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International Journal of Clinical and... 2018Ameloblastoma shows invasive growth and is susceptible to recurrence. This study aimed to detect the expression of E-Cadherin, Vimentin and β-Catenin (proteins related...
OBJECTIVE
Ameloblastoma shows invasive growth and is susceptible to recurrence. This study aimed to detect the expression of E-Cadherin, Vimentin and β-Catenin (proteins related to epithelial mesenchymal transformation (EMT) in the ameloblastoma and to explore association with clinicopathological characteristics of ameloblastoma.
METHODS
Immunohistochemistry was employed to detect the protein expression of E-Cadherin, Vimentin and β-Catenin in the ameloblastoma, and its association with clinicopathological characteristics of ameloblastoma was further evaluated.
RESULTS
E-Cadherin expression was reduced or absent on the membrane of the peripheral columnar and cubic epithelial cells; Vimentin expression was high in the interstitium as well as epithelial cells in ameloblastoma; E-Cadherin expression was negatively related to Vimentin expression. β-catenin expression on the membrane of ameloblastoma epithelial cells reduced, but its ectopic expression was observed in the cytoplasm and/or nucleus.
CONCLUSION
EMT related proteins E-Cadherin, β-catenin and Vimentin are involved in the occurrence and development of ameloblastoma and these proteins can be used as biomarkers of invasiveness of ameloblastoma.
PubMed: 31938101
DOI: No ID Found -
Journal of Dental Research Nov 2022Ameloblastoma (AB) is an odontogenic tumor that arises from ameloblast-lineage cells. Although relatively uncommon and rarely metastatic, AB tumors are locally invasive...
Ameloblastoma (AB) is an odontogenic tumor that arises from ameloblast-lineage cells. Although relatively uncommon and rarely metastatic, AB tumors are locally invasive and destructive to the jawbone and surrounding structures. Standard-of-care surgical resection often leads to disfigurement, and many tumors will locally recur, necessitating increasingly challenging surgeries. Recent genomic studies of AB have uncovered oncogenic driver mutations, including in the mitogen-activated protein kinase (MAPK) and Hedgehog signaling pathways. Medical therapies targeting those drivers would be a highly desirable alternative or addition to surgery; however, a paucity of existing AB cell lines has stymied clinical translation. To bridge this gap, here we report the establishment of 6 new AB cell lines-generated by "conditional reprogramming"-and their genomic characterization that reveals driver mutations in FGFR2, KRAS, NRAS, BRAF, PIK3CA, and SMO. Furthermore, in proof-of-principle studies, we use the new cell lines to investigate AB oncogene dependency and drug sensitivity. Among our findings, AB cells with KRAS or NRAS mutation (MAPK pathway) are exquisitely sensitive to MEK inhibition, which propels ameloblast differentiation. AB cells with activating SMO-L412F mutation (Hedgehog pathway) are insensitive to vismodegib; however, a distinct small-molecule SMO inhibitor, BMS-833923, significantly reduces both downstream Hedgehog signaling and tumor cell viability. The novel cell line resource enables preclinical studies and promises to speed the translation of new molecularly targeted therapies for the management of ameloblastoma and related odontogenic neoplasms.
Topics: Humans; Ameloblastoma; Hedgehog Proteins; Proto-Oncogene Proteins B-raf; Proto-Oncogene Proteins p21(ras); Neoplasm Recurrence, Local; Odontogenic Tumors; Class I Phosphatidylinositol 3-Kinases; Mitogen-Activated Protein Kinases; Mitogen-Activated Protein Kinase Kinases; Cell Line
PubMed: 35689405
DOI: 10.1177/00220345221100773 -
Medical Oncology (Northwood, London,... Apr 2023Ameloblastoma in 66% of the cases harbor a somatic mutation of the "mitogen-activated protein kinase" signaling pathway (BRAF V600E). In V600E mutations, BRAF is in the... (Review)
Review
BACKGROUND
Ameloblastoma in 66% of the cases harbor a somatic mutation of the "mitogen-activated protein kinase" signaling pathway (BRAF V600E). In V600E mutations, BRAF is in the permanent "on" state and relays the growth-promoting signals independently of the EGFR pathway. Therefore, mutant BRAF represents a target for handful of new drugs.
METHODS
We conducted a literature search, with the search terms "Vemurafenib, Dabrafenib, Ameloblastoma, and BRAF." These included seven case reports with nine patients who underwent monotherapy with Dabrafenib or Vemurafenib or combination therapy with Dabrafenib and Trametinib.
RESULTS
The patients age ranges from 10 years up to 86 years. The distribution of women and men is 4:5. Patients with an initial diagnosis of ameloblastoma, as well as recurrences or metastasized ameloblastoma were treated. Indications cover neoadjuvant therapy up to the use in metastasized patients in an irresectable state. Results ranging from "only" tumor size reduction to restitutio ad integrum.
CONCLUSION
We see the use of BRAF Inhibitors to reduce tumor size with consecutive surgical treatment as a reasonable option for therapy. However, we are aware that at present the data are based only on case reports with the longest follow-up of just 38 months. We encourage further clinical trials in the use of BRAF Inhibitors for selecting ameloblastoma patients in a multi-center setting.
Topics: Male; Humans; Female; Child; Vemurafenib; Proto-Oncogene Proteins B-raf; Ameloblastoma; Imidazoles; Protein Kinase Inhibitors; Mutation; Antineoplastic Combined Chemotherapy Protocols
PubMed: 37115331
DOI: 10.1007/s12032-023-01993-z -
Head & Face Medicine Jul 2021Aberrant expression of stem cell markers has been observed in several types of neoplasms. This trait attributes to the acquired stem-like property of tumor cells and can...
BACKGROUND
Aberrant expression of stem cell markers has been observed in several types of neoplasms. This trait attributes to the acquired stem-like property of tumor cells and can impact patient prognosis. The objective of this study was to comparatively analyze the expression and significance of SOX2 and OCT4 in various types of odontogenic cysts and tumors.
METHODS
Fifty-five cases of odontogenic cysts and tumors, including 15 ameloblastomas (AM), 5 adenomatoid odontogenic tumors (AOT), 5 ameloblastic fibromas (AF), 5 calcifying odontogenic cysts (COC), 10 dentigerous cysts (DC) and 15 odontogenic keratocysts (OKC) were investigated for the expression of SOX2 and OCT4 immunohistochemically.
RESULTS
Most OKCs (86.7 %) and all AFs expressed SOX2 in more than 50 % of epithelial cells. Its immunoreactivity was moderate-to-strong in all epithelial cell types in both lesions. In contrast, SOX2 expression was undetectable in AOTs and limited to the ameloblast-like cells in a minority of AM and COC cases. Most DCs showed positive staining in less than 25 % of cystic epithelium. Significantly greater SOX2 expression was noted in OKC compared with DC or AM, and in AF compared with COC or AOT. OCT4 rarely expressed in odontogenic lesions with the immunoreactivity being mild and present exclusively in OKCs.
CONCLUSIONS
SOX2 is differentially expressed in odontogenic cysts and tumors. This could be related to their diverse cells of origin or stages of histogenesis. The overexpression of SOX2 and OCT4 in OKC indicates the acquired stem-like property. Future studies should investigate whether the overexpression of OCT4 and SOX2 contributes to the aggressive behaviors of the tumors.
Topics: Ameloblastoma; Humans; Odontogenic Cysts; Odontogenic Tumors; SOXB1 Transcription Factors; Stem Cells
PubMed: 34261507
DOI: 10.1186/s13005-021-00283-1 -
Journal of Dental Research Jan 2019BRAF V600E is the most common mutation in conventional ameloblastoma (AM) of the mandible. In contrast, maxillary AMs appear to harbor more frequently RAS, FGFR2, or SMO...
BRAF V600E is the most common mutation in conventional ameloblastoma (AM) of the mandible. In contrast, maxillary AMs appear to harbor more frequently RAS, FGFR2, or SMO mutations. Unicystic ameloblastoma (UAM) is considered a less aggressive variant of ameloblastoma, amenable to more conservative treatment, and classified as a distinct entity. The aim of this study was to characterize the mutation profile of UAM ( n = 39) and to compare it to conventional AM ( n = 39). The associations between mutation status and recurrence probability were also analyzed. In the mandible, 94% of UAMs (29/31, including 8/8 luminal, 6/8 intraluminal, and 15/15 mural subtypes) and 74% of AMs (28/38) revealed BRAF V600E mutations. Among the BRAF wild-type cases, 1 UAM showed a missense SMO mutation (p.L412F), whereas 2 NRAS (p.Q61R), 2 HRAS (p.Q61R), and 2 FGFR2 (p.C383R) activating mutations were identified in AM. Of the 3 maxillary UAMs, only 1 revealed a BRAF V600E mutation. Taken together, our findings demonstrate high frequency of activating BRAF V600E mutations in both UAM and AM of the mandible. In maxillary UAMs, the BRAF V600E mutation prevalence appears to be lower as was shown for AM previously. It could therefore be argued that UAM and AM are part of the spectrum of the same disease. AMs without BRAF V600E mutations were associated with an increased rate of local recurrence ( P = 0.0003), which might indicate that routine mutation testing also has an impact on prognosis.
Topics: Ameloblastoma; Genetic Markers; Humans; Jaw Neoplasms; Mitogen-Activated Protein Kinase Kinases; Mutation; Neoplasm Recurrence, Local; Odontogenic Tumors; Prognosis; Proto-Oncogene Proteins B-raf
PubMed: 30216733
DOI: 10.1177/0022034518798810 -
European Annals of Otorhinolaryngology,... Feb 2017Ameloblastoma is a rare, benign odontogenic tumour associated with a high recurrence rate. It accounts for 1% of all tumours of the jaws. The purpose of this study was...
INTRODUCTION
Ameloblastoma is a rare, benign odontogenic tumour associated with a high recurrence rate. It accounts for 1% of all tumours of the jaws. The purpose of this study was to compare the ameloblastoma recurrence rate according to the type of treatment: radical or conservative.
PATIENTS AND METHODS
All patients with a diagnosis of ameloblastoma between 1991 and 2013 were retrospectively identified in order to extract topographic, radiological, and histological data and the type of treatment: conservative (marsupialization, enucleation, curettage) or radical (segmental resection) and to compare the recurrence rate according to the type of treatment.
RESULTS
Twenty-seven patients were included, managed by conservative treatment (CT) in 22 cases and radical treatment (RT) in 14 cases. The recurrence rate was 90.9% in the CT group and 9.1% in the RT group (P=0.025) with a mean follow-up of 56.2 months.
DISCUSSION
The recurrence rate after conservative treatment was higher than that after radical treatment. These results are similar to those reported in the literature. The choice of treatment must be adapted to the macroscopic and histological characteristics of each tumour and to the patient.
Topics: Ameloblastoma; Conservative Treatment; Female; Follow-Up Studies; Humans; Jaw Neoplasms; Male; Middle Aged; Neoplasm Recurrence, Local; Retrospective Studies
PubMed: 27793625
DOI: 10.1016/j.anorl.2016.09.004 -
Journal of Dental Research Feb 2015
Review
Topics: Ameloblastoma; Hedgehog Proteins; Humans; MAP Kinase Signaling System; Molecular Targeted Therapy; Mutation; Proto-Oncogene Proteins B-raf
PubMed: 25425580
DOI: 10.1177/0022034514560373 -
Scientific Reports Sep 2021Ameloblastomas are odontogenic tumors that are rare in people but have a relatively high prevalence in dogs. Because canine acanthomatous ameloblastomas (CAA) have... (Comparative Study)
Comparative Study
Ameloblastomas are odontogenic tumors that are rare in people but have a relatively high prevalence in dogs. Because canine acanthomatous ameloblastomas (CAA) have clinicopathologic and molecular features in common with human ameloblastomas (AM), spontaneous CAA can serve as a useful translational model of disease. However, the molecular basis of CAA and how it compares to AM are incompletely understood. In this study, we compared the global genomic expression profile of CAA with AM and evaluated its dental origin by using a bulk RNA-seq approach. For these studies, healthy gingiva and canine oral squamous cell carcinoma served as controls. We found that aberrant RAS signaling, and activation of the epithelial-to-mesenchymal transition cellular program are involved in the pathogenesis of CAA, and that CAA is enriched with genes known to be upregulated in AM including those expressed during the early stages of tooth development, suggesting a high level of molecular homology. These results support the model that domestic dogs with spontaneous CAA have potential for pre-clinical assessment of targeted therapeutic modalities against AM.
Topics: Ameloblastoma; Animals; Carcinoma, Squamous Cell; Dog Diseases; Dogs; Epithelial-Mesenchymal Transition; Gene Expression Profiling; Genes, ras; Gingiva; Humans; Jaw Neoplasms; MAP Kinase Signaling System; Multigene Family; Mutation; Neoplasm Proteins; Proto-Oncogene Proteins B-raf; Proto-Oncogene Proteins p21(ras); RNA, Messenger; RNA, Neoplasm; RNA-Seq; Signal Transduction; Species Specificity; Transcriptome
PubMed: 34493785
DOI: 10.1038/s41598-021-97430-0 -
Journal of Oral and Maxillofacial... 2016Ameloblastoma is the second most common odontogenic tumor after odontoma which occurs exclusively in the jaws and very rarely in the sinonasal cavities.
CONTEXT
Ameloblastoma is the second most common odontogenic tumor after odontoma which occurs exclusively in the jaws and very rarely in the sinonasal cavities.
AIMS
The aim of the study was to determine the demographic and histopathological variations of ameloblastoma in Eastern Indian population by retrospectively comparing and evaluating diagnosed cases of ameloblastoma using different parameters.
MATERIALS AND METHODS
Histopathologically diagnosed cases of ameloblastoma retrieved from past records of the Department of Oral Pathology were selected for the study. Totally, 148 cases were isolated from record of previous 7 years. The patients were divided according to (a) gender, (b) age group, (c) site of the lesion and (d) histopathological types. The findings of this study were compared with those available in literature.
STATISTICAL ANALYSIS USED
This is a retrospective study, mean and standard deviation was calculated.
RESULTS
Among 148 patients, 88 (59.45%) were male and 60 (40.55%) were female. A maximum number of cases (101 of 148) of ameloblastoma were found in the second to fourth decades of life. Mandiblular posterior region was commonly involved (48.6%). Solid/multicystic variety was found in 63.1% followed by unicystic with 21.5%. We found one case each of extraosseous and desmoplastic ameloblastoma. It was difficult for panel of experienced oral pathologists to pinpoint the exact type in 15 (10%) cases, this was due to mixture of follicular and plexiform variety with equal presence of both types of architecture, without predominance of any variety in particular.
CONCLUSIONS
These data may serve as baseline information on occurrence of various histopathological types of ameloblastoma in Eastern Indian population and helps comparing it with other similar studies conducted in different geographic population.
PubMed: 27601814
DOI: 10.4103/0973-029X.185937 -
Indian Journal of Dental Research :... 2023Ameloblastoma is a benign, locally aggressive neoplasm that constitutes about 1-3% of the tumors of the jaw. Wide surgical excision with adequate safe margin is the most...
Ameloblastoma is a benign, locally aggressive neoplasm that constitutes about 1-3% of the tumors of the jaw. Wide surgical excision with adequate safe margin is the most common treatment of choice. The study aimed to manage cases with unicystic ameloblastoma while preserving the continuity of the mandible (without resection). This article presents a series of cases ranging from 18 to 40 years old patients of both sexes with unicystic ameloblastoma, especially in the mandible showing more male predilection than female. All the cases presented in this article were treated by enucleation and curettage. None of the patients presented post-operative paresthesia. None of the cases went in for resection. Post-operative recovery was uneventful in all the patients. All the patients were followed up for a period of 3.5-5 years. None of the cases reported recurrence at the date of publication.
Topics: Humans; Male; Female; Adolescent; Young Adult; Adult; Ameloblastoma; Mandibular Neoplasms; Neoplasm Recurrence, Local; Mandible; Research
PubMed: 37417069
DOI: 10.4103/ijdr.ijdr_521_22