Immunohistochemical analysis of SHH, SMO and GLI-1 proteins in epithelial odontogenic lesions.

The present study analyzed the expression of proteins involved in the sonic hedgehog signaling pathway (SHH, SMO, and GLI-1) in benign epithelial odontogenic lesions (odontogenic keratocyst - OKC, ameloblastoma - AB, and adenomatoid odontogenic tumor - AOT) in order to identify the role of these proteins in the pathogenesis of these lesions. The sample consisted of 20 OKCs, 20 ABs, and 10 AOTs. The Kruskal-Wallis, Mann-Whitney U, and Spearman's (r) tests were used for statistical analysis, with the level of significance set at 5% (p < 0.05). The membrane/cytoplasmic expression of SHH was significantly higher in AB compared to AOT (p = 0.022) and OKC (p = 0.02). No differences were found in the membrane/cytoplasmic expression of SMO between the lesions studied. Regarding GLI-1, significant differences were observed at the nuclear level for AB and OKC compared to AOT (p < 0.0001). In addition, significant positive correlations were found between cytoplasmic and nuclear GLI-1 in AB (r = 0.482; p = 0.031) and OKC (r = 0.865; p < 0.0001), and between membrane/cytoplasmic SMO and cytoplasmic GLI-1 in AOT (r = 0.667; p = 0.035) and OKC (r = 0.535; p = 0.015). The results of this study confirm the participation of the sonic hedgehog signaling pathway in the pathogenesis of the lesions studied. Overexpression of SHH in ABs and nuclear expression of GLI-1 in ABs and OKCs indicate that these proteins contribute to the more aggressive behavior of these two lesions when compared to AOT.

Immunohistochemical analysis of SHH, SMO and GLI-1 proteins in epithelial odontogenic lesions

Abstract The present study analyzed the expression of proteins involved in the sonic hedgehog signaling pathway (SHH, SMO, and GLI-1) in benign epithelial odontogenic lesions (odontogenic keratocyst - OKC, ameloblastoma - AB, and adenomatoid odontogenic tumor - AOT) in order to identify the role of these proteins in the pathogenesis of these lesions. The sample consisted of 20 OKCs, 20 ABs, and 10 AOTs. The Kruskal-Wallis, Mann-Whitney U, and Spearman's (r) tests were used for statistical analysis, with the level of significance set at 5% (p < 0.05). The membrane/cytoplasmic expression of SHH was significantly higher in AB compared to AOT (p = 0.022) and OKC (p = 0.02). No differences were found in the membrane/cytoplasmic expression of SMO between the lesions studied. Regarding GLI-1, significant differences were observed at the nuclear level for AB and OKC compared to AOT (p < 0.0001). In addition, significant positive correlations were found between cytoplasmic and nuclear GLI-1 in AB (r = 0.482; p = 0.031) and OKC (r = 0.865; p < 0.0001), and between membrane/cytoplasmic SMO and cytoplasmic GLI-1 in AOT (r = 0.667; p = 0.035) and OKC (r = 0.535; p = 0.015). The results of this study confirm the participation of the sonic hedgehog signaling pathway in the pathogenesis of the lesions studied. Overexpression of SHH in ABs and nuclear expression of GLI-1 in ABs and OKCs indicate that these proteins contribute to the more aggressive behavior of these two lesions when compared to AOT.

Resumo O presente estudo analisou a expressão de proteínas envolvidas na via de sinalização Sonic Hedgehog (SHH, SMO e GLI-1) em lesões benignas do epitélio odontogênico de comportamento biológico distintos, tais como ceratocistos odontogênicos (CO), ameloblastomas (AMB) e tumores odontogênicos adenomatoides (TOA), com o intuito de identificar o papel destas proteínas na patogênese destas lesões. A amostra foi constituída de 20 CO, 20 AMB e 10 TOA, analisada pela técnica da imuno-histoquímica de forma semiquantitativa por compartimento celular, onde foi feita uma análise da membrana e citoplasma das células nas proteínas SHH e SMO, enquanto que para a proteína GLI-1, foi feita uma análise nuclear e/ou citoplasmática. Para análise estatística, foram utilizados os testes de Kruskal-Wallis (KW), Mann-Whitney (U) e Spearman (r), com o nível de significância estabelecido em 5% (p < 0,05). Ao analisar a proteína SHH, observou-se que o AMB demonstrou expressão membranar/citoplasmática significativamente maior em comparação ao TOA (p = 0,022) e CO (p = 0,020). Com relação à análise membranar/citoplasmática da SMO, não foram identificadas diferenças entre as lesões estudadas. Para a proteína GLI-1, foram constatadas diferenças estatisticamente significativas, em nível nuclear, para o AMB e CO em comparação ao TOA (p< 0,0001). Além disso, foram observadas correlações positivas com significância estatística entre GLI-1 citoplasmático e GLI-1 nuclear para o AMB (r = 0,482; p = 0,031) e CO (r = 0,865; p< 0,0001), e entre o SMO membranar/citoplasmático e o GLI-1 citoplasmático para o TOA (r = 0,667; p = 0,035) e o CO (r = 0,535; p = 0,015). Os resultados deste estudo confirmam a participação da via de sinalização Sonic Hedgehog na patogênese das lesões estudadas e, a superexpressão de SHH em AMBs e GLI-1 nuclear em AMBs e COs, indica que estas proteínas contribuem com o comportamento biológico mais agressivo destas duas lesões quando comparado ao TOA.

Oral Alterations in a COVID-19 Patient: Case Report and Update of Main Findings

ABSTRACT: COVID-19 was characterized as a pandemic due to the worldwide dissemination and the severity with which the disease attacks the human organism. Some oral lesions have been observed in COVID-19 patients. However, there is still no concrete evidence of the real influence of SARS-CoV-2 on the human body, especially in the oral region. In this context, the present report discusses a case of a COVID-19 patient with oral alterations. The male patient presented ulcerative lesions of painful symptomatology and petechiae in the oral mucosa. This study also performed a literature review of the main oral alterations reported in the literature. Although more studies with a larger number of cases should be performe d, the present clinical case may have manifested signs of this pathology in the oral cavity since the epithelial cells of the oral mucosa have ACE2 receptors.

RESUMEN: El COVID-19 se caracterizó como una pandemia debido a la diseminación mundial y la gravedad con la que la enfermedad ataca al organismo humano. Se han observado algunas lesiones orales en pacientes con COVID-19. Sin embargo, todavía no hay evidencia concreta de la influencia del SARS-CoV-2 en el cuerpo humano, especialmente en la cavidad oral. En este contexto, el presente reporte analiza un caso de un paciente con COVID-19 con alteraciones orales. El paciente de sexo masculino presentó lesiones ulcerativas de sintomatología dolorosa y petequias en la mucosa oral. Este estudio también realizó una revisión de la literatura de las principales alteraciones orales reportadas en la literatura. Si bien se deben realizar más estudios con un mayor número de pacientes, el presente reporte de caso puede haber manifestado signos de esta patología en la cavidad oral ya que las células epiteliales de la mucosa oral tienen receptores ACE2.

Manifestações clínicas e opções terapêuticas do líquen plano oral: uma revisão de literatura / Clinical manifestations and therapeutic options of oral lichen planus: a literature review

O Líquen plano oral (LPO) é uma doença inflamatória crônica, caracterizada por uma resposta imune com agressão ao epitélio de revestimento, principalmente na camada basal. Por tratar-se de uma doença de etiopatogenia complexa, o LPO é comumente tratado com agentes anti-inflamatórios e corticosteroides tópicos, que buscam atenuar sinais e sintomas. Diante do exposto, este trabalho objetivou realizar uma revisão de literatura sobre o LPO, suas manifestações clínicas e opções terapêuticas. Foi realizada a busca eletrônica de publicações nas bases de dados Google Scholar, Pubmed e SciELO, utilizando os seguintes descritores: "líquen plano", "cavidade oral" e "estomatologia", e o operador booleano "AND". Em seguida, foi realizada análise a partir da leitura criteriosa dos artigos, realizou-se então a seleção de 60 trabalhos. Após o emprego dos critérios de elegibilidade, 29 artigos foram selecionados para o presente estudo. Os estudos demonstraram que o LPO possui etiologia indeterminada, tornando importante um amplo conhecimento de suas manifestações clínicas para melhor diagnóstico. Além dos corticosteroides, novas modalidades terapêuticas têm sido sugeridas e trazido bons resultados, como a laserterapia de baixa potência. Ademais, é importante para o cirurgião-dentista reconhecer suas diversas opções terapêuticas a fim de diminuir o agravo das lesões orais, visto que, a depender do quadro imunológico do paciente, poderão ocorrer remissões espontâneas... (AU)

Oral lichen planus (OLP) is a chronic inflammatory disease, characterized by an immune response with aggression to the lining epithelium, mainly in the basal layer. Since it is a disease of complex eti opathogenesis, OLP is commonly treated with anti-inflammatory agents and topical corticosteroids, which seek to decrease signs and symptoms. Thus, this study performed a literature review abour OLP, its clinical manifestations and therapeutic options. The electronic search for publications in the Google Scholar, Pubmed and SciELO databases was performed, using the following descriptors: "li chen planus", "oral cavity" and "stomatology", and the Boolean operator "AND". Then, an analysis was performed based on the careful reading of the articles, and then 60 articles were selected. After using the eligibility criteria, 29 articles were selected for the present study. Studies have shown that OLP has an undetermined etiology, making it important to have a broad knowledge of its clinical manifestations for a better diagnosis. In addition to corticosteroids, new therapeutic modalities have been suggested and brought good results, such as low-level laser therapy. In addition, it is important for the dentists to recognize their various therapeutic options to reduce the worsening of oral lesions, since, depending on the patient's immune status, spontaneous remissions may occur... (AU)

Saliva, implicações orais e biossegurança em Odontologia: principais aspectos do COVID-19 / Saliva, oral implications and biosafety in Dentistry: main aspects in COVID-19

Objetivo: Diante da importância do fluido salivar no contexto da odontologia, este trabalho objetivou realizar uma revisão de literatura sobre a relação da saliva e a COVID-19, bem como as suas principais implicações na Odontologia. Métodos: Foi realizada a busca eletrônica de publicações nas bases de dados SciELO, PubMed, Scopus, EMBASE e Cochrane Central Register of Controlled Trials, utilizando os seguintes descritores: "Saliva", "oral cavity", "oral mucosa", "oral lesions", "Dentistry", e o operador booleano "AND" entre todas as palavras-chave citadas individualmente com o termo "COVID-19". Os estudos foram publicados no período de dezembro de 2019 a setembro de 2020. Resultados: Os estudos demonstraram que a saliva representa um importante meio de transmissão do SARS-CoV-2, o que torna necessário o cumprimento de medidas de biossegurança pelos cirurgiões-dentistas a fim de reduzir a possibilidade de infecção pelo SARS-CoV-2. Ao mesmo tempo, a alta carga viral encontrada na saliva possibilita que a mesma possa ser utilizada como um meio para diagnóstico da COVID-19. Pesquisas têm demonstrado eficácia similar da análise da saliva quando comparada a outras técnicas convencionais. Por sua vez, mais investigações precisam ser realizadas a fim de validar a metodologia aplicada nos estudos atuais. Conclusão: A detecção do SARS-CoV-2 através da saliva é bastante promissora e apresenta vantagens em comparação a outros fluidos biológicos, pois a coleta deste fluido não envolve uma intervenção invasiva, facilitando o manejo pelos profissionais e pacientes.

Aim: Due to the importance of the salivary fluid in dentistry, this study aimed to carry out a literature review on the relationship between saliva and COVID-19, as well as its main implications in Dentistry. Methods: An electronic search for publications was performed in the SciELO, PubMed, Scopus, EMBASE, and Cochrane Central Register of Controlled Trials databases using the following descriptors: "Saliva", "oral cavity", "oral mucosa", "oral lesions ", and "Dentistry", using the Boolean operator "AND" between all keywords cited individually with the term "COVID-19". The studies were published from December 2019 to September 2020.Results: The studies have shown that saliva represents an important means of transmission of SARS-CoV-2, which makes it necessary for dentists to comply with biosafety measures in order to reduce the possibility of SARS-CoV-2 infection. Likewise, the high viral load found in saliva allows it to be used as a path to COVID-19 diagnosis. Investigations have shown similar effectiveness in the saliva analysis compared to other conventional techniques. In this regard, more investigations need to be carried out to validate the methodology applied in current studies. Conclusion: The detection of SARS-CoV-2 through saliva is very promising and has advantages in comparison to other biological fluids, as the collection of this fluid does not involve an invasive intervention, thus facilitating management by professionals and patients.

Role of Twist and Podoplanin in Partial Epithelial-Mesenchymal Transition in Oral Squamous Cell Carcinoma.

The aim of this study was to perform a comparative analysis of podoplanin (PDPN) and Twist immunoexpressions in lower lip and oral tongue squamous cell carcinomas (LLSCC and OTSCC, respectively). PDPN and Twist immunoexpressions were semi-quantitatively evaluated by analyzing the invasion front, the compressive areas, the large islands and nests and dissociated cells of the chosen carcinomas. Their statistical associations and correlations with clinical-pathological characteristics were verified by the Mann-Whitney and Spearman's test. Twist expression was low in both carcinomas, with <25% labeling on the invasive front. Significant differences were observed for LLSCC (p=0.032) and OTSCC (p=0.025) regarding PDPN immunoexpression in relation to the worst invasion patterns determined by a histological malignancy gradation system. Statistically significant negative correlations between PDPN membrane expression and general (r=-0.356, p=0.024) and cytoplasmic Twist expressions (r=-0.336; p=0.034) in LLSCC were also observed. Twist and PDPN are suggested to be associated to a more aggressive invasion pattern in both LLSCC and OTSCC cases but not related to the different biological behaviors on these anatomical sites. Also, it was seen that PDPN membrane expression is inversely related to general and cytoplasmic Twist expression in LLSCC cases.

Role of twist and podoplanin in partial epithelial-mesenchymal transition in oral squamous cell carcinoma

Abstract The aim of this study was to perform a comparative analysis of podoplanin (PDPN) and Twist immunoexpressions in lower lip and oral tongue squamous cell carcinomas (LLSCC and OTSCC, respectively). PDPN and Twist immunoexpressions were semi-quantitatively evaluated by analyzing the invasion front, the compressive areas, the large islands and nests and dissociated cells of the chosen carcinomas. Their statistical associations and correlations with clinical-pathological characteristics were verified by the Mann-Whitney and Spearman's test. Twist expression was low in both carcinomas, with <25% labeling on the invasive front. Significant differences were observed for LLSCC (p=0.032) and OTSCC (p=0.025) regarding PDPN immunoexpression in relation to the worst invasion patterns determined by a histological malignancy gradation system. Statistically significant negative correlations between PDPN membrane expression and general (r=-0.356, p=0.024) and cytoplasmic Twist expressions (r=-0.336; p=0.034) in LLSCC were also observed. Twist and PDPN are suggested to be associated to a more aggressive invasion pattern in both LLSCC and OTSCC cases but not related to the different biological behaviors on these anatomical sites. Also, it was seen that PDPN membrane expression is inversely related to general and cytoplasmic Twist expression in LLSCC cases.

Resumo O objetivo deste estudo foi realizar uma análise comparativa das imunoexpressões de podoplanina (PDPN) e Twist em carcinomas de células escamosas de lábio inferior e língua oral (CCELI e CCELO, respectivamente). As imunoexpressões de PDPN e Twist foram avaliadas semi-quantitativamente através da análise do front invasivo, das áreas compressivas, das grandes ilhas e ninhos e das células dissociadas dos carcinomas escolhidos. Suas associações estatísticas e correlações com características clínico-patológicas foram verificadas pelos testes de Mann-Whitney e Spearman. A expressão de Twist foi baixa nos dois carcinomas, com marcação <25% no front invasivo. Diferenças significativas foram observadas para CCELI (p=0,032) e CCELO (p=0,025) em relação à imunoexpressão de PDPN em relação aos piores padrões de invasão determinados por um sistema de gradação histológica de malignidade. Também foram observadas correlações negativas estatisticamente significantes entre a expressão membranar de PDPN e as expressões geral (r=-0,356, p=0,024) e citoplasmática do Twist (r=-0,336; p=0,034) no CCELI. Sugere-se que o Twist e o PDPN estejam associados a um padrão de invasão mais agressivo nos casos de CCELI e CCELO, mas não relacionados aos diferentes comportamentos biológicos nesses sítios anatômicos. Também foi observado que a expressão membranar de PDPN está inversamente relacionada à expressão geral e citoplasmática de Twist em casos de CCELI.

Immunohistochemical expression of DNA repair proteins in oral tongue and lower lip squamous cell carcinoma.

The DNA repair system involves genes and proteins that are essential for the maintenance of genome integrity and the consequent control of various cellular processes. Alterations in these genes and proteins play a role in tumor development and progression and might be associated with prognosis. The aims of this study were to analyze the immunoexpression of two DNA repair proteins, XPF and XRCC1, in lower lip squamous cell carcinoma (LLSCC) and oral tongue squamous cell carcinoma (OTSCC), and to investigate possible associations with clinical and histopathological parameters. The immunohistochemical expression of XPF and XRCC1 was analyzed semi-quantitatively in 40 cases each of LLSCC and OTSCC. The chi-squared test or Fisher's exact test, when appropriate, was used to investigate the association between expression of the proteins and clinicopathological characteristics. The cytoplasmic immunoexpression of XPF was high in OTSCC (95% of the cases analyzed) but low in LLSCC (52.5%). Among the clinicopathological parameters evaluated, a statistically significant association was observed between high nuclear expression of XRCC1 and the absence of regional lymph node metastasis in patients diagnosed with OTSCC (p=0.006). The high protein expression of XPF and XRCC1 in OTSCC and LLSCC suggests an important role in the development and progression of these tumors. Our study found an association between high nuclear expression of XRCC1 and the absence of loco-regional metastasis in cases diagnosed as OTSCC, suggesting a role of this protein in tumor progression.

Dermoid and epidermoid cysts of the oral cavity: a 48-year retrospective study with focus on clinical and morphological features and review of main topics

BACKGROUND: Dermoid and epidermoid cysts are slow-growing, benign developmental cysts that arise from ecto-dermal tissue and can occur anywhere in the body. Less than 7% of these cysts involve the head and neck region, with only 1.6% of cases presenting in the oral cavity. To evaluate the clinical and histopathological features of dermoid (DCs) and epidermoid (ECs) cysts stored in the archives of a referred Oral Pathology Service over a 48-year-period, and to review current concepts about these cysts. MATERIAL AND METHODS: All DCs and ECs were reviewed, and clinical data were obtained from the patient records. Fourteen cases of DCs and thirteen cases of ECs were re-evaluated microscopically by 2 oral pathologists. RESULTS: Among 15.387 cases, 14 (0.09%) had a histopathological diagnosis of DCs and 13 (0.08%) of ECs. For DCs, ten (71.4%) patients were women, with the mean age of 37.2 years. All DCs were lined by a stratified squamous epithelium (100%), with gut and respiratory epithelium observed in 1 (7.1%) and 2 (14.3%) cases, respectively. Chronic inflammatory cells, melanin, multinucleated giant cell reaction, and Pacini bodies were also observed. For ECs, eight (61.5%) cases were in women, and the mean age was 38.2 years. All ECs were lined by a stratified squamous epithelium (100%). Chronic inflammatory cells, melanin pigmentation, and adipose tissue were observed in the fibrous capsule. CONCLUSION: Our results suggest that stratified squamous epithelium is the predominant epithelial lining of these cystic lesions. Also, we may find some unusual findings in DCs, such as Pacini bodies

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Immunoexpression of DNA base excision repair and nucleotide excision repair proteins in ameloblastomas, syndromic and non-syndromic odontogenic keratocysts and dentigerous cysts.

OBJECTIVE: To evaluate the immunoexpression of DNA base excision repair (BER) [apurinic/apyrimidinic endonuclease 1 (APE-1), X-ray repair cross complementing 1 (XRCC-1)] and nucleotide excision repair (NER) [xeroderma pigmentosum complementation group (XPF)] proteins in benign epithelial odontogenic lesions with different biological behaviors. DESIGN: Thirty solid ameloblastomas, 30 non-syndromic odontogenic keratocysts (NSOKCs), 29 syndromic odontogenic keratocysts (SKOCs), 30 dentigerous cysts (DCs) and 20 dental follicles (DFs) were evaluated quantitatively for APE-1, XRCC-1 and XPF through immunohistochemistry. RESULTS: Nuclear expression of APE-1 was significantly higher in NSOKCs, SOKCs, and ameloblastomas in comparison to DCs (p < 0.001). Nuclear expression of XRCC-1 was higher in NSOKCs and SOKCs than in DCs (p < 0.05). At the nuclear level, XPF expression was higher in NSOKCs and SOKCs than in DCs and ameloblastomas (p < 0.05). A statistically significant higher expression of APE-1 (nuclear), XRCC-1 (nuclear), and XPF (nuclear and cytoplasmic) was found in all odontogenic lesion samples as compared to DFs (p < 0.05). For all lesions, there was a positive correlation between nuclear expression of APE-1 and XRCC-1 or XPF (p < 0.05). CONCLUSIONS: Our results suggest a potential involvement of APE-1, XRCC-1 and XPF proteins in the pathogenesis of benign epithelial odontogenic lesions, especially in those with more aggressive biological behavior, such as ameloblastomas, NSOKCs, and SOKCs. We also showed that the expression of APE-1 was positively correlated with the nuclear expression of XRCC-1 and XPF, which may suggest an interaction between the BER and NER pathways in all odontogenic lesions studied herein.

Immunohistochemical expression of DNA repair proteins in oral tongue and lower lip squamous cell carcinoma

Abstract The DNA repair system involves genes and proteins that are essential for the maintenance of genome integrity and the consequent control of various cellular processes. Alterations in these genes and proteins play a role in tumor development and progression and might be associated with prognosis. The aims of this study were to analyze the immunoexpression of two DNA repair proteins, XPF and XRCC1, in lower lip squamous cell carcinoma (LLSCC) and oral tongue squamous cell carcinoma (OTSCC), and to investigate possible associations with clinical and histopathological parameters. The immunohistochemical expression of XPF and XRCC1 was analyzed semi-quantitatively in 40 cases each of LLSCC and OTSCC. The chi-squared test or Fisher's exact test, when appropriate, was used to investigate the association between expression of the proteins and clinicopathological characteristics. The cytoplasmic immunoexpression of XPF was high in OTSCC (95% of the cases analyzed) but low in LLSCC (52.5%). Among the clinicopathological parameters evaluated, a statistically significant association was observed between high nuclear expression of XRCC1 and the absence of regional lymph node metastasis in patients diagnosed with OTSCC (p=0.006). The high protein expression of XPF and XRCC1 in OTSCC and LLSCC suggests an important role in the development and progression of these tumors. Our study found an association between high nuclear expression of XRCC1 and the absence of loco-regional metastasis in cases diagnosed as OTSCC, suggesting a role of this protein in tumor progression.

Immunoexpression of human leukocyte antigen-DR in actinic cheilitis and lower lip squamous cell carcinoma.

The aim of this study was to evaluate the immunoexpression of human leukocyte antigen-DR (HLA-DR) in actinic cheilitis (AC) and lower lip squamous cell carcinoma (LLSCC), and to correlate the findings with clinical (tumor size/extent, regional lymph node metastasis, and clinical stage) and histopathological (grade of epithelial dysplasia and inflammatory infiltrate for AC and histopathological grade of malignancy for LLSCC) parameters. Twenty-four AC and 48 LLSCC cases (24 with regional nodal metastasis and 24 without regional nodal metastasis) were selected. The scores of immunopositive cells for HLA-DR in the epithelial component of the lesions were assessed and the results were analyzed statistically using the nonparametric Mann-Whitney test. Epithelial expression of HLA-DR was observed in only five (20.8%) cases of AC (two low-grade and three high-grade lesions), with a very low median score of immunopositivity. By contrast, expression of HLA-DR was found in most LLSCC (97.9%), with a relatively high median score of positive cells. The score of HLA-DR-positive cells tended to be higher in tumors with regional lymph node metastasis, tumors in advanced clinical stages, and low-grade tumors, but the difference was not statistically significant (p > 0.05). In addition, there was a tendency towards higher expression of HLA-DR in highly/moderately keratinized tumors, and tumors with little/moderate nuclear pleomorphism (p > 0.05). The results suggest a potential role of HLA-DR in lip carcinogenesis, particularly in the development and progression of LLSCC. The expression of this protein can be related to the degree of cell differentiation in these tumors.

Association of polymorphisms in IL-8, MMP-1 and MMP-13 with the risk and prognosis of oral and oropharyngeal squamous cell carcinoma.

OBJECTIVE: This study investigated the risk and prognostic value of single nucleotide polymorphisms (SNP) inIL-8, MMP-1 and MMP-13 in oral and oropharyngeal squamous cell carcinomas (SCCs). DESIGN: SNPs rs2227532 and rs4073 inIL-8, rs2071230 and rs470558 in MMP-1, and rs2252070 in MMP-13 were genotyped in 125 oral and oropharyngeal SCC patients and 130 healthy controls, using TaqMan allelic discrimination assays. Multiple logistic regression models were used to explore the association between SNPs and cancer development, as well as SNP-SNP interaction and gene-environmental factor (GxE) interaction. Univariate and multivariate methods were applied for survival analyses. RESULTS: With exception of rs2227532, all the SNPs were in Hardy-Weinberg equilibrium in the control. No associations between rs4073 in IL-8 and rs2071230 and rs470558 in MMP-1 were observed, but rs2252070 in MMP-13, in the dominant model, was associated in a protective manner to oral and oropharyngeal SCC (OR: 0.20, 95% CI: 0.06-0.71, p = 0.007). All SNPs interact significantly with cigarette smoking and alcohol consumption on susceptibility to oral and oropharyngeal SCC, but they showed no influence on survival of the patients. CONCLUSIONS: Our results show that rs2252070 inMMP-13 may confer protection effect against oral and oropharyngeal SCC. In addition, the combined effects of IL-8 (rs4073), MMP-1 (rs2071230 and rs470558) and MMP-13 (rs2252070) with environmental carcinogens, such as tobacco and alcohol, are related to increased risk for oral and oropharyngeal SCC development.

Oral lichen sclerosus: a rare case and update.

Lichen sclerosus (LS) is a chronic inflammatory mucocutaneous disease that often affects the anogenital area; oral mucosal lesions are extremely rare. A 52-year-old woman presented for evaluation of an 8-year history of a persistent whitish plaque in the buccal mucosa. Intraoral examination revealed multiple elevated whitish plaques diffusely distributed in the buccal mucosa associated with an area of tissue atrophy. Although both leukoplakia and lichen planus were considered, incisional biopsy and later, full excision confirmed the histopathological diagnosis of oral LS. After 6 months of follow-up, there are no clinical signs of relapse. This case highlights the importance of clinical and histopathological findings for the correct diagnosis and treatment of oral LS.

Immunohistochemical evaluation of HLA-G and FoxP3+ T regulatory cells in oral cavity and lower lip squamous cell carcinomas.

Human Leukocyte Antigen G (HLA-G) is a molecule involved in the tumor immunosuppression and also in the generation of regulatory T (Treg) cells, thus leading to evasion to the immune system host, and consequently, contributing to tumor progression in several cancers. The aim of this study was to evaluate the immunoexpression of HLA-G by tumor cells and FoxP3+ Treg cells in 25 oral tongue squamous cell carcinomas (SCCs) and 25 lower lip SCCs and analyze their relationship with clinical parameters. HLA-G expression was higher in oral tongue SCCs than in lower lip SCCs. In oral tongue SCCs and lower lip SCCs, no association between HLA-G expression and clinical parameters (tumor size, lymph node status, distant metastasis, and clinical stage) was verified (P>0.05). FoxP3+ Treg cells were detected along the tumor invasive front in all cases of oral tongue and lower lip SCCs. In oral tongue SCC cases, the number of Treg cells tended to be higher in smaller tumors, tumors without regional lymph node metastasis, and tumors in early clinical stages, but the difference was not statistically significant (P>0.05). A significant positive correlation was found between the expression of HLA-G by neoplastic cells and Treg cells in lower lip SCCs (p = 0.008). Our findings suggest the involvement of HLA-G and Treg cells in the modulation of immune responses in oral tongue and lower lip SCCs. This interaction between HLA-G and Treg cells may represent an evasion mechanism in these malignancies.

Regulation of Wnt/ß-catenin pathway may be related to Regγ in benign epithelial odontogenic lesions.

OBJECTIVES: The aim of this study was to analyze and compare the immunoexpressions of Regγ, Wnt-1, and ß-catenin in ameloblastomas, adenomatoid odontogenic tumors (AOTs), and odontogenic keratocysts (OKCs). STUDY DESIGN: Thirty solid ameloblastomas, 20 AOTs, and 30 OKCs were selected for analysis of the immunoexpression of Regγ, Wnt-1, and ß-catenin. Each case was semiquantitatively evaluated in the epithelial component and in their different cellular compartments (membrane, cytoplasm, and nucleus). RESULTS: Ameloblastomas displayed higher cytoplasmic and nuclear Regγ expression compared with AOTs and OKCs, as well as higher membrane and cytoplasmic Wnt-1 expression (P < .05). ß-catenin membrane expression was higher in OKCs compared with ameloblastomas and AOTs (P < .05). Nuclear ß-catenin expression was higher in ameloblastomas and AOTs than in OKCs (P < .05). Cytoplasmic and nuclear Regγ expression in AOTs were positively correlated with nuclear ß-catenin expression (P < .05). CONCLUSIONS: The marked expressions of Regγ, Wnt-1, and ß-catenin suggest the participation of these proteins in the pathogenesis of the studied lesions. The greater expressions of Regγ, Wnt-1, and nuclear ß-catenin in ameloblastomas may be related to their more aggressive behavior. Pro-tumor effects of nuclear ß-catenin may be counterbalanced by inhibitory pathways in AOTs, justifying their low aggressiveness.

Clinicopathological and immunohistochemical analysis of spindle cell squamous cell carcinoma of the tongue: a rare case.

Spindle cell squamous cell carcinoma of the tongue is a rare variant of squamous cell carcinoma. This paper reports the case of a spindle cell squamous cell carcinoma of the tongue, in a 64-year-old male patient, and presents a review of the etiopathogenesis, clinicopathological and immunohistochemical features and treatment of the malignancy. The patient presented for evaluation of a painful swelling on his tongue. Extraoral examination revealed palpable submandibular and superior cervical lymph nodes. Based on the presumptive diagnoses of squamous cell carcinoma or malignant salivary gland neoplasm, an incisional biopsy was performed. Histopathological analysis showed a proliferation of atypical spindle cells, exhibiting extensive pleomorphism. Tumor cells were positive for vimentin, P53 and alpha-smooth muscle actin, focally positive for epithelial membrane antigen and P63, and negative for pan-cytokeratin (AE1/AE3), CK7, CD138, CD34, CD56, and S-100. The positivity index for Ki-67 was approximately 40%. The diagnosis of spindle cell squamous cell carcinoma was established and the patient was referred to a head and neck surgery service. In the oral cavity, spindle cell squamous cell carcinoma of the tongue is an aggressive variant of squamous cell carcinoma, which usually presents as an exophytic mass located on the tongue of elderly males. Due to its distinct histopathological characteristics, immunohistochemistry is a valuable and helpful tool to establish the diagnosis of spindle cell squamous cell carcinoma of the tongue.

Self-Medication for Toothache and its Associated Factors in Children and Adolescents

Objective: To evaluate self-medication for toothache and its associated factors in children and adolescents. Material and Methods: A cross-sectional study was carried out with 252 children/adolescents aged 6-16 years. A questionnaire was applied with questions related to demographic and socioeconomic characteristics; experience of, and self-medication for, toothache; as well as aspects related to the condition. Descriptive and inferential statistical analyses (Pearson's Chi-square test and Fisher's exact test) were performed, with a 5% significance level. Results: The prevalence of toothache was 41.7%. In 96 cases analyzed, there was prevalence of 69.8% of self-medication for toothache. There were no statistically significant associations between self-medication for toothache and variables related to the children/adolescents (gender and age), their parents or guardians (age and schooling), socioeconomic characteristics (family income and number of people in the household) and aspects related to toothache (fever, crying and school absenteeism) (p>0.05). The most commonly used drug was paracetamol (60.7%), whose choice was based to its previous use by the study population for conditions not related to toothache (47.8%). Conclusion: There was a high prevalence of self-medication for toothache in the study population. No independent variable was associated with self-medication practice.

Twist and E-cadherin deregulation might predict poor prognosis in lower lip squamous cell carcinoma.

OBJECTIVE: The aim of this study was to evaluate the expression of Twist and E-cadherin in lower lip squamous cell carcinoma (LLSCC) and their association with clinicopathologic parameters. STUDY DESIGN: Fifty-nine cases of LLSCC were analyzed by applying immunohistochemistry techniques in a semiquantitative manner. The systems proposed by Bryne etal., Brandwein-Gensler etal., and Almangush etal. were applied for analysis of the histopathologic malignancy grading system. RESULTS: Higher E-cadherin expression (general and membrane) was observed in cases presenting with disease-free survival after 5years of follow-up (P < .05). Higher Twist expression was observed in lesions classified as being in advanced stages, displaying recurrence, and having a high degree of malignancy. A significant negative correlation was detected between cytoplasmic Twist expression and membrane E-cadherin expression (P = .028). A statistically significant relationship was detected between high total Twist expression in tumors classified as high risk by Brandwein-Gensler etal., and no significant difference was observed among total, membrane, and cytoplasmic E-cadherin expressions in LLSCC cases and the 3 applied grading systems (P > .05). CONCLUSIONS: The results of the present study suggest the potential involvement of Twist and E-cadherin in the modulation of events related to worse prognoses in LLSCC cases.

Clinicopathological significance of SNPs in RAD51 and XRCC3 in oral and oropharyngeal carcinomas.

BACKGROUND: This study investigated the influence of single nucleotide polymorphisms (SNP) in RAD51 and XRCC3 on susceptibility to oral and oropharyngeal squamous cell carcinomas (SCC) and determined their clinicopathological significance. SUBJECTS AND METHODS: SNPs rs1801320 and rs1801321 in RAD51 and rs861539 in XRCC3 were genotyped in 81 patients presenting oral SCC, 45 presenting oropharyngeal SCC, and 130 healthy controls, using TaqMan allelic discrimination assays. Multiple logistic regression models were used to explore the association between SNPs and cancer development, as well as gene-gene (GxG) interaction and gene-environmental factor (GxE) interaction. Clinicopathological associations were verified through the chi-square test, and univariate and multivariate methods were applied for survival analyses. RESULTS: Although allelic and genotypic models and the GxG interaction analysis were nonsignificant, the GxE analysis revealed synergistic effects of the risk alleles of rs1801320, rs1801321, and rs861539 with smoking and alcohol consumption on susceptibility to oral and oropharyngeal SCC. Furthermore, oropharyngeal SCC patients carrying the XRCC3 rs861539 GT/TT genotype (T risk allele) presented a shorter overall survival than GG genotype carriers. CONCLUSION: Combined effects of RAD51 (rs1801320 and rs1801321) and XRCC3 (rs861539) SNPs with environmental carcinogens (tobacco and alcohol) are associated with oral and oropharyngeal SCC development.