Comprehensive insights into the understanding of hypoxia in ameloblastoma

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

Classificatory updates in verrucous and cuniculatum carcinomas: Insights from the 5th edition of WHO-IARC head and neck tumor classification

The International Agency for Research on Cancer (IARC) and World Health Organization (WHO) collaboratively produce the 'WHO Blue Books' essential tools standardizing the diagnostic process for human cancers. Regular updates in this classification accommodate emerging molecular discoveries, advances in immunohistochemical techniques, and evolving clinical insights. The 5th edition of the WHO/IARC classification of head and neck tumors refines the 'Oral Cavity and Mobile Tongue' chapter, including sections for non-neoplastic lesions, epithelial tumors, and tumors of uncertain histogenesis. Notably, the epithelial tumors section is rearranged by tumor behavior, starting with benign squamous papillomas and progressing through potentially malignant oral disorders to oral squamous cell carcinoma (OSCC). The section on OSCC reflects recent information on epidemiology, pathogenesis, and histological prognostic factors. Noteworthy is the specific categorization of verrucous carcinoma (VC) and carcinoma cuniculatum (CC), both associated with the oral cavity and distinct in clinical and histologic characteristics. This classification adjustment emphasizes the oral cavity as their predominant site in the head and neck. Designating specific sections for VC and CC aims to provide comprehensive insights into these unique subtypes, elucidating their clinical features, distinct histological characteristics, prevalence, significance, and clinical relevance. By categorizing these subtypes into specific sections, the 5th edition of the WHO classification aims to provide a more nuanced and detailed account, enhancing our understanding of these specific variants within the broader spectrum of head and neck tumors

Clinicopathological and molecular insights into odontogenic tumors associated with syndromes: a comprehensive review.

The association between genetic syndromes and odontogenic tumors encompasses several entities, reflecting the intricate interplay between genetic factors and the development of these lesions. The present study aimed to comprehensively investigate the associations between genetic syndromes and odontogenic tumors. We delineated the diverse spectrum of syndromic connections, including key syndromes such as Gardner syndrome, Gorlin syndrome, Schimmelpenning syndrome, and others. Our findings underscore the clinical significance of recognizing odontogenic tumors associated with genetic syndromes as diagnostic indicators for early intervention. We advocate for multidisciplinary collaboration among clinicians, geneticists, and researchers to deepen our understanding of the underlying mechanisms driving these syndromic associations. In light of this, our study contributes to the growing body of knowledge in dentistry and medical genetics, offering insights that may inform clinical practice and enhance patient care for individuals affected by genetic syndromes and odontogenic tumors

Granular cells in ghost cell odontogenic lesions: an unusual and unexpected finding

This study aimed to present two cases of ghost cell odontogenic lesions (GCOL) with granular cells, an unusual finding, in order to contribute to their immunohistochemical characterization and compare results with previous reports. One case corresponded to a calcifying odontogenic cyst (COC) in a 44-year-old man and the other to a dentinogenic ghost cell tumor (DGCT) presenting in an 84-year-old woman. Both lesions were located in the mandible. Microscopically, COC showed a cystic wall lined by ameloblastic/ameloblastomatous epithelium with ghost cells, and DGCT showed ameloblastomatous proliferation with ghost cells and dentinoid/osteodentin matrix. In addition, the presence of cells with abundant granular cytoplasm was observed within the epithelial lining in the cystic lesion and trapped in the dentinoid matrix in the neoplastic lesion. In both cases, the granular cells were positive for AE1-AE3, S100, and CD68; additionally, granular cells in the DGCT were positive for CK19, amelogenin, β-catenin, E-cadherin, vimentin, and lysozyme. The immunohistochemical profile suggests an epithelial origin of granular cells with an increase in lysosomes possibly associated with a degenerative process. Further studies are necessary to clarify the origin of these cells

Perfil Imunohistoquímico de Ki-67, 8-Ohdg, Bax E Bcl-2 em Leucoplasia Oral e Carcinoma Espinocelular em pacientes com até 40 anos: dados preliminares de uma análise comparativa

As desordens orais potencialmente malignas (DOPMs) são definidas como alterações na mucosa oral associadas com aumento de risco de desenvolvimento de câncer (WARNAKULASURIYA, 2021). A leucoplasia oral (LO), a mais comum entre as DOPMs, tem prevalência estimada entre 2,60% e 4,11% (MELLO, 2018), com o tabaco e o consumo excessivo de álcool constituindo seus principais fatores de risco. Estima-se que a taxa global de transformação maligna da LO varie entre 1,1% e 40,8%, - o que pode ser atribuído à diversidade de patologias sob esse diagnóstico clínico (AGUIRRE-URIZAR, 2021). A graduação histopatológica da displasia epitelial oral (DEO) representa o principal método para avaliar o risco de transformação maligna em DOPMs. No entanto, a falta de consenso entre os patologistas sobre a avaliação histológica da presença e do grau de displasia é evidente. (ODELL, 2021)

Does smoking habit affect dendritic cell expression in oral squamous cell carcinoma?

The aim of this study was to determine the presence of immature CD1a+ and mature CD83+ dendritic cells in oral squamous cell carcinoma, to compare immunoreactivity between smokers and nonsmokers, and to correlate the results with histopathological grading. In this observational study, twenty-eight paraffin-embedded biopsies of oral squamous cell carcinoma were retrospectively retrieved and submitted to immunohistochemistry for immature CD1a+ and mature CD83+. Descriptive and statistical analyses were performed. The sample consisted of 18 man (64.3%) and 10 women (35.7%), with a mean age of 64.6 years in the nonsmoker group and 53.2 years in the smoker group. The tongue (11 cases, 39.2%) was the most commonly affected anatomical site, followed by gingiva (6 cases, 21.4%). Histopathological grading revealed 7 low-grade and 7 high-grade malignancy cases in each group, and no correlation with the number of positive DCs. The number of immature CD1a+ was not significantly different between smoker and nonsmoker groups, while a lower number of mature CD83+ was detected in the smoker group (p = 0.001). Smoking changes the oral immune system and decreases the ability to activate and mature dendritic cells, which may influence the development and progression of oral squamous cell carcinoma.CNPq - Conselho Nacional de Desenvolvimento Científico e TecnológicoCAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superio

Frequency of BRAF V600E immunoexpression in ameloblastomas: a multi-institutional analysis of 86 cases in Latin America and comprehensive review of the literature

Artículo disponible a texto completo a través de PubMed Central. Artículo head of print- article in press.Background: The initiation of odontogenic tumorigenesis often involves the activation of the MAP-kinase path- way, with a pivotal role played by the BRAF V600E mutation. This study aimed to investigate the frequency of BRAF V600E immunoexpresion in ameloblastomas diagnosed in four Latin American centers and correlate this finding with the histological types and subtypes of the analyzed cases.Material and Methods: A total of 86 samples of ameloblastomas were examined for immunohistochemistry using anti-BRAF V600E antibody. The histopathological features of each case were analyzed. Results: Positivity for anti-BRAF V600E antibody was detected in 65/86 cases (75.6%). BRAF V600E was positive in 38/56 cases (67.9%) of conventional ameloblastomas and in 27/30 cases (90.0%) of unicystic ameloblastomas. A statistically significant difference in BRAF V600E positivity was observed when comparing unicystic ameloblastomas to conventional ameloblastomas (p=0.03). No statistically significant difference in BRAF V600E positivity was observed when comparing histological variants, both for conventional ameloblastomas and unicystic ameloblastomas. Conclusions: This study highlights a high frequency of BRAF V600E immunoreactivity in ameloblastomas among Latin American cases. The prevalence of the BRAF V600E immunoexpresion may suggest the feasibility of utilizing BRAF-targeted therapy for ameloblastomas with this mutation.Comisión Sectorial de Investigación Científica - Uruguay; Agencia Nacional de Investigación e Innovación / Sistema Nacional de Investigadores - Uruguay

DNA damage-related proteins in smokers and non-smokers with oral cancer

Tobacco smoking involves a high risk of human malignancies, including oral cancer, because it contains multiple carcinogens that cause genetic instability. Thus, a worse prognosis would be expected for cancer patients who are smokers. The aim of this study was to assess the DNA damage response through the expression of checkpoint kinase 2 (CHK2), H2A histone family member X (H2AX), and P53 among smokers and non-smokers with oral squamous cell carcinoma (OSCC). Associations between immunoexpression of proteins and clinicopathological data and histopathological grading were also analyzed. A total of 35 individuals (18 non-smokers and 17 smokers) with OSCC of the tongue and/or floor of the mouth were included. Immunohistochemistry for H2AX was conducted for the identification of double-strand breaks, CHK2, and P53 to evaluate the expression of this protein in cell cycle regulation. The sample consisted of 22 males and 13 females, with a mean age of 63.9±11.8 years. OSCC of non-smokers were well-differentiated tumors in 50% of the cases, and those of smokers were equally distributed into moderately differentiated and poorly differentiated tumors (35.3% each). Overall, 31 (88.6%) cases were CHK2-positive, 27 (77.1%) were H2AX-positive, and 23 (65.7%) were P53-positive, with no difference between smokers and non-smokers (p > 0.05). No association was found between proteins and clinicopathologic data (p > 0.05). Similarities in CHK2, H2AX, and P53 immunohistochemical staining patterns were observed between smokers and non-smokers, and immunoexpression was not associated with clinicopathological parameters. However, the findings indicated consistent expression of these proteins in OSCC.CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superio

O uso da ubiquinona no reparo dos ossos maxilares: uma revisão sistemática

O presente trabalho apresentou evidências que apoiam o uso de Q10 no reparo dos ossos maxilares e tecidos moles adjacentes. No entanto, a literatura ainda não apresenta ensaios clínicos que investiguem seu efeito nesses tecidos. Novos e bem delineados estudos são fundamentais a fim de fornecer evidências suficientes para apoiar futuras aplicações da Q10 na clínica odontológica

Hypoxia-inducible factor-1α at the invasive tumor front in oral squamous cell carcinoma.

BACKGROUND Hypoxia in oral cancer promotes tumoral invasion by inducing epithelial-mesenchymal transition, leading to aggressive tumor progression. AIM To characterize the expression of hypoxia-inducible factor 1-alpha (HIF-1α) at the invasive tumor front (ITF) in comparison to tumor islands (TI) in oral squamous cell carcinoma (OSCC) and to explore its relationship with E-cadherin and Vimentin expression. METHODS Thirty-eight cases of OSCC and five cases of normal oral mucosa (NOM) were included in this study. The ITF was identified based on the region and immune expression of AE1/AE3. Immunohistochemistry was performed to assess the expression of HIF-1α, Vimentin, and E-cadherin. The immunostaining was analyzed using an immunoreactive score, and the results were illustrated using immunofluorescence. RESULTS HIF-1α expression was significantly higher in the TI region compared to the ITF region (P = 0.0134). Additionally, a significant difference was observed between TI and NOM (P = 0.0115). In the ITF regions, HIF-1α expression showed a significant correlation with Vimentin expression, with higher levels of HIF-1α associated with increased Vimentin expression (P = 0.017). CONCLUSION Based on the results of this study, HIF-1α appears to play a distinct role in OSCC tumor progression, underscoring the importance of exploring hypoxia-driven changes in cellular phenotype at the ITF of OSCC. Further research is needed to better understand their impact on OSCC prognosis.Comisión Sectorial de Investigación Científica (CSIC - Grupo de investigación 88180); Agencia Nacional de Investigación e Innovación/Sistema Nacional de Investigadores (ANII/SNI); Programa de Desarrollo de las Ciencias Básicas (PEDECIBA), Uruguay