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Journal of Personalized Medicine Jan 2022Ameloblastoma is the most common benign odontogenic neoplasm, but with an aggressive behavior and a high recurrence rate. Nowadays wide surgical resection is the current...
Ameloblastoma is the most common benign odontogenic neoplasm, but with an aggressive behavior and a high recurrence rate. Nowadays wide surgical resection is the current recommended treatment, which can cause further loss of function and esthetics. Recent studies point to the stem/progenitor cells as both initiators and propagators of the tumors. Elucidation of the cellular and molecular mechanisms underlying the tumor stem cells is of broad interest for understanding tumorigenesis and for developing effective targeted therapies. SRY related HMG box gene 2 (SOX2) is a transcription factor that plays important roles in development, stem cell renewal, and cancer formation. Few studies have revealed increased SOX2 expression in atypical ameloblastoma and ameloblastic carcinoma. For the development of personalized medicine for ameloblastoma, biomarkers that provide prognostic or predictive information regarding a tumor's nature or its response to treatment are essential. Thus, in this study, we aimed to study if SOX2-positive cells exist in ameloblastomas and their correlation with the clinicopathologic parameters. Our data suggested BRAF(V600E) mutation might contribute to the expansion of SOX2-positive cells. The identification of BRAF(V600E) mutation and the amplification of SOX2-positive cells in ameloblastomas imply the possible benefit of applying BRAF and SOX2 inhibitors in recurrent and un-resectable ameloblastomas.
PubMed: 35055392
DOI: 10.3390/jpm12010077 -
World Journal of Clinical Oncology Jan 2020Ameloblastomas are common benign epithelial odontogenic neoplasms that present an aggressive and unpredictable behavior that may modify treatment strategies. Different...
BACKGROUND
Ameloblastomas are common benign epithelial odontogenic neoplasms that present an aggressive and unpredictable behavior that may modify treatment strategies. Different signaling pathways that participate in the progression of these tumors have been identified. B-raf proto-oncogene serine/threonine kinase (BRAF) is a protein involved in the behavior of ameloblastomas, and it is related to many cell mechanisms. BRAF gene mutations have been identified in ameloblastomas, of which the BRAF V600E (valine substituted by glutamic acid at amino acid 600) mutation has been the most common and can be present concomitantly with other mutations that may be involved in its behavior. Targeted therapies have been used as an alternative in the case of resistance or contraindications to conventional treatments.
AIM
To document the presence of BRAF V600E and additional mutations, their behavior, and targeted therapies in these tumors.
METHODS
An electronic literature search was conducted according to PRISMA guidelines in PubMed/MEDLINE, Cochrane, EMBASE, and SpringerLink using the terms "ameloblastomas", "BRAF V600E", "additional mutations", and "targeted therapies". Ameloblastomas were classified according to WHO guidelines. Inclusion criteria were articles in English, published not more than 10 years ago, and studies with laboratory works related to BRAF V600E. Articles were evaluated by two independent reviewers and retrieved for full-text evaluation. The EBLIP Critical Appraisal Checklist was used to evaluate the quality of the eligible studies. Descriptive statistical analysis was performed.
RESULTS
Two independent reviewers, with a substantial concordance indicated by a kappa coefficient of = 0.76, evaluated a total of 19 articles that were included in this study. The analysis registered 521 conventional ameloblastomas (AM), 81 unicystic ameloblastomas (UA), 13 ameloblastic carcinomas (AC), three metastatic ameloblastomas (MA), and six peripheral ameloblastomas (PA), of which the histopathological type, anatomic location, laboratory tests, expression of BRAF mutation, and additional mutations were registered. The BRAF V600E mutation was found in 297 AM (57%), 63 UA (77.7%), 3 AC (23%), 1 MA (50%), and 5 PA (83.3%). Follicular type predominated with a total of 116 cases (40%), followed by plexiform type with 63 cases (22.1%). Furthermore, both types presented additional mutations, in which alterations in JAK3 P132T, SMARCB1, PIK3CA, CTNNB1, SMO, and BRAF G606E genes were found. Four case reports were found with targeted therapy to BRAF V600E.
CONCLUSION
The identification of BRAF V600E and additional mutations as an aid in targeted therapies has been a breakthrough in alternative treatments of ameloblastomas where surgical treatments are contraindicated.
PubMed: 31976308
DOI: 10.5306/wjco.v11.i1.31 -
World Journal of Surgical Oncology Feb 2020Primary intraosseous carcinoma (PIOC), NOS is an odontogenic carcinoma with unknown etiology. Its diagnosis may be used when central jaw carcinoma cannot be categorized...
BACKGROUND
Primary intraosseous carcinoma (PIOC), NOS is an odontogenic carcinoma with unknown etiology. Its diagnosis may be used when central jaw carcinoma cannot be categorized as any other type of carcinoma. Further information on this extremely rare tumor is needed to improve our understanding and evaluate the classification of odontogenic carcinomas.
CASE PRESENTATION
We herein presented two patients with PIOC, NOS with different clinical and histopathological features and analyzed gene mutations in these patients using next-generation sequencing (NGS). The typical PIOC, NOS case had many histopathological similarities to oral squamous cell carcinoma (OSCC), including the missense point mutations of TP53 Glu285Val, KDR Gln472His, and APC Pro1433Leu, which are similar to those in other cancers; however, no mutations were detected in the other patient with an atypical presentation of PIOC, NOS, which was derived from a precursor cystic lesion with similarities to both ameloblastic carcinoma and OSCC.
CONCLUSIONS
Genetic analysis suggested that these two PIOC, NOS cases have different features and can be subcategorized.
Topics: Adult; Aged; Ameloblastoma; Carcinoma, Squamous Cell; Humans; Jaw Neoplasms; Male; Mouth Neoplasms; Mutation; Odontogenic Tumors
PubMed: 32113465
DOI: 10.1186/s12957-020-01827-6 -
Ameloblastic Carcinoma with Calcification: A Rare Case Report in the Mandible and Literature Review.Case Reports in Dentistry 2020Ameloblastic carcinoma (AC) is a scarce malignant tumor which is more prevalent in the mandible than the maxilla. It occurs in a wide range of age groups, and there is a...
Ameloblastic carcinoma (AC) is a scarce malignant tumor which is more prevalent in the mandible than the maxilla. It occurs in a wide range of age groups, and there is a sex predilection in males. AC shows specific microscopic features and requires more aggressive surgical treatment plans in comparison with conventional ameloblastoma. Radiographically, AC resembles ameloblastoma except that it rarely represents focal mineralized materials, seemingly reflecting dystrophic calcification. This characteristic is uncommon in typical ameloblastomas, and only few cases reported with such opacities and mineralized materials. Due to this rare radiographic and microscopic presentation, an accurate diagnosis could be challenging, and pathologists should consider a combination of benign and malignant odontogenic tumors occurring in jaws.
PubMed: 33110663
DOI: 10.1155/2020/4216489 -
Journal of Oral Science 2016The Wilms' tumor 1 gene (WT1) was originally isolated and described as the gene responsible for Wilms' tumor. Although there is growing evidence linking the...
The Wilms' tumor 1 gene (WT1) was originally isolated and described as the gene responsible for Wilms' tumor. Although there is growing evidence linking the overexpression of WT1 to tumorigenesis, no reports on ameloblastoma are available at present. The aim of this study was to examine the expression of WT1 in various histological subtypes of ameloblastoma tissue specimens and in human ameloblastoma cell lines. Immunohistochemical analyses were performed on a total of 168 cases of ameloblastoma, one case of ameloblastic carcinoma, and five cases of tooth germs (control). Three immortalized human dental epithelial cell lines (HAM1, HAM2, and HAM3) derived from the same ameloblastoma patient were used for reverse transcription-polymerase chain reaction (RT-PCR) and western blot assays. The tooth germs did not express WT1 (0%), and more than half of the ameloblastoma cases showed WT1 overexpression (54.7%). Immunoreactivity of solid-type ameloblastoma (76.1%) was more evident than that of unicystic-type ameloblastoma (40.9%). The expression level of WT1 mRNA in HAM2 was higher than that in HAM1 (moderate) and HAM3 (weak), showing the heterogeneity of tumor cells. The WT1 protein was strongly detected in HAM2 and minimally detected in HAM1 and HAM3. Our results suggest that WT1 expression influences the pathogenesis of ameloblastoma by varying its expression level in different histological types. (J Oral Sci 58, 407-413, 2016).
Topics: Ameloblastoma; Cell Line, Transformed; Gene Expression; Humans; Wilms Tumor
PubMed: 27665981
DOI: 10.2334/josnusd.15-0546 -
Cureus Dec 2019Ameloblastic carcinoma (AC) is an exceedingly rare odontogenic cancer about which there is limited information in the literature. We present a case of AC originating in...
Ameloblastic carcinoma (AC) is an exceedingly rare odontogenic cancer about which there is limited information in the literature. We present a case of AC originating in the sinus cavity and extending to the skull base in a patient in the first trimester of pregnancy. Diagnostic work up was complicated by this pregnancy, which delayed radiation exposure with imaging. Once scans were obtained, diagnosis was further complicated by the radiographic similarities between possible lung metastases and previously undiagnosed sarcoid nodules. After thorough work up to rule out metastatic disease, the patient was successfully treated with primary surgical resection followed by adjuvant chemoradiation. The patient remained disease free at one year after therapy. This case demonstrates the importance of thorough work up in the diagnosis of AC, and is an opportunity to review the literature and discuss therapeutic methods to treat this rare, aggressive neoplasm.
PubMed: 31903302
DOI: 10.7759/cureus.6265 -
Journal of Clinical and Diagnostic... Oct 2016Malignant odontogenic tumours are rare and represent approximately 1% of all oral malignancies. Ameloblastic carcinoma is a rare odontogenic tumour, which is aggressive...
Malignant odontogenic tumours are rare and represent approximately 1% of all oral malignancies. Ameloblastic carcinoma is a rare odontogenic tumour, which is aggressive in nature with extensive local bone destruction that has retained the features of ameloblastic differentiation and also exhibits cytological features of malignancy. It occurs primarily in the mandible in a wide range of age groups. It may arise de-novo or in pre-existing ameloblastoma or odontogenic cyst. The purpose of this report is to present three cases of ameloblastic carcinoma with varying presentations as central and peripheral entities.
PubMed: 27891485
DOI: 10.7860/JCDR/2016/21100.8697 -
Cancer Medicine Dec 2019Ameloblastic carcinoma (AC) is defined as a rare primary epithelial odontogenic malignant neoplasm and the malignant counterpart of benign epithelial odontogenic tumor...
Ameloblastic carcinoma (AC) is defined as a rare primary epithelial odontogenic malignant neoplasm and the malignant counterpart of benign epithelial odontogenic tumor of ameloblastoma (AB) by the WHO classification. AC develops pulmonary metastasis in about one third of the patients and reveals a poor prognosis. However, the mechanisms of AC oncogenesis remain unclear. In this report, we aimed to clarify the mechanisms of malignant transformation of AB or AC carcinogenesis. The relatively important genes in the malignant transformation of AB were screened by DNA microarray analysis, and the expression and localization of related proteins were examined by immunohistochemistry using samples of AB and secondary AC. Two genes of hypoxia-inducible factor 1 alpha subunit (HIF1A) and zinc finger E-box-binding homeobox 1 (ZEB1) were significantly and relatively upregulated in AC than in AB. Both genes were closely related in hypoxia and epithelial-mesenchymal transition (EMT). In addition, expressions of HIF-1α and ZEB1 proteins were significantly stronger in AC than in AB. In the cell assays using ameloblastoma cell line, AM-1, hypoxia condition upregulated the expression of transforming growth factor-β (TGF-β) and induced EMT. Furthermore, the hypoxia-induced morphological change and cell migration ability were inhibited by an antiallergic medicine tranilast. Finally, we concluded that hypoxia-induced HIF-1α and ZEB1 were critical for the malignant transformation of AB via TGF-β-dependent EMT. Then, both HIF-1α and ZEB1 could be potential biomarkers to predict the malignant transformation of AB.
Topics: Adolescent; Adult; Aged; Ameloblastoma; Cell Line, Tumor; Cell Transformation, Neoplastic; Epithelial-Mesenchymal Transition; Female; Gene Expression Profiling; Humans; Hypoxia; Hypoxia-Inducible Factor 1, alpha Subunit; Immunohistochemistry; Male; Middle Aged; Transforming Growth Factor beta; Young Adult; Zinc Finger E-box-Binding Homeobox 1
PubMed: 31674718
DOI: 10.1002/cam4.2667 -
Cureus Nov 2023Ameloblastoma is a benign yet locally aggressive tumor of the jaw bones and is most commonly found in the lower mandibular region. Histologically, it shows benign...
Ameloblastoma is a benign yet locally aggressive tumor of the jaw bones and is most commonly found in the lower mandibular region. Histologically, it shows benign characteristics. However, ameloblastoma can turn malignant to show a more aggressive clinical course. Carcinoma ex ameloblastoma is an extremely rare malignancy arising from a pre-existing long-standing ameloblastoma or a recurrence of an ameloblastoma. According to the literature search, six to seven cases have so far been documented, and the majority of the lesions had a propensity to metastasize. Here, we present a case of carcinoma ex ameloblastoma implicating a 19-year-old male patient manifesting in the mandible, which arises from pre-existing ameloblastoma.
PubMed: 38156168
DOI: 10.7759/cureus.49536 -
Journal of the Korean Association of... Feb 2016Ameloblastic carcinoma is a malignant form of ameloblastoma defined by histological evidence of malignancy in primary, recurrent, or metastatic tumor. Such a tumor is...
Ameloblastic carcinoma is a malignant form of ameloblastoma defined by histological evidence of malignancy in primary, recurrent, or metastatic tumor. Such a tumor is rare, and the maxilla is an unusual site. Due to its rarity, the characteristics of this tumor in the maxilla have not been well described. Case 1: A 55-year-old, ill-appearing Nigerian male presented to our center with left maxillary swelling of seven-year duration. The swelling had been slow-growing and painless until one year prior, when the growth became rapid and was coupled with severe pain. The swelling affected both oral function and facial esthetics, and the patient reported difficulty breathing. There was a maxillary, ulcerated swelling extending from teeth 12 to 18 and blocking the left nostril. The involved teeth were moderately mobile. Case 2: A 32-year-old male farmer presented with recurrent right maxillary swelling of six-year duration. Prior to this episode, he had undergone surgery for ameloblastoma (follicular type). The present swelling was fungating through the skin and protruding into the right nostril. Ameloblastic carcinoma is an aggressive odontogenic tumor that requires aggressive surgical treatment.
PubMed: 26904494
DOI: 10.5125/jkaoms.2016.42.1.43