reactivity, while 65% of ameloblastoma cases were negative. Statistical analysis demonstrated highly significant differences in the frequency of SOX2 expression between the two groups, with a higher frequency of negative expression in ameloblastoma.
CONCLUSION
Stem cell markers have been observed in these lesions, suggesting the acquisition of stem-like properties by tumour cells, which can affect patient prognosis. Specifically, the marker SOX2 shows differential expression in odontogenic cysts and tumours. High expression of SOX2 in OKC indicates the presence of stem cells with significant self-renewal and proliferative properties, potentially signifying neoplastic behaviour. In contrast, weak or absent expression of SOX2 in ameloblastoma suggests different molecular pathways involved in its neoplastic behaviour.
PubMed: 38304494
DOI: 10.4103/jomfp.jomfp_265_23 -
Cureus Jul 2023Ameloblastoma is one of the most prevalent odontogenic tumors of epithelial origin, with several histological variations. However, among these variants, 'hybrid...
Ameloblastoma is one of the most prevalent odontogenic tumors of epithelial origin, with several histological variations. However, among these variants, 'hybrid ameloblastoma' is infrequent and anomalous. The current case study demonstrates the existence of hybrid ameloblastoma in a 27-year-old female patient, which included desmoplastic, follicular, and acanthomatous patterns. The right side of the mandible was affected by tumor growth, with extensive bone involvement and neural invasion, resulting in a loss of sensation on that side. Although the tumor grows at a gradual pace, its enigmatic manifestation highlights the significance of a meticulous diagnosis. The course of treatment involved comprehensive resection of the tumor segment, followed by the recommended reconstructive surgery during the postoperative follow-up period.
PubMed: 37637513
DOI: 10.7759/cureus.42512 -
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 -
Indian Journal of Otolaryngology and... Sep 2023Introduction: Odontogenic tumors encompass a heterogeneous group of lesions that range from hamartomatous lesions to malignancy. Considerable variation in histologic...
UNLABELLED
Introduction: Odontogenic tumors encompass a heterogeneous group of lesions that range from hamartomatous lesions to malignancy. Considerable variation in histologic presentation can mislead their accurate diagnosis and categorization. Ameloblastoma is generally well understood and is easy to diagnose but there has been a constant change in the classification systems ever since Broca classified odontogenic tumors in the year 1867. Over the years, it has been modified by the World Health Organization with many additions and omissions. This dynamic change is based on the result and conclusions of molecular and genetic studies with the last modification in 2017. Case Report: We present two cases of females aged 32 and 60 years who reported with facial swellings, revealed the presence of distinct histopathological findings and were diagnosed as ameloblastoma with dentinoid or adenoid ameloblastoma. Literature search revealed dearth of distinct forms of ameloblastoma that show the formation of duct like structures and dentinoid. Conclusion: It is interesting to highlight such cases as the biological behavior is still unexplored due to paucity of relevant studies and follow up of patients. Understanding the pathogenesis and the histopathological characteristics of the newer entities will enable the prompt diagnosis, treatment plan and expanding the spectrum of the lesions.
SUPPLEMENTARY INFORMATION
The online version contains supplementary material available at 10.1007/s12070-023-03534-6.
PubMed: 37636784
DOI: 10.1007/s12070-023-03534-6 -
Journal of Stomatology, Oral and... Dec 2023Clinico-histopathologic assessment of patients with ameloblastoma and ameloblastic carcinoma remains the best diagnostic modality for the tumors. However, in cases where...
BACKGROUND
Clinico-histopathologic assessment of patients with ameloblastoma and ameloblastic carcinoma remains the best diagnostic modality for the tumors. However, in cases where the criteria for arriving at a definitive diagnosis are not clearcut, the pathologist is faced with a dilemma and thus an imperative need for adjunct diagnostic methods.
OBJECTIVES
To evaluate/compare the immunohistochemical expression of NM23 in classical, borderline (atypical) ameloblastoma and ameloblastic carcinoma and to assess usefulness of NM23 in closing diagnostic gaps between ameloblastoma and ameloblastic carcinoma.
METHODS
Twenty-four (24) cases of ameloblastoma, 10 ameloblastoma with classical histopathologic features, 8 with nonclassical histopathology [atypical], and 6 cases of ameloblastic carcinoma were selected from cases seen at the Oral Pathology Laboratory of the Lagos State University College of Medicine, Nigeria. NM23 immunostaining protocol was done on the selected tissue blocks and evaluated using Sinicrope method. Analysis was done using R language.
RESULTS
Positive NM23 staining was observed in all cases of ameloblastoma and ameloblastic carcinoma, with more intense staining observed in the stellate reticulum-like areas than in the ameloblast-like areas. Ameloblastic carcinoma stained intensely with NM23 (100%) compared with atypical cases (37.5%) and ameloblastoma (20.0%; p = 0.04). The mean aggregate score was also significantly higher in AC (11 ± 2.4; p = 0.01). The mean aggregate score was also significant amongst growth pattern of ameloblastoma (p = 0 0.02).
CONCLUSIONS
The findings in this study reveal the usefulness of NM23 in differentiating ameloblastoma from ameloblastic carcinoma; a more comprehensive study with a larger sample size is recommended to corroborate or refute the findings in this study.
Topics: Humans; Ameloblastoma; Nigeria; Odontogenic Tumors; Cell Proliferation; Carcinoma
PubMed: 37295743
DOI: 10.1016/j.jormas.2023.101532 -
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 -
Journal of Cancer Research and Clinical... Dec 2023We used proteomic sequencing and experimental verification to identify the potential ferroptosis-related proteins in ameloblastoma.
PURPOSE
We used proteomic sequencing and experimental verification to identify the potential ferroptosis-related proteins in ameloblastoma.
METHODS
Samples of ameloblastoma (n = 14) and normal gingival tissues (n = 5) were collected for proteomic sequencing to identify differentially expressed proteins (DEPs) in ameloblastoma. Ferroptosis-related genes were downloaded from FerrDb V2, which were then compared with DEPs to obtain ferroptosis-related DEPs (FR-DEPs). A functional enrichment analysis was performed, and a protein-protein interaction network was built. The hub proteins were screened using the Cytoscape software, and potential drugs targeting them were retrieved from the DrugBank database. A hub protein was selected for immunohistochemical validation, and its expression was assessed in ameloblastomas, odontogenic keratocysts, dentigerous cysts, and normal gingival tissues. The primary ameloblastoma cells were cultured to explore the effect of the protein on the migratory properties of the tumour cells.
RESULTS
A total of 58 FR-DEPs were screened, and six hub proteins were identified: mTOR, NFE2L2, PRKCA, STAT3, EGFR, and CDH1. Immunohistochemical analysis showed that mTOR expression was upregulated in ameloblastomas compared with that in odontogenic keratocysts, dentigerous cysts, and normal gingival tissues. p-mTOR was highly expressed in ameloblastomas, with a positivity rate of 83.3%. In addition, rapamycin, an inhibitor of mTOR, can inhibit the migratory capacity of primary cultured ameloblastoma cells.
CONCLUSION
Our results revealed the ferroptosis-related proteins in ameloblastomas and their underlying biological processes. Additionally, mTOR was overexpressed and was found to be associated with the aggressiveness of ameloblastomas, which may be a potential target for future treatments.
Topics: Humans; Dentigerous Cyst; Ameloblastoma; Ferroptosis; Proteomics; Immunohistochemistry; Odontogenic Cysts; TOR Serine-Threonine Kinases
PubMed: 37725241
DOI: 10.1007/s00432-023-05412-8 -
Journal of Racial and Ethnic Health... Feb 2024Ameloblastoma is an aggressively growing jaw tumor with high recurrent properties. Reports on global and racial distribution of ameloblastoma are variable and... (Meta-Analysis)
Meta-Analysis Review
Ameloblastoma is an aggressively growing jaw tumor with high recurrent properties. Reports on global and racial distribution of ameloblastoma are variable and inconclusive. The role of race and ethnicity on ameloblastoma growth characteristics, genetic mutational profile, and recurrence is also still unclear. The primary aim of this systematic review was to assess genetic, racial, and ethnic distribution of primary and recurrent ameloblastoma from published literature. The secondary aim was to assess potential correlations between ethnicity, genetic mutation, and disparities in ameloblastoma treatment outcomes in Afro-descendants and non-Afro-descendants. Twenty-three eligible articles were selected based on preferred reporting items for systematic review and meta-analysis (PRISMA), and a total of 169 ameloblastoma cases were evaluated. Data on patient demographics, ameloblastoma growth characteristics, and genetic status were collected for quantitative analysis. Among a total of 169 ameloblastoma cases, Afro-descendant patients had higher primary and recurrent ameloblastomas at 15.5% and 4.7% respectively compared to non-Afro-descendant at 10.7% and 1.8% respectively. Additionally, BRAF V600E was positively associated with 48.8% of all ameloblastomas and strong predilection for Afro-descendants. Despite the paucity of information on genetic profile of ameloblastomas in the Afro-descendant patient cohort, this ethnic group still accounted for 2.95% of all BRAF V600E-positive tumors. These suggest that Afro-descendants are understudied regarding ameloblastoma characteristics, genetic profile, and recurrence profile. Mutational analysis of ameloblastoma tumors in Afro-descendants should be promoted.
Topics: Humans; Ameloblastoma; Proto-Oncogene Proteins B-raf; Jaw Neoplasms; Treatment Outcome; Mutation
PubMed: 36596981
DOI: 10.1007/s40615-022-01500-6