Carcinoma de células escamosas y el rol discutido de la irritación mecánica crónica. Informe de un caso / Squamous oral cell carcinoma and the discussed role of chronic mechanical irritation. Report of a case

Resumen Objetivo Describir el desarrollo de un carcinoma oral de células escamosas, en el que la irritación mecánica crónica aparenta tomar un rol protagonista en la carcinogénesis. Caso clínico Un paciente de 41 años de edad, argentino, con antecedentes de fisura labio alvéolo palatina, diabetes mellitus, convulsiones, consumo de cocaína y marihuana, enolismo crónico y tabaquismo, acude al Servicio de Odontología del Hospital Central de Mendoza para la evaluación de una úlcera dolorosa en el dorso de su lengua, de varias semanas de evolución, en íntima relación con un primer premolar superior derecho y una pieza supernumeraria. Se realizó una biopsia y de la anatomía patológica resultó el diagnóstico de carcinoma oral de células escamosas. Se ofreció al paciente posibles tratamientos que rechazó, por lo que se inició terapia paliativa y sintomática. Al avanzar su mal estado general, falleció por complicaciones relacionadas a la deglución. Si bien no está definido el rol de la irritación mecánica crónica en la etiología de la carcinogénesis, ejerce un efecto promotor del daño causado por el tabaco y el alcohol. Si bien el paciente era fumador y bebía alcohol, se puede observar que desarrolló un carcinoma de células escamosas en evidente relación a un trauma crónico, ya que la lesión en la cara dorsal de lengua está en íntimo contacto con el factor irritante. Aun así, la evidencia actual disponible es limitada y discute el protagonismo del trauma crónico por lo que se necesitan más estudios para evaluar y definir la posible relación causal de la irritación mecánica crónica en la carcinogénesis.

Abstract Aim To describe the development of an oral squamous cell carcinoma, in which chronic mechanical irritation appears to play a significant role in carcinogenesis. Clinical case A 41-year-old patient, from Argentina, with a history of cleft lip and palate, diabetes mellitus, seizures, cocaine and cannabis use, chronic alcoholism and smoking, comes to the Dentistry Service of the Central Hospital for the evaluation of a painful ulcer on the dorsum of the tongue, which had been developing for several weeks, in close relation to an upper right first premolar and a supernumerary tooth. A biopsy was performed, and the pathological anatomy resulted in the diagnosis of oral squamous cell carcinoma. Possible treatments were offered to the patient, which he rejected, so palliative and symptomatic therapy was initiated instead. As his poor general condition progressed, he died due to complications related to swallowing. Although the role of chronic mechanical irritation in the development of carcinogenesis is not yet fully defined, it has been shown to have a promoting effect on the damage caused by tobacco and alcohol. Although the patient was a smoker and drank alcohol, it can be observed that he developed a squamous cell carcinoma in obvious relation to a chronic trauma, since the lesion develops on the dorsal face of the tongue in close contact with the irritant factor. Still, the current evidence available is limited and discusses the role of chronic trauma, so more studies are needed to evaluate and define the possible causal relationship of chronic mechanical irritation in the development of carcinogenesis.

Immunoexpression of ALDH1A1, FGFR2, CD44 and Caspase-3 in Oral Squamous Cell Carcinoma and Leukoplakia: A pilot study

Current research highlighted the importance to recognize feasible biomarkers for early diagnoses and treatment in oral cancer. Our study analyzed the expression and spatial distribution of ALDH1A1, FGFR2, caspase-3, and CD44 in Oral Squamous Cell Carcinoma (OSCC) and leukoplakia with and without oral mucosal dysplasia. Paraffin-embedded samples of OSCC (n=5), leukoplakia with (n=5) and without (n=5) dysplasia obtained by incisional biopsies were processed using conventional histochemical techniques. Immunohistochemistry was performed using antibodies against ALDH1A1, FGFR2, caspase-3, and CD44. Images of the immunohistochemically stained tissue sections were analyzed according to the intensity of the immunostaining of each marker and classified in Scores. The Kruskal- Wallis test was performed (p≤0.05). Our results demonstrated a statically difference in the expression of all immunomarkers between OSCC and leukoplakia without dysplasia, being more significant in FGFR2 and ALDH1A1. Within the limitations of this study, our data showed that all biomarkers were overexpressed in OSCC and leukoplakia with oral mucosa dysplasia, suggesting that the presence of dysplasia is a significant clinic-pathologic predictor for malignant transformation.

La actual evidencia científica enfatiza la importancia de reconocer biomarcadores viables para el diagnóstico y tratamiento temprano del cáncer oral. Nuestro estudio piloto analizó la expresión y distribución espacial de ALDH1A1, FGFR2, caspasa-3 y CD44 en carcinoma oral de células escamosas (COCE) y en leucoplasia con o sin displasia de la mucosa oral. Las muestras incluidas en parafina de COCE (n=5), con (n=5) y sin (n=5) displasia fueron obtenidas mediante biopsias incisionales, las cuales se procesaron utilizando técnicas histoquímicas convencionales. El análisis inmunohistoquímico se realizó utilizando anticuerpos contra ALDH1A1, FGFR2, caspasa-3 y CD44. Las imágenes de las secciones de cada muestra fueron analizadas según la intensidad de inmunoexpresión de cada marcador y se clasificaron en diferentes escalas (scores). Se realizó la prueba de Kruskal-Wallis (valores de p<0,05). Nuestros resultados demostraron una diferencia estadística en la expresión de todos los inmunomarcadores entre COCE y las muestras con leucoplasia sin displasia, siendo más significativa en FGFR2 y ALDH1A1. Considerando las limitaciones de este estudio, los datos sugieren que la presencia de displasia en la mucosa oral es un importante predictor clínico-patológico de transformación maligna.

Experimental carcinogenesis with 7, 12-dimethylbenz(a)anthrazene (DMBA) and its inhibition with isothi-ocyanates / Carcinogénesis experimental con 7, 12-dimetilbenzantraceno (DMBA) y su inhibición con isitiocianatos

Introduction: DMBA is a chemical carcinogen that induces carcinomas within a few weeks of its application. We developed an experimental model of carcinogenesis induced by DMBA dissolved in 0,5% paraffin oil (DMBA-PO), verifying the inhibitory effect of the carcinogenicity of phenyl isothiocyanate (PhITC), phenethyl (PhnITC) and benzyl isothiocyanate (BITC). Material and Methods: For this, 88 hamsters were distributed into three groups: one exposed to DMBA-PO (Group 1, n=12), three subgroups (n=12) exposed to PhITC, PhnITC, BITC and DMBA-PO (Group 2, n=36) and four control subgroups (n=10) that were not exposed to the carcinogen in which PO (paraffin oil) and isothiocyanates were applied (Group 3, n=40). Results: The experiment had a duration of 20 weeks, at the end of which the inhibitory effect was established by comparing the lesions developed in the groups that received isothiocyanates with the group that was only treated with DMBA-PO. The carcinogenic effect of DMBA-PO is 100% (35 carcinomas) and the inhibitory effect was 0, whereas in the presence of isothiocyanates the carcinogenic effect decreases, with an inhibitory effect of 86% for BITC (5 carcinomas) and 74% for PhITC (9 carcinomas). Conclusion: The inhibitory effect for PhnITC is 80% in relation to invasive OSCC (1 carcinoma).

Introducción: El DMBA es un carcinógeno químico que induce carcinomas a las pocas semanas de su aplicación. Desarrollamos un modelo experimental de carcinogénesis inducida por DMBA disuelto en aceite de parafina al 0,5% (DMBA-Ap) comprobando el efecto inhibidor de la carcinogénesis de los isotiocianatos fenil (PhITC), fenetil (PhnITC) y bencil isotiocianato (BITC). Material y Métodos: Para ello, se distribuyeron 88 hámsteres en 3 grupos: uno expuesto al DMBA-Ap (Grupo 1, n=12), tres subgrupos (n=12) expuestos a PhITC, PhnITC, BITC y DMBA-Ap (Grupo 2, n=36) y cuatro subgrupos controles (n=10), no expuestos al carcinógeno en el que se aplicaron Ap e isotiocianatos (Grupo 3, n=40). Resultados:El experimento tuvo una duración de 20 semanas, al final de la cual se establece de forma comparativa el efecto inhibidor comparando las lesiones desarrolladas en los grupos que recibieron isotiocianatos con respecto al grupo tratado sólo con DMBA-Ap. El efecto carcinógeno del DMBA-Ap es del 100% (35 carcinomas) y el efecto inhibidor 0, mientras que en presencia de isotiocianatos el efecto carcinógeno disminuye, con un efecto inhibidor del 86% para BITC (5 carcinomas) y del 74% para el PhITC (9 carcinomas). Conclusión:El efecto inhibidor del PhnITC es del 80% en relación con el COCE invasivo (1 carcinoma).

Pro-and Anti-inflammatory Biomarkers as Potential Prognosis Markers in Oral Squamous Cell Carcinoma

ABSTRACT: The most widely used method to classify prognostic factors in cancers today is TNM. However, Oral Squamous Cell Carcinoma (OSCC) often demonstrates different behaviors in relation to aggressiveness and therapeutic response at the same TNM stage. So, in such cases biomarkers can be used to identify the biological diversity of these tumors more reliably, leading to better therapeutic strategies and disease management. The presence of inflammatory immune cells in the tumor microenvironment can have pro or antitumor effects and the investigation of the expression of inflammatory markers in OSSC can be usefulto design immunotherapeutic interventions. The Transforming Growth Factor alpha is a potent stimulator of cell migration that acts on cell proliferation, invasion and metastasis of cancer, as well as immune suppression and angiogenesis. Inflammatory cytokines, such as Interferon-gamma, mediate macrophage differentiation. Macrophages are an important component of the OSCC microenvironment. The greater amount of tumor-associated macrophages, especially the M2 phenotype, may be associated with a more aggressive biological behavior of the OSCC and, consequently, with reduced survival.

RESUMEN: El método más utilizado para clasificar los factores de pronóstico en los cánceres en la actualidad es TNM. Sin embargo, el carcinoma oral de células escamosas (COCE) a menudo muestra diferentes comportamientos en relación con la agresividad y la respuesta terapéutica en la misma etapa TNM. Entonces, en tales casos, los biomarcadores pueden usarse para identificar la diversidad biológica de estos tumores de manera más confiable, lo que lleva a mejores estrategias terapéuticas y manejo de la enfermedad. La presencia de células inmunes inflamatorias en el microambiente tumoral puede tener efectos pro o antitumorales y la investigación de la expresión de marcadores inflamatorios en COCE puede ser útil para diseñar intervenciones inmunoterapéuticas. El factor de crecimiento transformante α es un potente estimulador de la migración celular que actúa sobre la proliferación celular, la invasión y metástasis del cáncer, así como la inmunosupresión y la angiogénesis. Las citocinas inflamatorias, como el IFN-γ, median en la diferenciación de macrófagos. Los macrófagos son un componente importante del microambiente COCE. La mayor cantidad de macrófagos asociados a tumores, especialmente el fenotipo M2, puede estar asociada a un comportamiento biológico más agresivo del COCE y, en consecuencia, a una menor supervivencia.

Avaliação in vitro e in silico da atividade do S-(-)-Álcool Perílico sobre linhagens celulares do Carcinoma Epidermóide de Língua / In vitro and in silico evaluation of the activity of S-(-)-Peryllic Alcohol on Tongue Squamous Carcinoma cell lines

O carcinoma epidermóide oral (CEO) é a neoplasia maligna mais frequente da cavidade oral e constitui um problema de saúde pública devido a sua alta taxa de incidência e mortalidade devido em muitos casos ao fracasso terapêutico e a resistência tumoral. Assim sendo, destaca-se a busca por novas moléculas biologicamente ativas, como as encontradas nos produtos de origem natural. Este trabalho tem como objetivo avaliar a atividade antineoplásica do S-(-)-álcool perílico (POH) em culturas de células de CEO de língua e predizer sua afinidade através de modelo computacional sobre proteínas que regulam o ciclo celular. Para isso, foram utilizadas duas linhagens celulares de CEO de língua, HSC-3 e SCC-25. Os seguintes grupos foram analisados: G0 (controle; células cultivadas na ausência de POH), G1 (células tratadas com cisplatina a 40 µM), G2 (células tratadas com POH a 0,5 mM), G3 (células tratadas com POH a 1,0 mM), G4 (células tratadas com POH a 1,5 mM) e G5 (células tratadas com POH a 3,0 mM). Diferenças entre estes grupos foram investigadas através dos seguintes ensaios: viabilidade celular (Alamar Blue e Live/Dead assay) e atividade migratória (Wound healing). Foi também realizada a predição de afinidade entre o POH e as moléculas de controle do ciclo celular utilizando a docagem molecular com emprego do software Molegro Virtual Docker, v. 6.0.1. Os dados foram tratados estatisticamente pelo GraphPad Prism 6.0 (GraphPad Software, EUA), análises paramétricas utilizando teste Anova, pós-teste de Tukey e teste estatístico não-paramétricos de Kruskal-Wallis, seguido pelo teste t de estudent foram adotados para determinação de diferenças entre os grupos experimentais. O índice de significância considerado neste trabalho foi de 5%. Para ambas as técnicas de avaliação da viabilidade celular (Alamar Blue e Live/dead assay) analisadas neste trabalho, o POH foi capaz de reduzir a viabilidade celular de linhagens do CEO de língua de maneira dosedependente e tempo-dependente (p<0,05). As concentrações de 1,5 mM e 3 mM do POH obtiveram resultados melhores ou semelhantes aos encontrados na cisplatina 40 µM, para as duas linhagens, na avaliação da viabilidade celular (p<0,05). Os valores de IC50 do POH foram de 1,5 mM para a célula SCC-25 em todos os intervalos de tempo (24 h, 48 h e 72 h), uma vez que, para a linhagem HSC-3, foram de 3 mM para os tempos de 24 h e 48 h e de 1,5 mM para o intervalo de 72 h. O POH foi capaz de inibir a migração das duas linhagens celulares de CEO de maneira dependente da concentração (p≤0,05), comparados ao grupo controle. A habilidade da molécula POH se ligar a proteínas responsáveis pela ativação do ciclo celular foi avaliada usando docking models. Dentre elas, a proteína GTPase Kras mostrou a melhor energia de ligação (-86.70 kcal/mol), apresentando ligações de hidrogênio com os resíduos THR58 (A) e ASP57 (A) e ligações estéricas com os resíduos TRY32 (A) e ALA18 (A). As evidências deste estudo corroboram a ideia de que o POH possui atividade sobre o CEO, sugerindo que essa molécula possa ser uma forte candidata para o desenvolvimento de medicamentos direcionados ao tratamento desta patologia (AU).

Oral squamous cell carcinoma (OSCC) is the most frequent malignant neoplasm of the oral cavity and constitutes a public health problem due to its high incidence and mortality rate caused in many cases by therapeutic failure and tumor resistance. Therefore, the search for new biologically active molecules stands out, such as those found in products of natural origin. This work aims to evaluate the antineoplastic activity of S-(-)-perillyl alcohol (POH) in cell cultures of tongue CEO and to predict its affinity through a computer model on proteins that regulate the cell cycle. For this purpose, two cell lines of tongue CEO were used, HSC-3 and SCC-25. The following groups were analyzed: G0 (control; cells cultured in the absence of POH), G1 (cells treated with 40 µM cisplatin), G2 (cells treated with 0.5 mM POH), G3 (cells treated with 1 .0 mM), G4 (cells treated with 1.5 mM POH) and G5 (cells treated with 3.0 mM POH). Differences between these groups were investigated through the following assays: cell viability (Alamar Blue and Live/Dead assay) and migratory activity (Wound healing). Affinity prediction between POH and cell cycle control molecules were also performed using molecular docking using Molegro Virtual Docker, v. 6.0.1. The data was statistically treated by GraphPad Prism 6.0 (GraphPad Software, USA), parametric analysis using Anova test, Tukey post-test and Kruskal-Wallis non-parametric statistical test, followed by t student test were adopted for determination of differences between the experimental groups. The significance index considered in this work was 5%. For both cell viability assessment techniques (Alamar Blue and Live/dead assay) analyzed in this work, POH was able to reduce the cell viability of tongue CEO lines in a dose-dependent and time-dependent manner (p<0 .05). The concentrations of 1.5 mM and 3 mM of POH obtained better or similar results to those found in 40 µM cisplatin, for the two strains, in the evaluation of cell viability (p<0.05). The IC50 values of POH were 1.5 mM for the SCC-25 cell at all time intervals (24 h, 48 h and 72 h), since for the HSC-3 line they were 3 mM for 24 h and 48 h times and 1.5 mM for the 72 h interval. POH was able to inhibit the migration of the two DSC cell lines in a concentration-dependent manner (p≤0.05), compared to the control group. The ability of the POH molecule to bind to proteins responsible for cell cycle activation was evaluated using docking models. Among them, the protein GTPase Kras showed the best binding energy (-86.70 kcal/mol), featuring hydrogen bonds with residues THR58 (A) and ASP57 (A) and steric bonds with residues TRY32 (A) and ALA18 ( THE). The evidence from this study supports the idea that POH has antineoplastic activity on the CEO, suggesting that this molecule may be a strong candidate for the development of drugs aimed at the treatment of this pathology (AU).

Oral ID® as an adjunctive tool for surgical margin assessment in patients with oral squamous cell carcinoma: a comparative study / Oral ID® como uma ferramenta adjuvante para avaliação da margem cirúrgica em pacientes com carcinoma oral de células escamosas: um estudo comparativo

Objective: The condition of the resected margin in oral squamous cell carcinoma continues to be an important prognostic factor; the use of optic technology could help surgeons in determining the margin status at real time. This study aims to evaluate Oral ID, a hand held device that uses the principal of auto-fluorescence to determine surgical safe margins in patients with oral squamous cell carcinoma, and to compare the results with those of the conventional 1 cm margin method. Material and Methods: This study was a descriptive, comparative analytical study carried out at Khartoum Dental Teaching Hospital and Oral Histopathology Diagnostic Laboratory, Faculty of Dentistry, University of Khartoum. A total of 92 margins obtained from 31 patients, 46 margins were taken by Oral ID and the other 46 were taken by the traditional 1cm method. All margins were examined histologically with conventional Hematoxylin and Eosin stain. Results: It was found that all tumors showed fluorescence loss; A significant association was found between the use of Oral ID and obtaining a free margin P (0.02) the sensitivity of Oral ID was found to be 74% the specificity was found to be 89%. Ten out of the 46 margins obtained by fluorescence showed mild dysplasia and two margins showed high grade dysplasia. The 46 margins obtained by the traditional 1cm margin showed different field alterations two were involved, one was close, five showed high grade dysplasia and 14 showed mild dysplasia yielding a specificity of 52.2%. Conclusion: Using Oral ID for surgical margin assessment increases the accuracy to 74% compared to the conventional method which was found to be 52.2%. The results of the device are comparable to other auto-fluorescence devices of different trademarks. Further development of the device to help overcome its limitations is strongly advised (AU)

Objetivo: A condição da margem ressecada no carcinoma oral de células escamosas continua sendo um importante fator prognóstico; o uso de tecnologia óptica pode ajudar cirurgiões a determinar o status da margem em tempo real. O objetivo deste estudo é avaliar o Oral ID, um aparelho portátil que utiliza o princípio da autofluorescência para determinar margens de segurança cirúrgicas em pacientes com carcinoma oral de células escamosas, e comparar os resultados com o método convencional de margem de 1 cm. Material e Métodos: Este estudo foi um estudo descritivo, analítico e comparativo realizado no Khartoum Dental Teaching Hospital e no Laboratório de Diagnóstico de Histopatologia Oral da Faculdade de Odontologia, Universidade de Khartoum. Um total de 92 margens foram obtidas de 31 pacientes, 46 margens foram obtidas por Oral ID e as outras 46 foram obtidas pelo método tradicional de 1 cm. Todas as margens foram examinadas histologicamente com coloração convencional de Hematoxilina e Eosina. Resultados: Verificou-se que todos os tumores apresentaram perda de fluorescência; uma associação significativa foi encontrada entre o uso de Oral ID e a obtenção de uma margem livre P (0,02), a sensibilidade de Oral ID foi de 74% e a especificidade de 89%. Dez das 46 margens obtidas por fluorescência mostraram displasia leve e duas margens mostraram displasia de alto grau. As 46 margens obtidas pela margem tradicional de 1cm apresentaram diferentes alterações de campo, duas estavam envolvidas, uma estava próxima, cinco apresentaram displasia de alto grau e 14 apresentaram displasia leve com especificidade de 52,2%. Conclusão: O uso de Oral ID para avaliação da margem cirúrgica aumenta a acurácia para 74% em comparação com o método convencional, que foi encontrado em 52,2%. Os resultados do dispositivo são comparáveis a outros dispositivos de autofluorescência de diferentes marcas comerciais. O desenvolvimento do dispositivo para ajudar a superar suas limitações é fortemente recomendado. (AU)

Oral Squamous Cell Carcinoma Associated with Arsenic Exposure: A Case Series from Argentina / Carcinoma Oral de Células Escamosas Asociado con la Exposición al Arsénico: Una Serie de Casos de Argentina

ABSTRACT: Many areas of South America are directly affected by Arsenic (As) contaminated groundwater. A high percentage of the water samples taken in multiple areas of Argentina had As concentrations above the WHO level recommended guidelines. This condition was previously associated with an increased risk of chronic diseases, including different cancers. Long-term As exposure was proposed as a risk factor for Oral Squamous Cell Carcinoma (OSCC). The aim of this study is to present a series cases of Argentine patients diagnosed with OSCC who have consumed water contaminated with As for more than 10 years. Clinical data were obtained from the archive of Clinical Records Histories of the Oral Medicine Department of the Dentistry School, Universidad Nacional de Córdoba and Universidad Católica de Córdoba, Argentina. 15 cases of OSCC were included. The male: female sex ratio was 2:1. The average age was 66 years (31-89 years). Regarding location, the gum or edentulous alveolar ridge was the most prevalent site (6/15; 40 %), followed by the tongue margin. The average years of exposure to arsenical waters were 24 years (13 - 40 years of exposure). The majority of the presented cases were non drinkers non smokers. 60 % of the tumors were diagnosed at advanced stages. the epidemiological studies carried out in As-contaminated areas that address oral cancer should always incorporate the record of variables related to As exposure. Patients who live or lived at As-contaminated areas must be regularly followed up for early diagnosis of potentially malignant or malignant lesions. The high frequency of gum cancer among these cases, should raise awareness of periodontic specialists to perform a careful and thorough periodontal examination.

RESUMEN: Muchas regiones de América del Sur están directamente afectadas por aguas subterráneas contaminadas con arsénico (As). Un alto porcentaje de las muestras de agua tomadas en múltiples áreas de Argentina tenían concentraciones de As superiores al nivel aprobado por la OMS. Esta condición se asociaba previamente con un mayor riesgo de enfermedades crónicas, incluidos diferentes tipos de cáncer. La exposición a largo plazo se propuso como un factor de riesgo para el carcinoma oral de células escamosas (OSCC). El objetivo de este estudio es presentar una serie de casos de pacientes diagnosticados con OSCC que han consumido agua contaminada con As durante más de 10 años. Se obtuvieron datos clínicos del archivo de Historias de registros clínicos del Departamento de Medicina Oral de la Facultad de Odontología, Universidad Nacional de Córdoba y Universidad Católica de Córdoba, Argentina. Se incluyeron 15 casos de OSCC. La relación de género masculino: femenino fue de 2: 1. La edad promedio fue de 66 años (31-89 años). En cuanto a la ubicación, la encía o la cresta alveolar edéntula fue el sitio más frecuente (6/15; 40 %), seguido del borde de la lengua. El promedio de años de exposición a las aguas arsenicales fue de 24 años (13 - 40 años de exposición). La mayoría de los casos presentados fueron de pacientes no bebedores y no fumadores. El 60 % de los tumores fueron diagnosticados en etapas avanzadas. Los estudios epidemiológicos realizados en áreas contaminadas con As que abordan el cáncer oral siempre deben incorporar el registro de variables relacionadas con la exposición a As. Se debe hacer un seguimiento continuo de los pacientes que viven o que vivieron en áreas contaminadas con As para el diagnóstico temprano de lesiones potencialmente malignas. La alta frecuencia de cáncer de encías en estos casos, debe concienciar a los especialistas en periodoncia para que realicen un examen periodontal cuidadoso y completo.

Sociodemographic and clinicopathological profile of 80 cases of oral squamous cell carcinoma / Perfil sociodemográfico e clinicopatológico de 80 casos de carcinoma de células escamosas de boca

ABSTRACT Objective: To describe demographic and clinicopathologic profile of oral squamous cell carcinoma (OSCC) cases from incisional biopsies collected at the Nova Friburgo Health Institute of the Fluminense Federal University [Instituto de Saúde de Nova Friburgo da Universidade Federal Fluminense (ISNF/UFF)] and at the Raul Sertã Municipal Hospital [Hospital Municipal Raul Sertã (HMRS)]. Methods: Oral Pathology Laboratory records from the ISNF/UFF were reviewed and all cases of OSCC were primarily selected. Cases from ISNF/UFF and HMRS were selected and had their demographic data collected from the medical records. Clinical characteristics were evaluated using the images of the lesions taken on the biopsy day and the laboratory files. The histological slides were later reviewed. Results: Eighty cases of OSCC were identified. Most patients were male (56.7%), with a mean age of 60 years, smoker (62.71%) and/or alcoholic (44.55%). The most affected anatomic site was the tongue (39.49%), presenting mainly as an ulcer (39.49%). Microscopically, the well-differentiated lesions were more common (35.44%), and the mean counting of mitoses was 5.5/10 high-power field. Conclusion: The profile of OSCC patients in Nova Friburgo partly reflects the world literature, with emphasis on the following differences: low average number of mitoses found in the histopathological analysis and prevalence of well-differentiated lesions. Such differences may be a result of the characteristic variations of the local population, reinforcing the importance of conducting epidemiological studies that demonstrate OSCC peculiarities in different regions.

RESUMEN Objetivo: Trazar el perfil sociodemográfico y clínico de los casos de biopsia incisional de carcinoma oral de células escamosas (COCE) recogidos en el Instituto de Saúde de Nova Friburgo de la Universidade Federal Fluminense (ISNF/UFF) y en el Hospital Municipal Raul Sertã (HMRS). Métodos: Se revisaron los archivos del Laboratorio de Patología Oral, y todos los casos de COCE han sido primariamente seleccionados. Los casos procedentes del ISNF/UFF y del HMRS han sido seleccionados y sus datos demográficos han sido recogidos a partir de los historiales médicos. Las características clínicas fueron evaluadas basándose en las fotografías de las lesiones sacadas en el día de la biopsia y en las informaciones descriptas en las boletas de solicitud del laboratorio. Los portaobjetos histopatológicos fueron posteriormente revisadas. Resultados: Ochenta casos de COCE fueron identificados. La mayoría de los pacientes era del sexo masculino (56,7%), con edad media de 60 años, fumadores (62,71%) y/o alcohólicos (44,55%). La localización anatómica más afectada fue la lengua (39,49%), presentándose, principalmente, como una úlcera (39,49%). Microscópicamente, las lesiones bien diferenciadas fueron las más comunes (35,44%), y la media de mitosis cuantificada fue de 5,5/10 campos de aumento mayor. Conclusión: El perfil de los pacientes con COCE em Nova Friburgo refleja, parcialmente, la literatura mundial, destacando las siguientes diferencias: bajo número medio de mitosis encontradas en el análisis histopatológico y prevalencia de lesiones bien diferenciadas. Dichas diferencias pueden ser resultado de variaciones características de la población local, reforzando la importancia de la realización de estudios epidemiológicos que evidencien las particularidades de COCE en diferentes regiones.

RESUMO Objetivo: Traçar o perfil sociodemográfico e clinicopatológico dos casos de biópsia incisional de carcinoma de células escamosas bucal (CCEB) coletados no Instituto de Saúde de Nova Friburgo da Universidade Federal Fluminense (ISNF/UFF) e no Hospital Municipal Raul Sertã (HMRS). Métodos: Os arquivos do Laboratório de Patologia Oral foram revisados, e todos os casos de CCEB foram primariamente selecionados. Os casos oriundos do ISNF/UFF e do HMRS foram selecionados e tiveram seus dados demográficos coletados a partir dos prontuários. As características clínicas foram avaliadas com base nas fotografias das lesões tiradas no dia da biópsia e nas informações descritas nas fichas de requisição laboratorial. As lâminas histopatológicas foram revisadas posteriormente. Resultados: Oitenta casos de CCEB foram identificados. A maioria dos pacientes era do sexo masculino (56,7%), com idade média de 60 anos, tabagista (62,71%) e/ou etilista (44,55%). A localização anatômica mais acometida foi a língua (39,49%), apresentando-se, principalmente, como uma úlcera (39,49%). Microscopicamente, as lesões bem diferenciadas foram as mais comuns (35,44%), e a média de mitoses quantificada foi de 5,5/10 campos de grande aumento. Conclusão: O perfil dos pacientes com CCEB em Nova Friburgo reflete, em parte, a literatura mundial, com destaque para as seguintes diferenças: baixo número médio de mitoses encontradas na análise histopatológica e prevalência de lesões bem diferenciadas. Tais diferenças podem ser resultado das variações características da população local, reforçando a importância da realização de estudos epidemiológicos que evidenciem as particularidades de CCEB em diferentes regiões.

Perfil clínico-demográfico de los carcinomas de células escamosas bucales en una población del nordeste de Brasil / Clinical and demographic profile of oral squamous cell carcinoma in a northeast population of Brazil

Objetivo: Describir el perfil clínico-demográfico e identificar los factores de riesgo presentes en individuos portadores de carcinoma oral de células escamosas, que asistieron a un centro de referencia del nordeste de Brasil, de 2007 a 2015. Materiales y métodos: En este estudio descriptivo y retrospectivo, los datos fueron recopilados de las historias clínicas de individuos con diagnóstico histológico de carcinoma oral de células escamosas. Resultados: De los 104 casos analizados, el 72,12% eran hombres; el 53,84%, mayores de 60 años, y el 38,9%, de tez morena. La mayoría de los individuos eran alcohólicos y/o fumadores (95%). En cuanto a las lesiones, en su mayoría eran: ulceradas (58,70%), rojas (47,42%), de superficie arrugada (92,39%), duras (78,02%), con crecimiento endofítico (56,12%) y estaban localizadas en el borde lateral de la lengua (27,62%). Conclusiones: En este estudio, el carcinoma oral de células escamosas fue diagnosticado principalmente en hombres de tez morena, mayores de 60 años. Las lesiones más frecuentes fueron úlceras en la lengua. El consumo de tabaco y alcohol fueron las características de comportamiento de mayor ocurrencia (AU)

Aim: Describe the clinical-demographic profile and identify risk factors present in individuals with oral squamous cell carcinoma, attending a reference center in Northeastern Brazil from 2007 to 2015. Materials and methods: The present descriptive and retrospective study evaluated data collected from the dental records of individuals with histological diagnosis of oral squamous cell carcinoma. Results: Of the 104 cases analyzed, 72.12% were men, 53.84% were over 60 years old and 38.9% were of brown complexion. Most of the individuals were alcoholics and/or smokers (95%). The clinical characteristics were: ulcerated (58.70%), red (47.42%), rough (92.39%), hard consistency (78.02%), endophytic growth (56.12%) and located in the lateral of the tongue (27.62%). Conclusions: In this study, the oral squamous cell carcinoma was diagnosed mainly in men, brown and over 60 years. In the majority of cases, the lesions presented as ulcers in the tongue. Tobacco and alcohol consumption were the most frequent behavioral characteristics (AU)

Prevalence of methicillin resistant staphylococcus aureus isolated from saliva samples of patients with oral squamous cell carcinoma / revalencia de Staphylococcus aureus resistente a la meticilina en muestras de saliva de pacientes con carcinoma oral de células escamosas

Objectives: To study the prevalence of methicillin resistant Staphylococcus aureus (MRSA) in saliva samples of pre-surgical oral squamous cell carcinoma (OSCC) patients along with their resistance pattern to other antibiotics. Methods: Saliva samples of OSCC patients were collected and processed for isolation of MRSA. Staphylococcus aureus isolates were primarily identified using standard microbiological methods like biochemical assays, specialized media and latex agglutination test. Confirmation of MRSA strains was done by growing the isolates on MRSA agar and by using PCR to amplify two MRSA specific genes. All the isolated Staphylococcus aureus strains were subjected to antibiotic sensitivity tests. Results: A total of 17 Staphylococcus aureus strains were isolated from 50 saliva samples of pre-surgical OSCC patients of which 13 were confirmed to be MRSA. These MRSA strains were also found to be mostly resistant to other commonly used antibiotics. Univariate analysis revealed that most patients with MRSA infections had a prior history of hospitalization and surgery. Also, it was confirmed that patients with other comorbidities and infections were more prone to having MRSA present in the saliva. Conclusion: The majority of Staphylococcus aureus isolates from the saliva of OSCC patients were MRSA, and were resistant to several other commonly used antibiotics.

Objetivos: Estudiar la prevalencia de Staphylococcus aureus resistente a la meticilina (MRSA) en muestras de saliva prequirúrgicas de pacientes con carcinoma oral de células escamosas (COCE) junto con su patrón de resistencia a otros antibióticos. Métodos: Se recolectaron muestras de saliva de pacientes con COCE y se procesaron para el aislamiento de SARM. Los aislamientos de Staphylococcus aureus se identificaron principalmente mediante métodos microbiológicos estándar, como los análisis bioquímicos, los medios especializados y la prueba de aglutinación con látex. La confirmación de las cepas de SARM se realizó cultivando los aislados en agar SARM y utilizando PCR para amplificar dos genes específicos de SARM. Todas las cepas aisladas de Staphylococcus aureus se sometieron a pruebas de sensibilidad a los antibióticos. Resultados: Se aislaron un total de 17 cepas de Staphylococcus aureus a partir de 50 muestras de saliva de pacientes prequirúrgicos con COCE, de los cuales solo se confirmó que 13 eran SARM. También se encontró que estas cepas de SARM son resistentes a otros antibióticos de uso común. El análisis univariado reveló que la mayoría de los pacientes con infecciones por SARM tenían antecedentes previos de hospitalización y cirugía. Además, se confirmó que los pacientes con otras comorbilidades e infecciones eran más propensos a las infecciones por SARM. Conclusión: la mayoría de los aislamientos de Staphylococcus aureusde la saliva de los pacientes con OSCC fueron MRSA y fueron resistentes a varios otros antibióticos de uso común.

Carcinoma oral de células escamosas diagnosticado precozmente: Reporte de caso y revisión de literatura

l carcinoma oral de células escamosas (COCE) es la neoplasia maligna más común de origen epitelial en la cavidad bucal, suele afectar en su mayoría a hombres mayores de 40 años de edad. Los sitios de localización más frecuentes son la lengua y el piso de la boca. La etiología es multifactorial siendo el tabaco y el alcohol los factores de riesgo más importantes. La presentación clínica es variable y aunque es precedido por cambios visibles en la mucosa oral el diagnóstico suele realizarse de forma tardía. Un diagnóstico precoz es de importancia crítica para mejorar la sobrevida y los resultados del tratamiento. El tamizaje del cáncer bucal es efectivo al reducir la mortalidad y morbilidad de cáncer bucal. El objetivo de este trabajo es presentar un caso de COCE y evidenciar la importancia de un diagnóstico precoz utilizando el tamizaje de cáncer bucal, así como la revisión de literatura en cuanto a esta patología.

ral squamous cell carcinoma (OSCC) is the most common malignant neoplasm of epithelial origin in the oral cavity, usually affecting men over 40 years of age. The most frequent localization sites are the tongue and the floor of the mouth. The etiology is multifactorial being tobacco and alcohol the most important risk factors. The clinical presentation is variable and although it is preceded by visible changes in the oral mucosa, the diagnosis is usually made late. An early diagnosis is critically important to improve survival and treatment outcomes. Oral cancer screening is effective in reducing the mortality and morbidity of oral cancer. The purpose of this study was to present a case of OSCC and to highlight the importance of an early diagnosis using oral cancer screening, and the review of the relevant literature as for this pathology.

Correlación histológica de expresión de marcadores Ki-67 y ciclina D1 presentes en carcinomas de células escamosas en cavidad oral / Histological correlation of Ki-67 and D1 cycline markers expression in squamous cell carcinoma in the oral cavity

Resumen: Introducción: El carcinoma oral de células escamosas (COCE) es una neoplasia maligna originada en los queratinocitos del epitelio. Biopsias tempranas, evidencian queratinocitos mitóticos displásicos e infiltrados inflamatorios subepiteliales que progresan a pérdida de la membrana basal. Sin embargo, en el diagnóstico histológico con hematoxilina y eosina (H&E) no se muestra adecuada correlación clínica, aspecto que mejora cuando se utilizan marcadores moleculares como Ki-67 y ciclina D1. El objetivo de este estudio es correlacionar la descripción histológica de casos de COCE con la expresión de Ki-67 y ciclina D1. Material y métodos: Se analizaron 12 pacientes con lesiones sugestivas de cáncer oral; fueron incluidos en el estudio pacientes con diagnóstico de COCE. Se tomaron biopsias únicas, procesamiento histotécnico para cortes en parafina, coloración con H&E y coloración inmunohistoquímica con ciclina D1 y Ki-67. Tres pacientes cumplieron con los criterios de inclusión, llamados C1, C2 y C3. Se clasificó el tipo de COCE según el American Joint Committee on Cancer. Resultados: Histológicamente el caso C1 fue clasificado como COCE tipo II, los casos C2 y C3 tipo I; en la inmunohistoquímica encontramos en C1 Ki-67 positivo y ciclina D1 negativo, para C2, Ki 67 negativo y ciclina D1 positivo y para C3 Ki-67 positivo y ciclina D1 negativo. Conclusiones: La búsqueda de marcadores como Ki67 y ciclina D1 en diagnósticos de COCE preestablecidos, pueden influenciar los resultados histológicos, contribuyendo a un diagnóstico más acertado así como los tratamientos a realizar en el paciente.

Abstract: Introduction: Oral squamous cell carcinoma (OSCC) is a malignant neoplasia originated in the epithelium's keratocytes. Early biopsies reveal dysplastic mitotic keratocytes and sub-epithelial inflammatory infiltrate which progress towards a loss of basal membrane. Nevertheless, hematoxillin and eosin (H&E) histological diagnosis does not show suitable clinical correlation; this aspect improves when molecular markers such as Ki-67 and cyclin D1 are used. The aim of the present study was to correlate histological description of OSCC cases with Ki-676 and cyclin D1 expression. Material and methods: Twelve patients with lesions suggestive of oral cancer were analyzed, patients with OSCC diagnosis were included in the study. Single biopsies were taken, observing histological and technical processing for paraffin cuts, coloration with H&E and immunohistochemical coloration with cyclin D1 and Ki-67. Three patients met inclusion criteria, they were named C1, C2 and C3. OSCC type was classified according to the American Joint Committee on Cancer. Results: Histologically, C1 case was classified as type II OSCC. Cases C2 and C3 were classified as type I OSCC. Immunohistochemical analysis for C1 revealed Ki-67 positive and cyclin D1 negative; C2 exhibited Ki-67 negative and cyclin D1 positive, and C3 showed Ki-67 positive and cyclin D1 negative. Conclusions: Search for markers such as Ki67 and cyclin D1 in pre-established OSCC diagnoses can influence histological results, contributing thus to more accurate diagnosis and treatment for the patients.

Análisis histopatológico de casos de cáncer oral en instituciones de las regiones chilenas del Maule y Bío-Bío entre los años 2001-2011 / Histopathological analysis of oral cancer cases in health institutions of Maule and Bío-Bío Chilean regions between the years 2001-2011

El carcinoma oral de células escamosas (COCE) es una neoplasia epitelial invasiva con diferentes grados de diferenciación y una propensión a metástasis. La evidencia acumulada para el COCE en Chile es escasa, y más aún para la séptima región del Maule y octava región del Bío-Bío, por lo tanto el motivo de esta investigación es presentar un análisis histopatológico de pacientes diagnosticados de COCE que aporte al conocimiento de la realidad local y nacional. Se realizó un estudio observacional retrospectivo, que incluyó a una muestra por conveniencia (COCE n = 33) de instituciones de la séptima y octava región de Chile. La edad media de los pacientes fue de 65 años. La ubicación anatómica más frecuente para el COCE fueron los labios (36,4 por ciento), seguido de la lengua (27,3 por ciento) y el piso de la boca (9,1 por ciento). Predominaron los COCE moderadamente diferenciados (51,5 por ciento), con un patrón de invasión tumoral infiltrante (81,8 por ciento) y una respuesta inmune moderada/marcada (75,8 por ciento). En estas regiones el COCE afecta principalmente a personas mayores, se ubica en una zona anatómica fácilmente accesible para el examen, lo que debería permitir el diagnóstico en etapas iniciales. Son necesarios profesionales con conocimientos de posgrado o especialización en patología y medicina oral en los centros de atención pública.

Squamous cell carcinoma of the oral cavity (OSCC) is an invasive epithelial neoplasm with varying degrees of differentiation and propensity to metastasise. Chilean evidence for OSCC is scarce, and even more so for the Seventh (Maule) and Eighth (Bío-Bío) regions. Hence, the present study is carried out to evaluate the histopathological features of OSCC patients to contribute to local and national knowledge. A retrospective observational study was conducted on a convenience sample (n = 33) from health care institutions of Seventh and Eighth Chilean regions. The mean age of patients was 65 years. The most common OSCC anatomical locations were lips (36.4 percent), followed by the tongue (27.3 percent), and the floor of the mouth (9.1 percent). Moderately differentiated OSCC predominated (51.5 percent), with a pattern of infiltrating tumour invasion (81.8 percent) and a moderate/strong immune response (75.8 percent). In these Chilean regions, OSCC mainly affects older people and is located in an easily accessible area for anatomical examination, which should allow early diagnosis. Professionals with post-graduate knowledge or expertise in Pathology and Oral Medicine are needed in public health care centres.

Assessment of Tumor Associated Tissue Eosinophilia (TATE) in Oral Squamous Cell Carcinoma Using Carbol Chromotrope Stain / Evaluación de la Eosinofilia Tisular Asociada al Tumor (TATE) en el Carcinoma Oral de Células Escamosas Mediante la Tinción de Carbol Cromótropo

Tumor related tissue eosinophilia (TATE) is a known phenomenon but its role in prognostics and correlation with size of the primary tumor is still controversial. Using a stain, like Carbol chromotrope, that targets eosinophils exclusively and vividly, offers an advantage over haematoxylin and eosin, which was used in most of the studies. Forty-nine cases of oral squamous cell carcinoma, where the TNM staging has been recorded in their history, was taken and stained with Lendrum's carbol chromotrope. Significant difference in the eosinophil count with varying size of the tumor and a parallel increase in the number noted, with increase in size. There is a corresponding increase in the number of eosinophils infiltrating the tumor with increase in size of oral squamous cell carcinoma.

La eosinofilia tisular asociada a tumores (TATE) es un fenómeno conocido, sin embargo su pronóstico y correlación con el tamaño del tumor primario aún es tema de controversia. El uso de cromotropo como tinción dirigida exclusivamente a los eosinófilos, ofrece una ventaja sobre la hematoxilina-eosina, que ha sido utilizada en la mayoría de los estudios. Se estudiaron células escamosas en 49 casos de carcinoma oral, con registro del estadio TNM. Las células fueron teñidas con carbol cromotropo de Lendrum. Se observó una diferencia significativa en el recuento de eosinófilos con el tamaño del tumor y un aumento paralelo en número, con el aumento de tamaño. Hay un aumento correspondiente en el número de eosinófilos que infiltran el tumor con aumento en el tamaño de carcinoma de células escamosas orales.

Immunoexpression of p53 in Oral Squamous Cell Carcinoma and Oral Dysplastic Lesions in Patients with the Habit of Reverse Smoke / Inmunoexpresión de p53 en Carcinoma Bucal Escamo Celular y Displasias Orales en pacientes con el Hábito de Fumar Invertido

Molecular biological markers have been suggested to be of value in the diagnosis and prognostic evaluation of precancerous lesions. The purpose of the current study was to investigate the expression of p53 protein in normal oral mucosa, oral dysplastic lesions (DL), and oral squamous cell carcinoma (SCC), comparing patients with the habit of reverse smoking and conventional smokers. The patients were subjected to incisional biopsy and the soft tissue specimens were routinely fixed in 10% formalin and processed in the laboratory. Immunohistochemical technique was performed using the avidin-biotin-peroxidase protocol. The 102 patients included 42 reverse smokers and 60 conventional smokers. There were 79 cases of mild, 15 of moderate, and 3 of severe epithelial dysplasia. Five microinvasive oral SCC included one male and four females. The clinical characteristics of microinvasive tumors included patches, plaques or erosions; 100% showed positive nuclear staining for p53. It was found a significant association of p53 expression and exposure of reverse smoking among microinvasive oral SCC and oral DL patients in the population studied.

Marcadores biológicos moleculares se han sugerido para ser de valor en el diagnóstico y evaluación pronóstica de lesiones precancerosas. El propósito del presente estudio fue investigar la expresión de la proteína p53 en mucosa oral normal, lesiones displásicas orales (LD), y en el carcinoma oral de células escamosas (COCC), comparando pacientes con el hábito de fumar convencional y fumar invertido. Los pacientes fueron sometidos a biopsia por incisión y los especímenes de tejidos blandos fueron fijados en formalina al 10% y se procesaron en el laboratorio. La técnica inmunohistoquímica se realizó utilizando el protocolo de avidina-biotina-peroxidasa. De los 102 pacientes incluidos, 42 fueron fumadores invertidos y 60 fumadores convencionales. Hubo 79 casos de displasia epitelial leve, 15 moderada, y 3 severa. Cinco casos de COCC microinvasivo incluyeron un hombre y cuatro mujeres. Las características clínicas de los tumores microinvasores incluyen parches, placas o erosiones; el 100% mostró tinción nuclear positiva para p53. Se encontró una asociación significativa de la expresión de p53 y la exposición de los fumadores invertidos entre pacientes con COCC microinvasivo y DL en la población estudiada.

4NQO carcinogenesis: a model of oral squamous cell carcinoma / Carcinogenesis inducida por 4NQO: un modelo de carcinoma oral de células escamosas

The experimental oral carcinogenesis induced by the chemical 4-nitroquinoline 1-oxide (4NQO) is one of the most frequent in the study of squamous cell carcinoma of the oral cavity (CCEC). The clear advantage is that the model is very similar to the physiological process of malignancy. The model has clear benefits by and is suitable for applications in therapeutic research.

La carcinogénesis oral experimental inducida por el químico 4-nitroquinolina 1-óxido (4NQO) es uno de los métodos más frecuentes en el estudio del carcinoma de células escamosas de la cavidad oral (CCECO). La clara ventaja del modelo radica en el gran parecido al proceso fisiológico de la neoplasia maligna. El modelo tiene beneficios claros y es adecuado para las aplicaciones de la investigación terapéutica.

Serum albumin in poorly differentiated, oral squamous cell carcinoma: a possible diagnostic marker of significance / Albumina sérica em carcinomas de células orais escamosas e pobremente diferenciadas: um possível marcador de diagnóstico de significância

Objectives: Serum albumin is considered to be the most potent and abundant extra-cellular anti-oxidant thatmight have a protective role in the ongoing process of transition of the various oral pre-cancerous lesions andconditions into frank malignant degenerations. The aim of this study was to check the reliability of serum albuminas one of the diagnostic anti-oxidant parameter. Materials and methods: The study consisted of seraanalysis of albumin in the age and sex matched normal healthy adults and patients with histologically proven,poorly differentiated oral squamous cell carcinoma. The results were analyzed using Student’s t-test andwere averaged as mean ± standard deviation. In above test, p-values less than 0.05 were taken to be statisticallysignificant. The normality of data was checked before the statistical analysis was performed. Results:The study revealed variations in sera levels of albumin to be statistically significant with the mean level ofsera albumin to be 4.956 ± 1.0579 in controls as against 3.6933 ± 1.2177 in patients with histologically proven,poorly differentiated, oral squamous cell carcinoma. Conclusions: The results of the study emphasize theneed for more studies with larger sample sizes to be conducted before a conclusive role could be drawn infavor of sera levels of albumin as diagnostic markers of significance in oral squamous cell carcinoma.

Objetivos: A albumina sérica é considerada o antioxidante extracelular mais poderoso e mais abundante, que pode exercer um papel protetor no processo de transição das várias lesões e circunstâncias pré-cancerígenasorais em degenerações malignas. O objetivo deste estudo foi verificar a confiabilidade da albumina sérica como um dos parâmetros de diagnóstico antioxidante. Materiais e métodos: A análise consistiu no estudo da albumina sérica em pacientes adultos saudáveis normais, separados por idade e sexo, e em pacientes com carcinoma oral de células escamosas pobremente diferenciadas com evidência histológica comprovada. Os resultados foram analisados usando o teste t de Student, e as médias foram calculadas com ± desvio-padrão. No teste citado, os valores de p menores que 0,05 foram considerados estatisticamente significantes. A normalidade dos dados foi verificada antes da realização da análise estatística. Resultados: O estudo revelou diferenças estatisticamente significantes nos níveis de albumina sérica com o nível médio de 4.956 ± 1.0579 nos controle sem contraste com 3.6933 ± 1.2177 nos pacientes com carcinoma oral de células escamosas pobremente diferenciadas.Conclusões: Os resultados do estudo enfatizaram a necessidade de mais estudos com tamanhos de amostra maiores antes que um papel conclusivo possa ser atribuído, em favor dos níveis de albumina sérica,como marcador diagnóstico para o carcinoma oral de células escamosas.