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Penile Squamous Cell Carcinoma (PSCC) is associated with high-risk human papillomavirus (HR-HPV). The immunohistochemical (IHC) test for p16INK4a (p16) is highly correlated with HR-HPV expression in other SCCs. To investigate whether the expression of p16 IHC or HR-HPV is associated with survival in PSCC, we conducted a single institution analysis of 143 patients with a diagnosis of PSCC and, available tissue were tested for p16 IHC staining patterns, histological subtype, tumor grade, and lymphovascular invasion (LVI) by an experienced pathologist. HR-HPV status using the Cobas PCR Assay or the RNAScope high-risk HPV in situ hybridization kit were also assessed. Patient characteristics were summarized using descriptive statistics of clinico-pathologic variables. Kaplan-Meier was used to estimate median overall survival (OS), cancer specific survival (CSS) and correlated with HPV, p16, and other study variables. Patients with p16+ tumors had a significantly longer median CSS in comparison to the p16- group (p = 0.004), with respective 5-year CSS probability of 88% (95% CI; 0.84, 1) versus 58% (95% CI; 0.55, 0.76; p = 0.004). HPV status did not predict survival outcomes. Multivariable analysis with respect to OS and CSS, showed that p16+ status was associated with a lower risk of death (HR = 0.36, 95%CI; 0.20-0.67, p = 0.001), and improved CSS (HR = 0.20, 95% CI; 0.07-0.54, p = 0.002) after adjusting for covariates. In conclusion, tumor p16 status via IHC was an easy to perform independent prognostic factor for OS and CSS that correlates with HR-HPV expression.
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Recently, increased number of studies have demonstrated a relationship between the oral microbiome and development of head and neck cancer, however, there are few studies to investigate the role of oral bacteria in the context of the tumor microenvironment in a single head and neck subsite. Here, paired tumor and adjacent normal tissues from thirty-seven oral tongue squamous cell carcinoma (SCC) patients were subjected to 16S rRNA gene sequencing and whole exome sequencing (WES), in addition to RNA sequencing for tumor samples. We observed that Fusobacterium was significantly enriched in oral tongue cancer and that Rothia and Streptococcus were enriched in adjacent normal tissues. A decrease in alpha diversity was found in tumor when compared to adjacent normal tissues. While increased Fusobacterium in tumor samples was not associated with changes in immune cell infiltration, it was associated with increased PD-L1 mRNA expression. Therefore, we examined the effects of Fusobacterium on PD-L1 expression in head and neck SCC cell lines. We demonstrated that infection with Fusobacterium species can increase both PD-L1 mRNA and surface PD-L1 protein expression on head and neck cancer cell lines. The correlation between Fusobacterium and PD-L1 expression in oral tongue SCC, in conjunction with the ability of the bacterium to induce PD-L1 expression in vitro suggests a potential role for Fusobacterium on modulation of the tumor immune microenvironment in head and neck cancer.
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Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Neoplasias de la Boca , Neoplasias de la Lengua , Antígeno B7-H1/genética , Fusobacterium/genética , Fusobacterium/metabolismo , Humanos , Neoplasias de la Boca/genética , ARN Mensajero , ARN Ribosómico 16S/genética , Carcinoma de Células Escamosas de Cabeza y Cuello/genética , Neoplasias de la Lengua/genética , Microambiente Tumoral/genéticaRESUMEN
BACKGROUND: Oral cancer (OC) is usually diagnosed at advanced clinical stages due to its asymptomatic nature and absence of pathognomonic signs in its early development phase. Delayed diagnosis is one of the major causes of OC treatment failure and poor prognosis. Development of alternative diagnostic approaches are imperative for improving early detection and therapeutic success rates. Salivary cytokines (SC) have been studied as potential diagnostic biomarkers for OC and may represent a potential tool for improvement of its early detection. METHODS: In this systematic review and meta-analysis we identified SC studied as OC biomarkers by systematically reviewing the PubMed and Cochrane Library databases using the terms: "oral cancer", "cytokine", and "saliva", and also combined with "interleukin" or "interferon". Only case-control studies that measured SC by ELISA from treatment naïve patients were included in the qualitative review. For the meta-analysis were included all comparable studies that provided enough data (sample size, mean and standard deviation or standard error of the mean) for SC levels in OC patients, non-cancer controls and patients with oral potentially malignant disorders (OPMD), including leukoplakia. Comparisons with patients with oral lichen planus (OLP) and gingivitis were included in the qualitative analysis. RESULTS: A total of 28 articles (from 2004 to 2018) were included in the systematic review, describing 10 different SC, being IL-8 and IL-6 the most studied ones. SC levels were consistently higher among OC patients when compared to healthy controls and to patients with OPMD, OLP and gingivitis. Meta-analysis including 23 eligible studies showed that IL-8, IL-6, TNF-α, IL-1ß and IL-10 salivary levels were significantly higher in OC patients compared to controls; and that IL-8, IL-6, TNF-α and IL-1ß salivary levels were also higher in OC patients compared to individuals with OPMD. When compared to healthy controls, OPMD patients showed significantly higher IL-6 and TNF-α salivary levels. CONCLUSIONS: Our analyses showed that the salivary levels of some cytokines are consistently different among OC, OPMD and healthy patients, indicating that these SC may represent potential diagnostic biomarkers for OC and OPMD. Despite of that, SC levels were highly variable among studies, suggesting that further technical improvement and standardization for SC measurement by ELISA is needed in order to successfully translate these biomarkers to the clinical practice.
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Biomarcadores de Tumor/análisis , Citocinas/análisis , Detección Precoz del Cáncer/métodos , Neoplasias de la Boca/química , Saliva/química , Diagnóstico Diferencial , Ensayo de Inmunoadsorción Enzimática , Gingivitis/diagnóstico , Humanos , Leucoplasia Bucal/diagnóstico , Liquen Plano Oral/diagnóstico , Neoplasias de la Boca/diagnóstico , Lesiones Precancerosas/diagnósticoRESUMEN
OBJECTIVE: To identify salivary metabolite biomarkers to differentiate patients with oral squamous cell carcinoma and oral epithelial dysplasia (OSCC/OED) from those with persistent suspicious oral mucosal lesions (PSOML). SUBJECTS AND METHODS: Whole unstimulated saliva samples were collected from age-, sex-, and race-matched patients who had a lesion in the oral cavity and for whom open biopsies were performed. The patients included OSCC (n = 6), OED (n = 10), and PSOML (n = 32). Hydrophilic metabolites in saliva samples were comprehensively analyzed using capillary electrophoresis mass spectrometry. To evaluate the discrimination ability of a combination of multiple markers, a multiple logistic regression (MLR) model was developed to differentiate OSCC/OED from PSOML. RESULTS: Six metabolites were significantly different in OSCC/OED compared with PSOML. From these six metabolites, ornithine, o-hydroxybenzoate, and ribose 5-phosphate (R5P) were used to develop the MLR model, which resulted in a high value for the area under receiver operating characteristic curve (AUC 0.871, 95% confidential interval (CI) 0.760-0.982; p < 0.001) to discriminate OSCC/OED from PSOML. CONCLUSIONS: This is the first study to identify salivary metabolites that discriminate OSCC/OED from PSOML rather than from healthy controls. The profiles of salivary metabolites were significantly different between OSCC/OED and PSOML. The ability to discriminate OSCC/OED from PSOML is important for dentists who are not oral surgery specialists. These salivary metabolites showed potential for non-invasive screening to discriminate OSCC/OED from PSOML. CLINICAL RELEVANCE: Salivary metabolites in this study showed potential for non-invasive screening to discriminate OSCC/OED from PSOML.
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Biomarcadores de Tumor , Carcinoma de Células Escamosas , Neoplasias de la Boca , Biomarcadores de Tumor/análisis , Carcinoma de Células Escamosas/diagnóstico , Femenino , Humanos , Hiperplasia/diagnóstico , Masculino , Neoplasias de la Boca/diagnóstico , Saliva/químicaRESUMEN
PURPOSE: This study evaluated the discriminatory power of salivary transcriptomic and proteomic biomarkers in distinguishing oral squamous cell carcinoma cases from controls and potentially malignant oral disorders (PMOD). EXPERIMENTAL DESIGN: A total of 180 samples (60 OSCC patients, 60 controls, and 60 PMOD patients) were used in the study. Seven transcriptomic markers (IL8, IL1ß, SAT1, OAZ1, DUSP1, S100P, and H3F3A) were measured using qPCR, and two proteomic markers (IL8 and IL1ß) were evaluated by ELISA. RESULTS: Among 7 transcriptomic markers, transcript level of DUSP1 was significantly lower in OSCC patients than in controls and PMOD patients. Between the proteomic markers, the protein concentration of IL8 and IL1ß was significantly higher in OSCC patients than controls and dysplasia patients. Univariate fractional polynomial (FP) models revealed that salivary IL8 protein (IL8p) has the highest AUC value between OSCC patients and controls (0.74) and between OSCC and PMOD patients (0.72). Applying a 2-marker FP model, salivary IL8p combined with IL1ß gave the best AUC value for discrimination between OSCC patients and controls, as well as the IL8p combined with H3F3A mRNA, which gave the best AUC value for discrimination between OSCC and PMOD patients. Multivariate models analysis combining salivary analytes and risk factor exposure related to oral carcinogenesis formed the best combinatory variables for differentiation between OSCC versus PMOL (AUC = 0.80), OSCC versus controls (AUC = 0.87), and PMOD versus controls (AUC = 0.78). CONCLUSIONS: The combination of transcriptomic and proteomic salivary markers is of great value for oral cancer detection and differentiation from PMOD patients and controls. Clin Cancer Res; 22(13); 3340-7. ©2016 AACR.
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Biomarcadores de Tumor/química , Carcinoma de Células Escamosas/diagnóstico , Fosfatasa 1 de Especificidad Dual/análisis , Neoplasias de Cabeza y Cuello/diagnóstico , Interleucina-1beta/análisis , Interleucina-8/análisis , Neoplasias de la Boca/diagnóstico , Saliva/química , Adulto , Anciano , Detección Precoz del Cáncer/métodos , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proteómica/métodos , Factores de Riesgo , Carcinoma de Células Escamosas de Cabeza y Cuello , TaiwánRESUMEN
O carcinoma epidermóide de boca (CEB) é uma neoplasia agressiva, causadora de alta morbidade e mortalidade. Uma de suas características clínicas mais importantes é a disseminação tumoral levando a uma doença metastática nos linfonodos regionais. Entretanto, limitações relacionadas às tecnologias diagnósticas atualmente disponíveis fazem com que a detecção da metástase linfonodal ainda seja um grande desafio clínico. Assim, melhorias na capacidade de predição de potencial metastático e/ou na detecção precoce e precisa da doença linfonodal possibilitariam determinar quais pacientes, de fato, se beneficiariam da abordagem cirúrgica cervical. Ao mesmo tempo, preservaria os portadores de tumores menos agressivos (não-metastáticos), reduzindo a morbidade e levando à maior sobrevida. Neste estudo investigamos padrões de expressão gênica tumoral determinados a partir do sequenciamento em larga escala do transcriptoma, comparando, por RNA-Seq, 10 CEB pequenos, mas já metastáticos (T1N+), com 10 CEB grandes, mas não-metastáticos (T3/T4N0). Análises de bioinformática sugeriram 150 genes diferencialmente expressos (DE) com potencial de separar os dois grupos de estudo. O valor preditivo destes genes foi desafiado in silico com dados do The Cancer Genome Atlas (TCGA), seguido de validação técnica nas mesmas amostras sequenciadas e, finalmente, validação biológica a partir de amostras independentes de CEB. Nossos resultados indicaram o NR3C2 como um potencial biomarcador de metástase nodal e sugerem que a regulação de canais iônicos pode ter um papel importante no processo metastático do CEB. Embora mais estudos sejam necessários, nossos resultados indicam que no futuro marcadores transcricionais poderão ser usados no diagnóstico e predição da ocorrência de doença metastática linfonodal em pacientes com CEB, promovendo melhorias na abordagem terapêutica.
Oral squamous cell carcinoma (OSCC) is an aggressive disease related to high morbidity and mortality. Lymph node metastasis is one of the main prognostic factors for OSCC patients, but no reliable diagnostic methods are available to accurately diagnose metastatic disease. Improvements in diagnosis of metastasis would enhance the indication of neck surgery for lymph nodes resection, sparing patients with locally restricted disease. In this study, we aimed to investigate if differences in the pattern of gene expression would help to diagnose metastatic OSCC. For this, we sequenced the transcriptome of 10 small (T1) metastatic and 10 large (T3-T4) nonmetastatic OSCC aiming to determine differentially expressed transcripts (DET). Our results showed 150 DET with potential to separate metastatic and non-metastatic OSCC cases. This set of 150 genes were challenged through an in silico approach using data from The Cancer Genome Atlas (TCGA). Validated genes were then confirmed by RT-qPCR using the same set of sequenced samples followed by another confirmation in an independent set of OSCC cases. The transcript NR3C2 was found as a putative biomarker for lymph node metastasis. Pathway analysis indicated that transcriptional alterations related to ion channels pathways may be involved in the biology of metastasis in OSCC. Although our results are not definitive, it indicates that transcriptional markers would be useful to diagnose or predict lymph node metastatic disease in OSCC patients, potentially improving therapeutic approaches.
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Humanos , Carcinoma de Células Escamosas , Expresión Génica , Metástasis de la Neoplasia , Neoplasias de la Boca/complicaciones , Secuenciación de Nucleótidos de Alto RendimientoRESUMEN
BACKGROUND: Today there are more than 2 billion alcohol users and about 1.3 billion tobacco users worldwide. The chronic and heavy use of these two substances is at the heart of numerous diseases and may wreak havoc on the human oral microbiome. This study delves into the changes that alcohol and tobacco may cause on biofilms of the human oral microbiome. To do so, we used swabs to sample the oral biofilm of 22 subjects; including 9 control-individuals with no or very low consumption of alcohol and no consumption of tobacco, 7 who were chronic and heavy users of both substances and 6 active smokers that reported no significant alcohol consumption. DNA was extracted from swabs and the V1 region of the 16S rRNA gene was PCR amplified and sequenced using the Ion Torrent PGM platform, generating 3.7 million high quality reads. DNA sequences were clustered and OTUs were assigned using the ARB SILVA database and Qiime. RESULTS: We found no differences in species diversity and evenness among the groups. However, we found a significant decrease in species richness in only smokers and in smokers/drinkers when compared to controls. We found that Neisseria abundance was significantly decreased in both groups when compared to controls. Smokers had significant increases in Prevotella and Capnocytophaga and reductions in Granulicatella, Staphylococcus, Peptostreptococcus and Gemella when compared to the two other groups. Controls showed higher abundance of Aggregibacter, whilst smokers/drinkers had lower abundances of Fusobacteria. Samples from only smokers clustered closer together than to controls and smokers/drinkers, and also had a significant reduction in inter-group dissimilarity distances, indicating a more homogenous group than controls. CONCLUSIONS: Our results indicate that the continued use of tobacco or alcohol plus tobacco significantly reduces bacterial richness, which apparently leads to a reduction in inter-group variability, turning the respective biofilms into a more homogenous microenvironment in terms of bacterial community composition, with possible consequences for human oral diseases.
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Consumo de Bebidas Alcohólicas , Bacterias/clasificación , Biopelículas/crecimiento & desarrollo , Biota/efectos de los fármacos , Mucosa Bucal/microbiología , Uso de Tabaco , Anciano , Bacterias/genética , Bacterias/aislamiento & purificación , Análisis por Conglomerados , ADN Bacteriano/química , ADN Bacteriano/genética , ADN Ribosómico/química , ADN Ribosómico/genética , Femenino , Humanos , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Filogenia , Reacción en Cadena de la Polimerasa , ARN Ribosómico 16S/genética , Análisis de Secuencia de ADNRESUMEN
This study sought to assess and compare retrospective demographic and clinical data of oral lesions of lichen planus, pemphigus vulgaris, and mucous membrane pemphigoid from the records of the Department of Oral Pathology and Surgery, School of Dentistry, Universidade Federal de Minas Gerais, Brazil, covering a period of 55 years. Out of 25,435 specimens, these immunologically-mediated diseases accounted for 301 (1.18%) cases, of which 250 (0.98%) were lichen planus, 27 (0.11%) were pemphigus vulgaris, and 24 (0.09%) were mucous membrane pemphigoid. Lichen planus presented mainly as white asymptomatic plaques on buccal mucosa. Pemphigus vulgaris was usually characterized by multiple symptomatic erithematous ulcers on the buccal mucosa. Painful ulcers and/or blisters on the gingiva were the most common presentation for mucous membrane pemphigoid. Desquamative gingivitis was noted for all 3 diseases, but mainly for mucous membrane pemphigoid. Overall, lesions were more frequent in white women >50 years. Oral manifestations of immunologically-mediated diseases are relatively rare, and the correct diagnosis can be a challenge for dentists as the lesions often share similar clinical and demographic features.
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Liquen Plano Oral/patología , Enfermedades de la Boca/patología , Penfigoide Benigno de la Membrana Mucosa/patología , Pénfigo/patología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Brasil/epidemiología , Niño , Femenino , Humanos , Liquen Plano Oral/diagnóstico , Liquen Plano Oral/epidemiología , Masculino , Persona de Mediana Edad , Boca/patología , Enfermedades de la Boca/diagnóstico , Enfermedades de la Boca/epidemiología , Penfigoide Benigno de la Membrana Mucosa/diagnóstico , Penfigoide Benigno de la Membrana Mucosa/epidemiología , Pénfigo/diagnóstico , Pénfigo/epidemiología , Estudios Retrospectivos , Adulto JovenRESUMEN
OBJECTIVES: To compare the immunohistochemistry (IHC) expression of epidermal growth factor receptor (EGFR) in oral squamous cell carcinomas (OSCC) with the gene amplification evaluated by fluorescence in situ hybridization (FISH) and chromogenic in situ hybridization (CISH) and their association with clinicopathological parameters. Additionally, we tested the sensibility and specificity of CISH in comparison with FISH. DESIGN: Case series study SETTING: Oral surgery and pathology department in a school of dentistry. PARTICIPANTS: 52 patients with histopathological diagnosis of OSCC. METHODS: Tumour tissue samples from 52 patients with OSCC were evaluated by IHC, FISH and CISH using tissue microarray technology. Clinicopathological data from all patients were collected. RESULTS: EGFR+ rates were 53.8% (28/52) by IHC, 5.8% (3/52) by CISH and 15.4% (8/52) by FISH. Amplification detected by CISH and FISH with IHC negative occurred in 3.8% (2/52), and one case (1.9%) showed amplification detected by CISH and FISH and protein overexpression concomitantly. There were 9.6% FISH+ cases with IHC and CISH negative rates and 6/8 (75%) FISH+ and also EGFR+ cases; however, an association between protein expression and gene amplification was not found for both techniques. IHC and FISH rates were not associated with clinicopathological features. CISH+ rates were associated with T3-T4 status. Compared with FISH assay, CISH reached a sensitivity of 37.5% and specificity of 100%. CONCLUSIONS: There is no association between EGFR expression and gene amplification in OSCC when the IHC is driven to external epitopes of the protein. Although CISH demonstrates specificity, technical problems may influence sensibility when compared with FISH.
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OBJECTIVES: The objective of this study was to comparatively evaluate the density of lymphatic vessels (LVD) and neoformed microvessels (NMVD) in squamous cell carcinoma of the oral cavity (OCSCC) and lip (LSCC). Association between LVD/NMVD and vascular endothelial growth factor (VEGF)-A/-C was also assessed. STUDY DESIGN: OCSCC and LSCC were compared with regard to immunoexpression of LVD, NMVD, and vascular endothelial growth factor-A (VEGF)-A/-C. Association between VEGF-A/-C with vascularity was also assessed. Statistical analyses were performed using t test, Pearson χ(2), and Mann-Whitney tests. Statistical significance was accepted at P less than .05. RESULTS: The NMVD and VEGF-C expressions were significantly higher in OCSCC compared with LSCC. NMVD was associated with VEGF-C in OCSCC, but not in LSCC. CONCLUSIONS: Differences in NMVD and VEGF-C were found between OCSCC and LSCC. Positive association between VEGF-C and NMVD was observed in OCSCC, but not in LSCC, which may be one of the contributing factors that account for the distinctive clinical-biological behavior of these lesions.
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Carcinoma de Células Escamosas/irrigación sanguínea , Microvasos/patología , Neoplasias de la Boca/irrigación sanguínea , Neovascularización Patológica , Biomarcadores de Tumor/análisis , Carcinoma de Células Escamosas/metabolismo , Distribución de Chi-Cuadrado , Femenino , Humanos , Neoplasias de los Labios/irrigación sanguínea , Neoplasias de los Labios/metabolismo , Vasos Linfáticos/patología , Masculino , Persona de Mediana Edad , Suelo de la Boca/irrigación sanguínea , Suelo de la Boca/metabolismo , Neoplasias de la Boca/metabolismo , Estadísticas no Paramétricas , Neoplasias de la Lengua/irrigación sanguínea , Neoplasias de la Lengua/metabolismo , Factor A de Crecimiento Endotelial Vascular/biosíntesis , Factor C de Crecimiento Endotelial Vascular/biosíntesisRESUMEN
BACKGROUND: Mucoepidermoid carcinoma is the most common malignant tumor of salivary glands. This tumor is characterized by a great variability in clinical behavior, and little is known about the pathological mechanisms involved in its variance. Angiogenesis is an important step in tumor progression and is believed to be an essential event for metastatic dissemination. METHODS: We aimed to investigate angiogenesis and lymphangiogenesis in mucoepidermoid carcinoma measuring the density of neoformed and lymphatic vessels using CD105 and D2-40 antibodies, respectively, and by immunohistochemical evaluation of VEGF-A and VEGF-C proteins. It was also investigated the expression of D2-40 in neoplastic cells. RESULTS: We studied 26 cases of mucoepidermoid carcinoma, which showed great angiogenic activity measured by neoformed vessel density. However, a low density of lymphatics was observed. VEGF-A, VEGF-C, and D2-40 were commonly detected in mucoepidermoid carcinoma, but only VEGF-A expression correlated with neoformed vessel density. Recurrence and nodal metastasis were associated with low VEGF-A expression and low neoformed vessel density, indicating that impaired angiogenesis could lead to an aggressive phenotype. CONCLUSIONS: Angiogenesis seems important in the modulation of mucoepidermoid carcinoma pathogenesis; however, none of the parameters analyzed could predict tumor behavior.
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Carcinoma Mucoepidermoide/patología , Linfangiogénesis/fisiología , Neovascularización Patológica/patología , Neoplasias de las Glándulas Salivales/patología , Glándulas Salivales Menores/patología , Adulto , Anticuerpos Monoclonales de Origen Murino/análisis , Antígenos CD/análisis , Biomarcadores de Tumor/análisis , Carcinoma Mucoepidermoide/irrigación sanguínea , Carcinoma Mucoepidermoide/secundario , Causas de Muerte , Endoglina , Femenino , Humanos , Metástasis Linfática/patología , Vasos Linfáticos/patología , Masculino , Microvasos/patología , Clasificación del Tumor , Recurrencia Local de Neoplasia/patología , Receptores de Superficie Celular/análisis , Neoplasias de las Glándulas Salivales/irrigación sanguínea , Glándulas Salivales Menores/irrigación sanguínea , Tasa de Supervivencia , Factor A de Crecimiento Endotelial Vascular/análisis , Factor C de Crecimiento Endotelial Vascular/análisisRESUMEN
The objective of this study was to evaluate lymphangiogenesis in oral squamous cell carcinoma and in the associated lymph nodes and podoplanin expression in neoplastic cells at the invasive front. In addition, the association of the above parameters with lymph node metastasis was also investigated. We used immunohistochemistry to examine primary tumors and lymph nodes, regardless of metastasis. Lymphatic vessel density (LVD) and microvessel density (MVD) were assessed by antibodies D2-40 and CD105, respectively, in intratumoral and peritumoral areas and in lymph node regions. Vascular endothelial growth factor-C and vascular endothelial growth factor receptor-3 expression was evaluated in tumor cells and D2-40 (podoplanin) expression in parenchymal cells found at the invasive front. The majority of cases with nodal involvement presented a high peritumoral LVD. In addition, a strong association of LVD with size and site of primary tumors could also be identified. MVD was statistically associated with metastasis, and a significant association between the lymphangiogenic factors and the density of vessels in the intratumoral region was also seen. The well-differentiated tumors did not express podoplanin. LVD and MVD were higher in metastatic lymph nodes than in nonmetastatic lymph nodes. The enhanced vascular network in metastatic lymph nodes reinforces the previous reports of lymphangiogenesis occurrence in lymph nodes. Moreover, the expression of podoplanin by more undifferentiated tumor cells suggests that this protein could be an indicator of tumor aggressiveness.
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Carcinoma de Células Escamosas/patología , Ganglios Linfáticos/metabolismo , Linfangiogénesis , Metástasis Linfática , Glicoproteínas de Membrana/metabolismo , Neoplasias de la Boca/patología , Adulto , Carcinoma de Células Escamosas/metabolismo , Femenino , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Neoplasias de la Boca/metabolismoRESUMEN
OBJECTIVES: To investigate the immunoexpression of epidermal growth factor receptor (EGFR) in a sample of oral leukoplakias (OL) and to determine the receptor' s association with dysplasia, tobacco consumption, lesion site, and proliferation rate. Although EGFR should be overexpressed in some oral leukoplakias, the factors that may interfere with this expression and the influence of this receptor on epithelial proliferation have yet to be investigated. STUDY DESIGN: Samples of oral leukoplakias (48) and of normal oral epithelium (10) were immunohistologically examined for expression of EGFR. Immunohistochemistry for Ki-67, and p27 were also performed in leukoplakias. EGFR expression was associated with clinical and pathological features. RESULTS: EGFR was positive in 62.5% of the leukoplakias and 50% of normal oral epithelium. The number of EGFR positive OL located in high-risk sites was significantly higher than EGFR positive OL located in low-risk sites. Most of the p27 negative leukoplakias were EGFR positive, and the p27 index in the parabasal layer was diminished in the presence of dysplasia. Positivity for EGFR was not associated with dysplasia, tobacco exposure, or Ki-67. CONCLUSION: EGFR is expressed in leukoplakia regardless of dysplasia, but EGFR positivity should be more frequent in lesions sited in areas of high cancer risk. The association between EGFR and p27 may represent an important mechanism in the control of cellular proliferation and malignant progression of oral epithelium and therefore warrants further investigation.
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Receptores ErbB/biosíntesis , Leucoplasia Bucal/metabolismo , Leucoplasia Bucal/patología , Adulto , Anciano , Proliferación Celular , Femenino , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
The objective of this research was to investigate the salivary levels of epidermal growth factor (EGF) in patients with oral squamous cell carcinoma (OSCC) in comparison with clinically healthy individuals and to verify the immunoexpression of EGF in tumor samples. In addition, the relationship between salivary levels and tumoral EGF expression with clinicopathologic features was investigated. We carried out an investigation on EGF expression in lesion samples and in saliva of OSCC patients through immunohistochemistry and enzyme-linked immunosorbent assay, respectively. EGF salivary levels of OSCC patients were also compared with levels in saliva of healthy controls. EGF levels were significantly lower in OSCC patients in comparison with the control group. Smoking, tumor location, and alcohol consumption affected salivary levels of EGF. Strong immunoexpression of EGF was associated with a more aggressive histologic pattern of the lesion. There was no significant association among salivary levels and immunohistochemical expression of EGF. Although EGF expression is frequently observed in tumors, salivary levels of EGF are reduced in patients with OSCC samples. Tobacco and alcohol may decrease EGF in saliva, which may contribute to oral carcinogenesis. Indeed, further investigations are needed to elucidate the EGF pathways.
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Carcinoma de Células Escamosas/diagnóstico , Factor de Crecimiento Epidérmico/metabolismo , Neoplasias de la Boca/diagnóstico , Boca/metabolismo , Saliva/metabolismo , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Consumo de Bebidas Alcohólicas , Biomarcadores/metabolismo , Carcinoma de Células Escamosas/inmunología , Carcinoma de Células Escamosas/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Boca/inmunología , Boca/patología , Neoplasias de la Boca/inmunología , Neoplasias de la Boca/patología , Pronóstico , Factores de Riesgo , FumarRESUMEN
PURPOSE: To verify the aesthetic impact of mild and moderate dental fluorosis on young adult students from the UFMG using pictures with different fluorosis levels simulated in a computer program. MATERIALS AND METHODS: The sample consisted of 396 university students, randomly selected from various courses (except dentistry). These participants were shown three mouth pictures with different rates of dental fluorosis (TFO, TF2 and TF4) according to the Thylstrup-Fejerskov Index (TF). The volunteers gave an individual assessment of the pictures and graded them (from 1 to 10) based on their aesthetics. In addition, they answered if they would feel uncomfortable smiling and if they would seek dental treatment in each case. The results were submitted to a chi-square test (P < 0.05). RESULTS: The students preferred the TF4 picture to the TF2. The picture which presented no fluorosis was more often preferred than the pictures which presented some form of change due to fluorosis. Higher scores were recorded by men for the TF2 picture than by women (P < 0.05). As for the TF0 and TF4 pictures, the scores were similar among males and females. Furthermore, women reported more discomfort in smiling (P = 0.001) and a greater desire to seek out dental treatment than did men. Only 27.5% of all students stated that they knew what dental fluorosis was. CONCLUSION: Mild and moderate dental fluorosis had a negative aesthetic effect on the studied population, leading to a strong desire to seek dental treatment to change the appearance of affected teeth.
Asunto(s)
Estética Dental , Fluorosis Dental/psicología , Estudiantes/psicología , Distribución de Chi-Cuadrado , Gráficos por Computador , Femenino , Humanos , Entrevistas como Asunto , Masculino , Percepción , Fotografía Dental , Tamaño de la Muestra , Autoimagen , Encuestas y Cuestionarios , Universidades , Adulto JovenRESUMEN
El síndrome de boca ardiente (SBA) es una enfermedad crónica que se caracteriza por una sensación de quemazón de la mucosa bucal, que impresiona clínicamente normal. Es una entidad nosológica frecuente, sin embargo, los mecanismos implicados en su desarrollo en la actualidad son poco conocidos. El objetivo de este trabajo fue llevar a cabo una revisión de la literatura sobre dicho síndrome y se hizo énfasis en sus principales factores etiológicos y en el tratamiento de esta enfermedad. El SBA es una afección multifactorial compleja, debido a la diversidad de sus síntomas, dificultad en el tratamiento y las características psicológicas particulares de los pacientes. El diagnóstico correcto es el elemento principal para establecer el tratamiento. Es necesario realizar nuevas investigaciones para aclarar con precisión las causas del SAB, especialmente en la forma primaria(AU)
Burning mouth syndrome (BMS) is a chronic condition characterized by burning sensation on a clinic normal oral mucosa. BMS is not a rare condition, however, mechanisms involved in their development remains poorly understood. The aim of this paper was to carry out a review of literature about this syndrome, highlighting the main etiological factors as an approach to the management of this condition(AU)
Asunto(s)
Humanos , Síndrome de Boca Ardiente/diagnóstico , Síndrome de Boca Ardiente/terapia , Síndrome de Boca Ardiente/epidemiología , Síndrome de Boca Ardiente/etiología , Literatura de Revisión como Asunto , Mucosa Bucal/lesionesRESUMEN
OBJECTIVE: Salivary gland disorders in patients with chronic hepatitis C (CHC) have been considered oral extrahepatic manifestations, reinforcing the hepatitis C virus (HCV) as a sialotropic virus. Hence, the authors investigated the prevalence of HCV RNA in saliva and salivary glands and its possible association with xerostomia, hyposalivation and sialadenitis in patients with CHC. PATIENTS AND METHODS: In 65 patients with confirmed CHC, the HCV RNA was investigated by nested RT-PCR in saliva samples and minor salivary glands. Xerostomia, hyposalivation, clinical and histopathological evidence of sialadenitis were also evaluated. Univariate and multivariate analyses were employed to verify associations. RESULTS: HCV RNA was detected in the saliva of 26/65 (40.0%) patients and in 12/65 (18.5%) salivary glands. Xerostomia was reported by 23/65 (35.4%) patients, and hyposalivation was diagnosed in 13/65 (20.0%) patients. Sialadenitis was confirmed by histopathological features in 31/65 (47.7%) patients. Twelve (38.7%) of the 31 patients with sialadenitis presented HCV RNA in saliva and 2/31 (6.5%) in salivary glands. No associations were found between xerostomia, hyposalivation or sialadenitis and the detection of HCV RNA in saliva or in salivary glands. CONCLUSIONS: Although xerostomia, hyposalivation and sialadenitis are frequent findings in CHC patients, our study did not confirm the association between the detection of HCV RNA in saliva or salivary glands with these salivary gland disorders. However, an indirect role of HCV by immune-mediated virus mechanisms in the pathogenesis of salivary gland disorders in this group of patients cannot be ruled out.