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Indian Journal of Otolaryngology and... Dec 2023Hypoxia-inducible factor-1α is a transcriptional protein that has been extensively researched in human cancers whose overexpression is found to be associated with...
Hypoxia-inducible factor-1α is a transcriptional protein that has been extensively researched in human cancers whose overexpression is found to be associated with unfavorable prognosis. Contemporary studies have proved its vital role in ameloblastoma by correlating its expression with the aggressiveness of the tumor. Therefore, an attempt was made to explore its significance in the malignant transformation and prognosis of ameloblastoma. The present systematic review aimed to understand the impact of HIF-1α in AMB which might lead to favorable outcomes in the treatment. An electronic search was carried out using PubMed, Scopus, Google scholar, Cochrane library, and EMBASE databases. Original articles from all languages involving HIF-1α in AMB were scrutinized by two independent authors. Data were compiled and tabulated in Microsoft Excel and the Risk of bias was analyzed using the JBI tool. Twelve eligible articles were included for the quantitative analysis comprising 305 cases of AMB in which HIF-1α expression was studied for various characteristics like pattern, intensity, and site of immunoexpression which were found to be increased with an increase in the aggressiveness of AMB. It was concluded that HIF-1α is proven to have a crucial role in the progression and aggressiveness of AMB. Extended research regarding the crucial role of HIF-1α in the initiation of tumors and therapies aiming at HIF-1α in AMB cases might show promising outcomes in the future.
PubMed: 37974737
DOI: 10.1007/s12070-023-03928-6 -
Journal of Advanced Veterinary and... Sep 2023The escalating prevalence of canine oral tumors has emerged as a considerable health concern. This study examined the prevalence, types, and distributions of lesions...
OBJECTIVE
The escalating prevalence of canine oral tumors has emerged as a considerable health concern. This study examined the prevalence, types, and distributions of lesions linked to canine oral tumors.
MATERIAL AND METHODS
The medical records of 526 dogs diagnosed with oral tumors were analyzed to determine the prevalence, types, and distributions. Tumor stages were classified into four categories using the tumor node metastasis system.
RESULTS
Among the 526 dogs, there were 118 cases of benign tumors and 408 cases of malignant tumors. Acanthomatous ameloblastoma was the most common benign tumor (43.22%), while melanoma was the most common malignant tumor (51.23%). The gingiva was the most common site for both benign and malignant lesions, accounting for 89.83% and 63.73% of cases, respectively. Melanoma, squamous cell carcinoma, and fibrosarcoma were primarily located in the gingiva, whereas osteosarcoma was commonly found in the mandible. Most tumors were classified as stage III (ranging from 46.84% to 74.58%). Of the reported cases, 56.08% were males and 43.92% were females, and the most common breed was mixed at 30.41%, followed by Poodle at 14.25% and Shih Tzu at 11.40%. Moreover, patients with malignant oral tumors (11.6 ± 3.1 years) were significantly older than those with benign tumors (8.9 ± 3.4 years, < 0.0001).
CONCLUSION
Gingiva was the primary site for oral tumors, and mainly classified as stage III. These findings emphasize the increasing occurrence of oral tumors in senior and geriatric dogs and provide insights into the prevalent types and distribution.
PubMed: 37969809
DOI: 10.5455/javar.2023.j709 -
Neoadjuvant BRAF-targeted therapy for ameloblastoma of the mandible: an organ preservation approach.Journal of the National Cancer Institute Apr 2024Ameloblastoma is a rare odontogenic neoplasm frequently located in the mandible. Standard treatment involves radical bone resection and immediate reconstruction, causing...
BACKGROUND
Ameloblastoma is a rare odontogenic neoplasm frequently located in the mandible. Standard treatment involves radical bone resection and immediate reconstruction, causing functional, aesthetic, and psychological impairments. The BRAF V600E mutation is present in approximately 80% of mandible ameloblastomas, and BRAF inhibitors have demonstrated sustained responses in unresectable cases.
METHODS
We identified ameloblastoma patients planned for ablative surgery and screened them for BRAF V600E mutation. Neoadjuvant BRAF inhibitors were offered to facilitate jaw preservation surgery. Retrospective data collection encompassed treatment regimens, tolerability, tumor response, and conversion to mandible preservation surgery.
RESULTS
Between 2017 and 2022, a total of 11 patients received dabrafenib (n = 6) or dabrafenib with trametinib (n = 5). The median age was 19 (range = 10-83) years. Median treatment duration was 10 (range = 3-20) months. All (100%) patients achieved a radiological response. Ten (91%) patients successfully converted to mandible preservation surgery with residual tumor enucleation. One patient attained complete radiological response, and surgery was not performed. Among the 10 surgically treated patients, all exhibited a pathological response, with 4 achieving near complete response and 6 partial response. At a median follow-up of 14 (range = 7-37) months after surgery, 1 case of recurrence was observed. Grade 1-2 adverse effects were reported in 8 (73%) patients, with a single case of grade 3 (hepatitis). Dose modification was necessary for 3 patients, and 4 experienced treatment interruptions, while 1 patient permanently discontinued therapy.
CONCLUSIONS
Neoadjuvant BRAF inhibition may offer a safe and effective strategy for organ preservation in mandible ameloblastoma treatment.
Topics: Humans; Child; Adolescent; Young Adult; Adult; Middle Aged; Aged; Aged, 80 and over; Ameloblastoma; Proto-Oncogene Proteins B-raf; Neoadjuvant Therapy; Retrospective Studies; Organ Preservation; Mutation; Protein Kinase Inhibitors; Mandible; Imidazoles; Oximes
PubMed: 37966914
DOI: 10.1093/jnci/djad232 -
Case Reports in Oncology 2023Ameloblastic fibrosarcoma (AFS) is considered a malignant progression resulting from dysplastic changes in an ameloblastic fibroma (AF). Both tumors are extremely rare,...
Ameloblastic fibrosarcoma (AFS) is considered a malignant progression resulting from dysplastic changes in an ameloblastic fibroma (AF). Both tumors are extremely rare, with only a few cases reported in the scientific literature. Notably, BRAF mutations have been identified in ameloblastomas, suggesting a connection between ameloblastic morphology and BRAF mutations, as AF is believed to be the precursor neoplasm leading to AFS. In this study, we present a case of AFS in a 25-year-old male. The tumor tissue underwent molecular analysis, specifically next-generation sequencing (NGS) using the Oncomine Comprehensive Assay v3 System. The analysis revealed pathogenic mutations in TP53 and RB genes, as well as copy number gains in NTRK1, MDM4, and BRAF. Additionally, we provide a summary of the literature's findings from the analysis of 107 previously reported AFS cases. Our findings suggest the existence of a molecularly distinct subtype, emphasizing the importance of comprehensive molecular testing for these patients.
PubMed: 37942402
DOI: 10.1159/000532014 -
Cancer Diagnosis & Prognosis 2023Tumors and cysts with odontogenic origin represent a family of lesions with specific histo-genetic and clinical characteristics. Among them, ameloblastomas are common... (Review)
Review
Tumors and cysts with odontogenic origin represent a family of lesions with specific histo-genetic and clinical characteristics. Among them, ameloblastomas are common benign neoplasms, predominantly detected in the anatomic areas of the jaws and also in the mandible and maxilla. Although they are characterized by a slow and stable growing pattern, a subset of them shows a tendency for local tissue invasiveness and partially increased recurrence rates after surgical excision. Furthermore, heat shock proteins (HSPs) are potentially implicated in ameloblastoma onset and progression. HSPs regulate the folding and refolding of proteins and are induced in response to oxidative stress. They are crucial members of the chaperone intracellular system and are categorized based on their molecular weight (i.e., HSP27, HSP60, HSP70, HSP90). In the current review, we describe HSPs origin and function, focusing on their deregulation mechanisms and impact predominantly on ameloblastomas and also on inflammatory and developmental odontogenic cystic lesions.
PubMed: 37927807
DOI: 10.21873/cdp.10265 -
Journal of Oral Pathology & Medicine :... Nov 2023This review aims to analyse the recurrence rate in BRAFv600e+ and BRAFv600e- ameloblastomas and explore its association with clinicopathological variables. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
This review aims to analyse the recurrence rate in BRAFv600e+ and BRAFv600e- ameloblastomas and explore its association with clinicopathological variables.
METHODS
A comprehensive search was conducted using databases including PubMed, Embase, Cochrane Central Register of Controlled Trials, Clinicaltrials.gov, Google Scholar and grey literature, without any limitation on start date or language up to 20 June 2023. A random effect meta-analysis was conducted and Metaregression analyses were performed based on available clinicopathological factors.
RESULTS
Fifteen studies met the criteria for meta-analysis of outcomes. There was no significant difference in overall recurrence rates between the two groups (risk difference = 0.001, p-value = 0.987). Increasing male:female ratio in the BRAFv600e+ group was associated with a lower reported recurrence, suggesting a higher recurrence rate in females. The odds of having mandibular lesion were four times higher in BRAFv600e+ cases compared to BRAFv600e- cases (confidence interval: 2.121-7.870, p < 0.001, I = 28.37%).
CONCLUSION
Within the BRAFv600e+ group, females showed a higher reported recurrence rate. This specific clinical group may benefit from BRAFv600e mutation investigation and potential upscaled surgical treatment and additional BRAF inhibitor therapy, which needs validation in future studies.
Topics: Humans; Male; Female; Ameloblastoma; Proto-Oncogene Proteins B-raf; Mutation; Molecular Targeted Therapy
PubMed: 37872712
DOI: 10.1111/jop.13494 -
Journal of Oral and Maxillofacial... 2023Ameloblastoma (AM) is considered one of the most common lesions of odontogenic origin. Although it is always considered as benign neoplasm, ameloblastic carcinoma (AC)...
Ameloblastoma (AM) is considered one of the most common lesions of odontogenic origin. Although it is always considered as benign neoplasm, ameloblastic carcinoma (AC) represents its malignant counterpart. It is characterized by the expansion of jaws, rapid growth, and a perforated cortex with well-defined unilocular/multilocular radiolucent lesions. To confirm the diagnosis of AM and AC is extremely crucial. Immunohistochemistry such as SOX2 and Ki67 plays a significant role in the confirmation of diagnosis. Management of these cases is from surgical excision with radical neck dissection. The prognosis is poor with only 5 years of survival. This review presents an interesting case of ex-AC, in which the patient was diagnosed at the same site with peripheral AM 1 year ago.
PubMed: 37854922
DOI: 10.4103/jomfp.jomfp_7_23 -
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 -
Journal of Cranio-maxillo-facial... Oct 2023The aim of our study was to review current concepts in targeted therapies for benign tumors of the jaw. Benign odontogenic and maxillofacial bone tumors often require... (Review)
Review
The aim of our study was to review current concepts in targeted therapies for benign tumors of the jaw. Benign odontogenic and maxillofacial bone tumors often require radical surgery, with consequent morbidity that impacts patients' postsurgical quality of life. Currently, targeted therapies and novel nonsurgical therapeutics are being explored for management of non-resectable tumors, with the aim of avoiding surgery or minimizing surgical scope. However, data on clinical applications of targeted therapies for benign tumors of the jaw remain sparse. Therefore, a literature review was conducted, based on the PubMed database, which included in vivo human clinical studies describing clinical application of targeted therapy for benign tumor of the jaw. The review assessed the outcomes of BRAF and MEK inhibitors for treatment of ameloblastoma, RANKL monoclonal antibody for treatment of giant cell tumor, cherubism, aneurysmal bone cyst, and fibrous dysplasia, and tyrosine kinase inhibitor for treatment of odontogenic myxoma and cherubism. Targeted therapies decreased tumor size, slowed down tumor progression, and reduced bone pain. Surgery remains the gold standard, but targeted therapies are promising adjuvant or alternative treatment options for reducing tumor progression and morbidity of tumor surgery.
Topics: Humans; Jaw Neoplasms; Cherubism; Quality of Life; Odontogenic Tumors; Ameloblastoma
PubMed: 37852890
DOI: 10.1016/j.jcms.2023.10.003 -
Journal of Oral Pathology & Medicine :... Nov 2023CTNNB1 gene encodes beta catenin, a transcriptional activator of Wnt pathway involved in the pathogenesis of odontogenic lesions. Though located intramembranously, its... (Review)
Review
BACKGROUND
CTNNB1 gene encodes beta catenin, a transcriptional activator of Wnt pathway involved in the pathogenesis of odontogenic lesions. Though located intramembranously, its translocation into cytoplasm and nucleus could trigger cell proliferation, inhibition of apoptosis, invasion and migration of the tumour cell.
MATERIALS AND METHODS
Five electronic databases including MEDLINE by PubMed, Google scholar, Scopus, Trip, Cochrane library and EMBASE until 1 January 2023 without period restriction were thoroughly searched. Those articles that identified CTNNB1 mutation and beta catenin in odontogenic lesions were included for review. Risk of bias was analysed for each study using QUADAS 2 tool and Review Manager 5.3 was used to output its result.
RESULTS
Thirty four published articles were included for data synthesis. A total of 1092 cases of odontogenic lesions were assessed for both CTNNB1 mutation and beta catenin expression. CTNNB1 mutation was observed in ameloblastoma, calcifying odontogenic cyst, calcifying cystic odontogenic tumour and all malignant odontogenic tumours. The beta catenin expression (nuclear and cytoplasmic) was maximum in odontogenic keratocyst and calcifying odontogenic cyst. The expression was variable in ameloblastomas, membranous in odontomas, calcifying cystic odontogenic tumour and nuclear in all malignant tumours.
DISCUSSION AND CONCLUSION
High recurrence of odontogenic keratocyst and aggressiveness of solid ameloblastoma and malignant odontogenic tumours could be associated with the nuclear translocation of beta catenin. Disparity between CTNNB1 mutation and beta catenin expression within odontogenic lesions suggests alternate routes of beta catenin activation. The review results support the unique localisation of beta catenin as a helpful diagnostic factor in the pathogenesis of odontogenic lesions.
Topics: Humans; Ameloblastoma; beta Catenin; Odontogenic Cyst, Calcifying; Odontogenic Cysts; Odontogenic Tumors
PubMed: 37840228
DOI: 10.1111/jop.13487