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1.
Artigo em Inglês | MEDLINE | ID: mdl-38324239

RESUMO

Ameloblastoma is a highly recurrent odontogenic neoplasm with variable global distribution. However, impact of race and ethnicity on ameloblastoma recurrence are still unclear. The primary aim of this study was to assess duration of time between primary and recurrent ameloblastomas in a predominantly Black multi-institutional patient cohort and secondarily to determine whether recurrent ameloblastomas are more readily discovered when clinically-symptomatic rather than by radiographic surveillance. A retrospective cross-sectional design was used to evaluate demographic, clinical, and pathological information on recurrent ameloblastomas patients. Outcome variable was time to recurrence, determined as period between the diagnosis of primary and recurrent ameloblastomas. We assessed associations between outcome variable and race, time lapse between primary and recurrent ameloblastomas and clinical symptoms of recurrent ameloblastomas at time of diagnosis. Among 115 recurrent ameloblastomas identified, 90.5% occurred in adults, 91.3% in Blacks, and similarly, 91.3% were conventional ameloblastomas. About 41% affected the posterior mandible. 93.9% were clinically symptomatic at time of presentation while 6.1% non-symptomatic lesions were discovered by routine diagnostic radiology. Median time to presentation of recurrent tumor was significantly longer in females (90 months, p = 0.016) and clinically symptomatic group of ameloblastoma patients (75 months, p = 0.023). Ameloblastoma recurrence was distinctively high in Black patients, occurred faster in males than females and was located mostly in the posterior mandible. Concomitant with delayed access to healthcare of Black individuals, routine post-surgical follow-up is essential because time lag between primary and recurrence tumors was longer in clinically symptomatic ameloblastomas at the time of diagnosis.

2.
J Oral Pathol Med ; 53(1): 79-87, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38185471

RESUMO

BACKGROUND: Ameloblastoma is an aggressively growing, highly recurrent odontogenic jaw tumor. Its association with BRAFV600E mutation is an indication for BRAFV00E-inhibitor therapy The study objective was to identify a sensitive low-cost test for BRAFV600E-positive ameloblastoma. We hypothesized that immunohistochemical staining of formalin-fixed paraffin-embedded tissues for BRAFV600E mutation is a low-cost surrogate for BRAFV600E gene sequencing when laboratory resources are inadequate for molecular testing. METHODS: Tissues from 40 ameloblastoma samples were retrieved from either formalin-fixed paraffin-embedded blocks, RNAlater™ stabilization solution or samples inadvertently pre-fixed in formalin before transfer to RNAlater™. BRAFV600E mutation was assessed by Direct Sanger sequencing, Amplification Refractory Mutation System-PCR and immunohistochemistry (IHC). RESULTS: BRAFV600E mutation was detected by IHC, Amplification Refractory Mutation System-PCR and Direct Sanger sequencing in 93.33%, 52.5% and 30% of samples respectively. Considering Direct Sanger sequencing as standard BRAFV600E detection method, there was significant difference between the three detection methods (𝜒2 (2) = 31.34, p < 0.0001). Sensitivity and specificity of IHC were 0.8 (95% CI: 0.64-0.90) and 0.9 (95% CI: 0.75-0.99) respectively, while positive predictive value and negative predictive value (NPV) were 0.9 and 0.8 (Fischer's test, p < 0.0001) respectively. Sensitivity and specificity of Amplification Refractory Mutation System-PCR detection method were 0.7 (95% CI: 0.53-0.80) and 0.9 (95% CI = 0.67-0.98) respectively, while PPV and NPV were 0.9 and 0.6 respectively (Fischer's test, p < 0.0001). CONCLUSION: Low-cost and less vulnerability of IHC to tissue quality make it a viable surrogate test for BRAFV600E detection in ameloblastoma. Sequential dual IHC and molecular testing for BRAFV600E will reduce equivocal results that could exclude some patients from BRAFV600E-inhibitor therapies.


Assuntos
Ameloblastoma , Tumores Odontogênicos , Humanos , Ameloblastoma/diagnóstico , Ameloblastoma/genética , Ameloblastoma/patologia , Proteínas Proto-Oncogênicas B-raf/genética , Mutação , Tumores Odontogênicos/genética , Formaldeído
3.
J Racial Ethn Health Disparities ; 11(1): 92-100, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36596981

RESUMO

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.


Assuntos
Ameloblastoma , Neoplasias Maxilomandibulares , Humanos , Ameloblastoma/genética , Ameloblastoma/patologia , Ameloblastoma/terapia , Proteínas Proto-Oncogênicas B-raf/genética , Neoplasias Maxilomandibulares/genética , Neoplasias Maxilomandibulares/patologia , Neoplasias Maxilomandibulares/terapia , Resultado do Tratamento , Mutação
4.
Biotech Histochem ; 95(6): 411-417, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32013582

RESUMO

Ameloblastoma is an odontogenic tumor with a slow, locally aggressive growth pattern and multiple clinico-histologic types. The number of stromal myofibroblasts within ameloblastoma often is correlated with growth and aggressiveness. Color-deconvolution to separate different colors of immunostained tissues is a promising approach to quantifying myofibroblasts in tumors such as ameloblastoma. We investigated the reliability of the color-deconvolution method using cross-sectional design to evaluate alpha-smooth muscle actin (α-SMA)-positive myofibroblasts in solid multicystic ameloblastoma. Formalin fixed tissues of eight cases of solid multicystic ameloblastoma were immunostained for α-SMA using the horseradish peroxidase-diaminobenzidine (HRP-DAB) method. Color-deconvolution using ImageJ software was used to quantify the staining intensity of brown DAB α-SMA stained myofibroblasts. Color-deconvoluted images of brown DAB stained tissues exhibited distinct morphological features of solid multicystic ameloblastoma with α-SMA stained myofibroblasts distributed abundantly adjacent to the ameloblastoma epithelial islands. The computed image intensity of α-SMA stained myofibroblasts was quantitatively similar among the different ameloblastoma samples. A combination of color-deconvolution and α-SMA staining of myofibroblasts is a useful diagnostic tool for evaluating histologic differentiation and growth pattern of ameloblastoma.


Assuntos
Actinas/metabolismo , Ameloblastoma/patologia , Músculo Liso/patologia , Miofibroblastos/patologia , Estudos Transversais , Humanos , Reprodutibilidade dos Testes
5.
Arch Oral Biol ; 98: 61-67, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30465934

RESUMO

OBJECTIVES: Ameloblastoma is an aggressive odontogenic jaw neoplasm. Its unlimited growth confers high potential for malignant transformation and recurrence. It is unclear why ameloblastoma is highly recurrent despite surgical resection with a wide margin of normal tissue. While canonical autophagy can be used to degrade and eliminate damaged cellular components, it is also a protective mechanism that provides energy and vital metabolites for cell survival. We used ameloblastoma-derived cells to test the hypothesis that autophagic processes play a role in survival and reactivation of ameloblastoma. METHODS: Primary epithelial (EP-AMCs) and mesenchymal (MS-AMCs) ameloblastoma-derived cells were established from tissue samples of solid multicystic ameloblastoma. Clonogenic capacity and basal autophagic capacity were assessed in ameloblastoma-derived cells relative to human odontoma-derived cells (HODCs) and maxilla-mesenchymal stem cells (MX-MSCs). Ability of ameloblastoma-derived cells to survive and form new ameloblastoma was assessed in mouse tumor xenografts. RESULTS: EP-AMCs were highly clonogenic (p < 0.0001) and demonstrated enhanced basal levels of autophagic proteins microtubule-associated protein 1-light chain 3 (LC3) (p < 0.01), p62 (Sequestosome 1, SQSTM1) (p < 0.01), and the LC3-adapter, melanoregulin (MREG) (p < 0.05) relative to controls. EP-AMCs xenografts regenerated solid ameloblastoma-like tumor with histological features of columnar ameloblast-like cells, loose stellate reticulum-like cells and regions of cystic degeneration characteristic of follicular variant of solid multicystic ameloblastoma. The xenografts also displayed stromal epithelial invaginations strongly reactive to LC3 and p62 suggestive of epithelial-mesenchymal transition and neoplastic odontogenic epithelium. CONCLUSIONS: EP-AMCs exhibit altered autophagic processes that can support survival and recurrence of post-surgical ameloblastoma cells.


Assuntos
Ameloblastoma , Autofagia/fisiologia , Sobrevivência Celular , Tumores Odontogênicos , Proteínas Adaptadoras de Transporte Vesicular , Ameloblastoma/patologia , Ameloblastos/metabolismo , Ameloblastos/patologia , Animais , Proteínas de Transporte/metabolismo , Modelos Animais de Doenças , Transição Epitelial-Mesenquimal , Epitélio/metabolismo , Feminino , Xenoenxertos , Humanos , Peptídeos e Proteínas de Sinalização Intracelular , Células-Tronco Mesenquimais , Camundongos , Proteínas Associadas aos Microtúbulos/metabolismo , Recidiva Local de Neoplasia , Proteína Sequestossoma-1/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
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