Alteration in Serum Lipid Profile Pattern in Oral Squamous Cell Carcinoma and Potentially Malignant Disorders

ABSTRACT Objective: To evaluate and compare lipid profile level in oral submucous fibrosis (OSMF), oral leukoplakia (OL) and oral squamous cell carcinoma (OSCC) patients. Material and Methods: Thirty histopathologically diagnosed subjects each of OL, OSMF, OSCC were recruited along with 30 healthy controls. 5ml of venous blood is collected and estimated using standard diagnostic kits. Results: The mean of Total cholesterol level in controls was 219.03 mg%, in OSCC, OL and OSMF was 142.89 ± 10.21mg%, 155.44 ± 17.63 mg% and 180.60 ± 13.25 mg%, respectively. The mean low-density lipid level in controls was 137.24 mg and in OSCC, OL and OSMF groups were 109.28 ± 2.16 mg%, 126.63 ± 0.85 mg% and 119.15 ± 0.93 mg%, respectively. The mean of high-density lipid level in controls, OSCC, OL and OSMF was 42.87 ± 0.42 mg%, 36.50 ± 2.31 mg%, 21.13 ± 0.77 mg% and 28.37 ± 1.11mg%, respectively. The mean of very low density lipids level in controls, OSCC, OL and OSMF was 30.12 ± 1.51 mg%, 17.24 ± 0.80 mg%, 22.25 ± 0.93 mg% and 25.89 ± 0.43 mg%, respectively. The mean triglyceride level in controls, OSCC, OL and OSMF was 118.80 ± 9.47 mg%, 91.2 ± 3.03 mg%, 105.05 ± 2.96 mg% and 106.19 ± 3.09 mg%, respectively. Conclusion: Lipid profile levels could be early indicators of precancer and cancer.

Expression profile of salivary micro RNA-21 and 31 in oral potentially malignant disorders

Abstract Oral potentially malignant disorders (OPMD) possess significant chances of malignancy conversion. In order to develop an early diagnostic tool, the present study evaluated the expression of miRNA-21 and 31 as salivary markers. The case-control study was carried out in 36 healthy participants as controls and in 36 patients who were newly diagnosed as OPMD having four different lesions including leucoplakia, oral sub mucous fibrosis (OSMF)궱, oral lichen planus, and (OSMF)궱 with leucoplakia. The samples were also classified as non-dysplastic, or with mild, moderate, and severe dysplasia according to their histopathological reports. The salivary miRNA-21 and 31 expressions were studied using real-time PCR. The statistical analysis was carried out using SPSS version 22. Salivary miRNA-21 (p-value = 0.02) and 31 (p-value = 0.01) were significantly upregulated in severe dysplasia compared with control. Among the different lesions, leucoplakia had significant upregulation of miRNA-21 and 31. miRNA-21 can be used as a diagnostic marker with specificity of 66% and sensitivity of 69%. The area under the ROC curve was 0.820 for miRNA-21 and 0.5 for miRNA-31, which proved that miRNA-21 is a better diagnostic marker than miRNA-31 for OPMD.

DEC1: a potential biomarker of malignant transformation in oral leukoplakia

Abstract The purpose of this study was to analyze the differential expression of DEC1 in oral normal mucosa (NM), oral leukoplakia (OLK) and oral squamous cell carcinoma (OSCC). Surgically excised specimens from patients with OLK (n = 47), OSCC (n = 30) and oral normal mucosa (n=11) were immunostained for DEC1. The expression of DEC1 protein was evaluated, and its association with the clinicopathological features was analyzed. The expression of DEC1 in NM, OLK and OSCC tissues increased in turn, and significant differences were observed among the groups (P < 0.0001). In terms of the association between DEC1 expression and epithelial dysplasia, DEC1 expression was lower in hyperkeratosis without dysplasia (H-OLK) than in OLK with moderate to severe dysplasia (S-OLK), and these differences were significant (p < 0.05). The expression of DEC1 in OSCC with OLK was significantly higher than that in OSCC without OLK (p < 0.01). Therefore, DEC1 could be a potential biomarker of malignant transformation in the carcinogenesis of OSCC, which may provide a new research direction for the transformation of oral potentially malignant disorders (OPMDs) into OSCC.

BMI-1 expression increases in oral leukoplakias and correlates with cell proliferation

Abstract Oral leukoplakia (OL) is a white lesion of an indeterminate risk not related to any excluded (other) known diseases or disorders that carry no increased risk for cancer. Many biological markers have been used in an attempt to predict malignant transformation; however, no reliable markers have been established so far. Objective To evaluate cell proliferation and immortalization in OL, comparing non-dysplastic (Non-dys OL) and dysplastic OL (Dys OL). Methodology This is a cross-sectional observational study. Paraffin-embedded tissue blocks of 28 specimens of Non-dys OL, 33 of Dys OL, 9 of normal oral mucosa (NOM), 17 of inflammatory hyperplasia (IH), and 19 of oral squamous cell carcinomas (OSCC) were stained for Ki-67 and BMI-1 using immunohistochemistry. Results A gradual increase in BMI-1 and K-i67 expression was found in oral carcinogenesis. The immunolabeling for those markers was higher in OSCC when compared with the other groups (Kruskal-Wallis, p<0.05). Ki-67 expression percentage was higher in OL and in IH when compared with NOM (Kruskal-Wallis/Dunn, p<0.05). Increased expression of BMI-1 was also observed in OL when compared with NOM (Kruskal-Wallis/Dunn, p<0.05). No differences were observed in expression of both markers when non-dysplastic and dysplastic leukoplakias were compared. A significant positive correlation between Ki-67 and BMI-1 was found (Spearman correlation coefficient, R=0.26, p=0.01). High-grade epithelial dysplasia was associated with malignant transformation (Chi-squared, p=0.03). Conclusions These findings indicate that BMI-1 expression increases in early oral carcinogenesis and is possibly associated with the occurrence of dysplastic changes. Furthermore, our findings indicate that both Ki-67 and BMI-1 are directly correlated and play a role in initiation and progression of OSCC.

Análise comparativa entre a coloração do azul de toluidina e a imunoexpressão da ciclina D1 em leucoplasias da mucosa bucal com diferentes graus de atipia / Comparative analysis between the coloring of toluidine blue and the immunoexpression of cyclin D1 in leucoplakias of the bucal mucosa with different degrees of atipia

O câncer de boca ocupa uma posição de destaque em relação ao número total de casos registrados no Brasil. A displasia epitelial (DE) oral é um achado histopatológico associado a um risco aumentado de transformação maligna do epitélio oral. A falha nos mecanismos de sinalização celular, no controle do ciclo celular ou nos mecanismos para reparar danos celulares pode favorecer a processos que culminam com a progressão para o câncer. Objetivo: avaliar comparativamente a resposta clínica da marcação do azul de toluidina (AT) e a imunoexpressão da proteína ciclina D1, uma proteína nuclear de grande importância como regulador da transição da fase G1 para fase S do ciclo celular, em leucoplasias oral (LO). Metodologia: avaliamos 12 pacientes que apresentavam, na cavidade bucal, lesões com diagnóstico clínico de LO. O estudo se desenvolveu em duas etapas: clínica e laboratorial. Foi feita marcação com AT e avaliação Imuno-histoquímica, respectivamente. Após análise quantitativa das lâminas, os dados obtidos foram analisados pelo programa BIOESTAT 2.0, por meio dos testes de Spearman e pelo teste de correlações múltiplas de Pearson. Resultados: não foi observada relação entre a marcação clínica do AT, o grau de displasia da lesão e a imunoexpressão da Ciclina D1 em LO. Conclusão: 82% das lesões apresentaram DE em graus variados, confirmando a necessidade de se realizar o diagnóstico histopatológico das LO e o acompanhamento clínico posterior dos pacientes.

Mouth cancer occupies a prominent position in relation to the total number of cases registered in Brazil. Oral epithelial dysplasia (ED) is a histopathological finding associated with an increased risk of malignant transformation of oral epithelium. The failure in the mechanisms of cell signaling, cell cycle control mechanisms or to repair cell damage can favor processes that culminate with the progression to cancer. Objective: evaluate comparatively the clinical response of the toluidine blue marking (TB) and immuno-expression of cyclin D1 protein, a nuclear protein of great importance as a factor regulating the transition from G1 phase to S phase of the cell cycle, in oral leukoplakia (OL). Methodology: we evaluated 12 patients who presented lesions in the oral cavity with clinical diagnosis of OL. The study was developed in two stages: Clinical and Laboratorial. Marking was made with TB and immunohistochemical evaluation, respectively. After quantitative analysis of blades, the data obtained were analyzed by BIOESTAT program 2.0 through Spearman tests and by Pearson multiple correlation test. Results: no relation was observed between clinical marking of TB, the degree of dysplasia of the lesion and the immuno-expression of Cyclin D1 in OL. Conclusion: 82% of the lesions presented DE in varying degrees, confirming the need to perform histopathological diagnosis of the OL and the subsequent clinical monitoring of the patients.

Proliferative verrucous leukoplakia: diagnosis, management and current advances / Leucoplasia verrucosa proliferativa: diagnóstico, conduta e avanços atuais

Abstract Introduction: Proliferative verrucous leukoplakia is a multifocal and progressive lesion of the oral mucosa, with unknown etiology, and commonly resistant to all therapy attempts with frequent recurrences. It is characterized by a high rate of oral squamous cell carcinoma and verrucou carcinoma transformations. Objective: To analyze the studies about Proliferative verrucous leukoplakia and develop a concise update. Methods: A Pubmed search identifying studies (laboratory research, case series and reviews of literature) that examined patients with Proliferative verrucous leukoplakia was realized. Results: There are not enough studies about Proliferative verrucous leukoplakia in the literature. The few found studies not present a consensus about its etiology and diagnosis criteria. Although several treatment strategies have been proposed, most of them still show a high recurrence rate. Conclusion: More research about Proliferative verrucous leukoplakia is necessary to understand and treat this disease.

Resumo Introdução: Leucoplasia verrucosa proliferativa (LVP) é uma lesão multifocal e progressiva da mucosa oral, com etiologia desconhecida e comumente resistente a todas as tentativas terapêuticas, com recorrências frequentes. É caracterizada por uma alta taxa de transformação em carcinoma de células escamosas e carcinoma verrucoso da cavidade oral. Objetivo: Analisar os estudos sobre LVP e elaborar uma atualização resumida. Método: Foi realizada uma pesquisa na base de dados Pubmed que identificou estudos (pesquisas laboratoriais, séries de casos e revisões de literatura) que avaliaram pacientes com LVP. Resultados e discussão: Não há estudos suficientes sobre LVP na literatura. Os poucos estudos encontrados não apresentam consenso quanto aos critérios de etiologia e diagnóstico. Embora várias estratégias de tratamento tenham sido propostas, a maioria ainda apresenta alta taxa de recorrência. Conclusão: Mais pesquisas sobre LVP são necessárias para entender e tratar essa doença.

Immunoexpression of cleaved caspase-3 shows lower apoptotic area indices in lip carcinomas than in intraoral cancer

ABSTRACT Objective This study aimed to evaluate apoptosis by assessing cleaved caspase-3 immunoexpression in hyperplastic, potentially malignant disorder (PMD), and malignant tumors in intraoral and lower lip sites. Material and Methods A retrospective study using paraffin blocks with tissues from patients with inflammatory fibrous hyperplasia (IFH), actinic cheilitis, oral leukoplakia, lower lip and intraoral squamous cell carcinoma (SCC) was performed. The tissues were evaluated by immunohistochemical analysis with anti-cleaved caspase-3 antibody. Apoptotic area index was then correlated with lesion type. Results From 120 lesions assessed, 55 (46%) were cleaved caspase-3-positive. The SCC samples (n=40) had the highest apoptotic area indices (n=35; 87.5%). Significant differences were detected between SCCs and PMDs (p=0.0003), as well as SCCs and IFHs (p=0.001), regarding caspase-3 immunopositivity. Carcinomas of the lower lip had lower apoptotic area indices than intraoral cancer (p=0.0015). Conclusions Cleaved caspase-3 immunoexpression showed differences in oral SCCs and PMDs and demonstrated a distinct role of apoptosis in carcinogenesis of intraoral and lower lip cancer. In future, the expression of cleaved caspase-3 with other target molecules in oral cancer may be helpful in delineating the prognosis and treatment of these tumors.

Potentially malignant oral lesions: clinicopathological correlations / Lesões orais potencialmente malignas: correlações clínico-patológicas

ABSTRACT Objective To determine the incidence of potentially malignant oral lesions, and evaluate and correlate their clinical and pathological aspects. Methods The sample consisted of cases clinically diagnosed as oral leukoplakia, oral erythroplakia, erythroleukoplakia, actinic cheilitis, and oral lichen planus treated at a diagnostic center, between May 2012 and July 2013. Statistical tests were conducted adopting a significance level of 5% (p≤0.05). Results Out of 340 patients, 106 (31.2%) had potentially malignant oral lesions; and 61 of these (17.9%) were submitted to biopsy. Actinic cheilitis was the most frequent lesion (37.5%) and the lower lip was the most affected site (49.6%). Among 106 patients in the sample, 48 (45.3%) reported nicotine consumption, 35 (33%) reported alcohol intake and 34 (32.1%) sun exposure while working. When clinical and histopathological diagnoses were compared, oral erythroplakia and atypical ulcer were the lesions that exhibited greater compatibility (100% each). Conclusion In most cases, clinical and histopathological diagnoses were compatible. An association between the occurrence of erythroplakia, leukoplakia and erythroleukoplakia with smoking was observed. Similarly, an association between actinic cheilitis and sun exposure was noted. Erythroleukoplakia presented the highest malignancy grade in this study. Finally, dental surgeons should draw special attention to diagnosis of potentially malignant oral lesions, choose the best management, and control the lesions to avoid their malignant transformation.

RESUMO Objetivo Verificar a incidência das lesões orais potencialmente malignas, e avaliar e correlacionar seus aspectos clínico-patológicos. Métodos A amostra foi composta pelos casos diagnosticados clinicamente como leucoplasia oral, eritroplasia oral, eritroleucoplasia, queilite actínica e líquen plano oral em um serviço de diagnóstico no período entre maio de 2012 e julho de 2013. Foram realizados testes estatísticos adotando-se nível de significância de 5% (p≤0,05). Resultados Dos 340 pacientes examinados, 106 (31,2%) se apresentaram com lesões orais potencialmente malignas; destes, 61 (17,9%) biópsias foram realizadas. A lesão mais frequente foi a queilite actínica (37,5%), e o sítio anatômico mais acometido foi o lábio inferior (49,6%). Entre os 106 pacientes da amostra, 48 (45,3%) relataram consumo de nicotina, 35 (33%) ingeriam bebidas alcoólicas e 34 (32,1%) trabalhavam expostos ao sol. Comparando o diagnóstico clínico com o histopatológico, as lesões que apresentaram maior compatibilidade foram a eritroplasia oral e a lesão ulcerada atípica (100% ambas). Conclusão Na maioria dos casos, houve compatibilidade do diagnóstico clínico com o histopatológico. Notou-se correlação entre a ocorrência de eritroplasia, leucoplasia e eritroleucoplasia com o hábito de fumar, e entre a queilite actínica com a exposição solar. A eritroleucoplasia foi a lesão que demonstrou maior grau de malignização neste estudo. Diante do exposto, recomenda-se maior atenção por parte dos cirurgiões-dentistas ao diagnóstico das lesões orais potencialmente malignas, para aplicação da melhor conduta e controle da lesão, impedindo sua transformação maligna.

Altered ß-catenin expression in oral mucosal dysplasia: a comparative study

Objective The current study aimed to investigate the β-catenin expression in oral leukoplakia (OL) with different degrees of epithelial dysplasia and normal oral mucosa.Material and Methods Formalin-fixed, paraffin-embedded tissue samples of 39 OL (mild dysplasia n=19, moderate dysplasia n=13, and severe dysplasia n=7), and 10 normal oral mucosa (control group) were submitted to immunohistochemical reactions to anti-β-catenin primary antibody. A qualitative β-catenin analysis was performed based on the percentage of positive cells. The cellular location and the epithelial layer were also considered. The Chi-square test and the Fisher’s exact test were used to verify possible differences in the β-catenin expression among the OL groups. A p-value of <0.05 was considered statistically significant.Results Membranous expression of β-catenin in parabasal and basal layers was gradually lost in the higher degrees of epithelial dysplasia. In normal oral mucosa, β-catenin was detected only in the cytoplasmic membrane. However, a significant increase in cytoplasmic β-catenin could be observed between mild and moderate dysplasia (Fisher Exact test - p<0.001) and between mild and severe dysplasia (p<0.001).Conclusions The β-catenin cytoplasmic expression observed in this study may represent the initial stage of modifications in the E-cadherin-catenin complex, along with morphological cellular changes.

Clinicopathologic assessment of Candida colonization of oral leukoplakia.

Background: Leukoplakia is the most common premalignant lesion of the oral mucosa. We studied the colonization of Candida in oral leukoplakia using direct microscopy, culture and histopathology to determine if there is a statistical correlation between Candida invasion and the clinical appearance and presence of epithelial dysplasia in leukoplakia. Methods: Samples were collected from 40 patients with oral leukoplakia and 21 controls. The swabs collected were used to inoculate Sabouraud's dextrose agar slant and for direct microscopy with Gram's stain. Culture growths were subjected to germ tube and corn meal agar tests to differentiate between Candida albicans and non-albicans groups. Biopsies were also done in all patients for histopathological confirmation; Gomori's methanamine silver stain was used to identify fungal invasion of lesional epithelium. Results and Conclusions: Nineteen cases of leukoplakia showed Candida on direct smears, compared to 3 controls. Eighteen cases and one control showed growth of Candida on culture. Non-homogenous leukoplakia showed a higher positivity rate on microscopy and culture than homogenous lesions. All these correlations were statistically significant. Forty percent of leukoplakia cases were simultaneously positive for Candida on direct microscopy, culture and histopathologic evaluation. No significant difference was found between non-dysplastic and distinctly dysplastic lesions with respect to Candida detection on microscopy or culture.

Leucoplasia pilosa bucal: presentación de caso clínico / Bucal hairy leukoplakia: a case report

Se presenta caso clínico de paciente con lesiones blanquecinas en bordes laterales de lengua de 1 año de evolución aproximadamente; clínicamente asintomático, sin hábitos tóxicos ni antecedentes médicos de importancia. Actualmente bajo tratamiento ortodóntico, en donde el especialista lo alerta sobre la importancia de interconsultar con el Patólogo Bucal. Luego de una exhaustiva historia clínica, se toma muestra de la lesión y el examen histopatológico arrojó: hiperplasia epitelial exofítica, paraqueratosis excesiva y células superficiales en forma de globo con típica fragmentación nuclear, indicativo de inclusión viral (Cuerpos de Cowdry). Con estos hallazgos, la correlación con las características clínicas de la lesión y los exámenes serológicos (positivo para VIH), se llega a un diagnóstico conclusivo de Leucoplasia Pilosa Bucal (LPB). Se remitió el paciente al Instituto Anzoatiguense de la Salud (SALUDANZ), entidad encargada de problemas de Salud Pública en el Edo. Anzoátegui. La Leucoplasia Pilosa Bucal (LPB) se presenta comúnmente en pacientes VIH+ y representa un factor informativo y predictivo para el odontólogo, estomatólogo y cualquier especialista de la rama de la salud, en cuanto al tratamiento, diagnóstico y pronóstico bucal y sistémico del paciente.

We report the clinical case of a patient with whitish lesions on lateral tongue edges with 1 year of evolution approximately, clinically asymptomatic, without toxic habits or important medical history. The patient was in orthodontic treatment, when the specialist warns the importance of Bucal Pathologist review. After a thorough medical history, biopsy was taken and histopathological examination showed: exophytic epithelial hyperplasia, excessive parakeratosis and superficial balloon cells with typical nuclear fragmentation, indicative of viral inclusion (Cowdry Body´s). With these findings and correlation with lesion clinical features and serological tests (HIV positive), the final diagnosis was Bucal Hairy leukoplakia (OHL). The patient was referred Anzoatiguense Health Institute (Saludanz), entity responsible of public health problems in the Anzoátegui State, Venezuela. The Bucal Hairy Leukoplakia (OHL) occurs commonly in HIV patients and represents an informative and predictive factor for the dentist, stomatologist and any health branch specialist for treatment, diagnosis and prognosis of the patient.

Prevalencia de lesiones benignas y desórdenes potencialmente malignos que afectan la mucosa bucal en pacientes adultos Facultad de Odontoloía UCV / Injury prevalence of benign and potencially malignant disorders affecting the mouth in patients mucosal Faculty of Dentistry UCV

Se realiza un estudio de tipo documental, retrospectivo, transversal. La población del presente estudio estuvo representada por un total de 9.000 historias diagnosticadas en el Laboratorio Central de Histopatología Bucal "Dr. Pedro Tinoco" de la Facultad de Odontología de la U.C.V., durante el período 1988-2008. La muestra evaluada quedó conformada por un total de Cuatro Mil Ciento Sesenta y Seis (4.166) casos, los cuales fueron seleccionados de manera intencional no probabilística a partir de la población antes mencionada siguiendo criterios de inclusión y exclusión. La prevalencia de Lesiones Benignas y Desórdenes Potencialmente Malignos que afectan la Mucosa Bucal es alta (46,2%) con respecto a la muestra total estudiada (9000 casos). De acuerdo al Grupo Etario observamos un intervalo de edad entre 15 y 97 años, una media de 47,3 años y Desv. Tip de 16,5 (Y ± s : 47,3 ± 16,5). En relación a la distribución por Género, en nuestro estudio existe un predominio de las lesiones de la mucosa bucal por el sexo femenino (69,7%). En base al diagnóstico clínico se identificaron 77 lesiones diferentes. El Fibroma Traumático fue la lesión más común con 1042 casos (25,01%), seguida por la Leucoplasia con 764 casos (18,33%), la Hiperplasia Fibrosa por Prótesis Dental con 447 casos (10,73%). En referencia a las diferentes localizaciones anatómicas mayormente afectadas en este estudio: el Reborde Alveolar ocupó el primer lugar (1134 casos; 27,2%), seguida por Los Carrillos (639 casos; 15,33%), Labio Inferior (522 casos; 12,5%), Encías (493 casos; 11,8%).En referencia al grado de Concordancia global entre el Diagnóstico Clínico e Histopatológico fue del 75,9 % de los casos (3.161 casos de 4.166). Situación que nos permite asumir que la concordancia global es satisfactoria.

A study of documentary, retrospective, cross. The study population was represented by a total of 9,000 stories diagnosed at the Central Laboratory of Oral Histopathology "Dr. Pedro Tinoco " in the Faculty of Dentistry at UCV, during the period 1988-2008 . The sample studied was composed of a total of Four Hundred Sixty Six Thousand (4,166 ) cases , which were selected intentionally not random from the population above following inclusion and exclusion criteria . Injury prevalence Benign and Potentially Malignant Disorders affecting Mucosa is high ( 46.2 %) compared to the total study sample (9000 cases). According to Age Group observed an age range between 15 and 97 years , an average of 47.3 years and 16.5 Desv.Tip (Y ± s : 47.3 ± 16.5). Regarding the Gender distribution in our study there is a prevalence of oral mucosal lesions in females (69.7 %). Clinical diagnoses based on 77 different lesions were identified. The Traumatic fibroma was the most common injury in 1042 patients (25.01%), followed by leukoplakia with 764 cases (18.33%), Fibrous Hyperplasia By Dental Implants with 447 cases (10.73%). Referring to different anatomical locations most affected in this study: Alveolar Flange ranked first (1134 cases , 27.2 %), followed by The Cheeks (639 cases , 15.33%), Lower Lip (522 cases; 12.5%), Gum (493 cases, 11.8%). Referring to the degree of overall concordance between the Clinical and Histopathological diagnosis was 75.9% of cases (3,161 of 4,166 cases). This situation allows us to assume that the overall agreement is satisfactory.

Leucoplasia verrucosa proliferativa: a propósito de un caso clínico / Proliferative verrucous leukoplakia: a clinical case

La Leucoplasia Verrucosa Proliferativa (LVP) es una placa blanca, verrucosa, exofítica, de crecimiento lento, que no se desprende al raspado y que tiende a comprometer diversos sitios de la mucosa oral. Es resistente al tratamiento independiente de la terapia adoptada y presenta una alta tasa de recidiva posterior al tratamiento quirúrgico. Desde 1985, cuando fue descrita por primera vez por Hansen, hasta le fecha, se ha mantenido como una entidad patológica compleja. Reportamos un caso de una paciente de sexo femenino de 72 años de edad que consulta por una lesión blanca, verrucosa, asintomática, que no se desprende al raspado, en el borde y vientre lingual y piso de boca. Se realizaron 2 biopsias incisionales del borde lateral de la lengua. Al examen microscópico se observó en ambas biopsias un grueso revestimiento epitelial acantósico, con marcada hiperparaqueratosis, una membrana basal nítida y cambios displásicos mínimos. Al mes de realizadas las biopsias la lesión presentó recidiva, manteniendo las mismas características clínicas encontradas inicialmente. Considerando la evolución, comportamiento biológico y las características histopatológicas, la lesión se diagnosticó como una LVP. Hasta la fecha, no hay protocolo de tratamiento establecido para estas lesiones. En este caso en particular, tomando en cuenta la extensión de la lesión, los sitios comprometidos, las escasas atipias presentes al examen histopatológico, la edad y escaso nivel socioeconómico de la paciente, se decidió no realizar la remoción quirúrgica de la lesión y mantenerla en control clínico cada 3 meses. Después de varios controles realizados durante un periodo de 3 años, se observó que la lesión mantuvo sus características clínicas iniciales. Esto confirma que haber optado por un tratamiento conservador, en este caso en particular de LVP, fue la decisión correcta...

The proliferative verrucous leukoplakia (PVL) is a white plate, wart-like, exophytic , slow growth , which does not follow the scaling that tends to compromise various oral mucosal sites . It is resistent to independent therapy and has a high rate of recurrence after surgical treatment. Since 1985, when it was first described by Hansen, and to date it has remained a complex pathological disorder. We report a case of a 72-year-old female patient who complains of a white, verrucous and asymptomatic lesion. The lesion does not detach by scraping the edge, lingual belly or mouth floor. Two Incisional biopsies were performed on lateral border of the tongue. Upon microscopic examination of both biopsies, thick epithelial lining, with marked hyperparakeratosis, a basement membrane, and minimal dysplasia alterations were observed. One month following biopsies of the lesion were performed, lesion relapsed and maintained the same clinical features found initially. Considering the evolution, biological behavior and histopathological features, the lesion is diagnosed as an PVL. To date, there is no established treatment protocol for these injuries. In this particular case, taking into account the extent of the injury, compromised sites, the few atypia present histopathological examination, age and low socioeconomic level of the patient, it was decided not to perform surgical removal of the lesion and maintain clinical monitoring every 3 months. Following several examinations carried out over a three-year period, it was observed that the injury kept initial clinical features. This confirms that having opted for conservative treatment, in this particular case of PVL, was the right decision...

Análise comparativa da expressão imuno-histoquímica da via PI3K-AKT-mTOR em displasias epiteliais, lesões irritativas e carcinomas espinocelulares / Comparative analysis of the immunohistochemical expression of PI3K-AKT-mTOR in epithelial dysplasia, irritative lesions and squamous cell carcinomas

A leucoplasia é a mais comum das lesões potencialmente malignas (LPM) da mucosa bucal acometendo cerca de 2% da população. A via PI3K- AKT-mTOR, tem papel importante na carcinogênese em diversos tumores, incluindo o câncer de cabeça e pescoço e estudos têm apontado os inibidores do mTOR como promissores agentes de avaliação terapêutica. Desta forma, no presente estudo avaliamos a expressão imuno-histoquímica de lesões bucais diagnosticadas clinicamente como leucoplasias, comparando-as com carcinomas espinocelulares (CEC), hiperqueratoses irritativas (HI) e mucosa normal (MN). Foram avaliados 186 casos, divididos em 5 grupos tais como displasia epitelial de alto risco (DAR), displasia epitelial de baixo risco (DBR), CEC, HI e MN. Os casos foram retirados do arquivo do Serviço de Patologia Cirúrgica da Disciplina de Patologia Bucal da Faculdade de Odontologia da Universidade de São Paulo. As informações clínicas, relativas ao sexo e idade dos pacientes e localização das lesões foram compiladas. Todas as lesões selecionadas foram observadas ao HE por dois patologistas, ao microscópio de luz para confirmação dos diagnósticos. As proteínas pesquisadas incluiram: pAKT, pmTOR, pS6, e p4EBP1. A marcação dos diversos anticorpos foi quantificada com o auxílio da aquisição de imagens realizada com o uso de um fotomicroscópio. Na imagem capturada (aumento de 400x), foi observada a presença ou ausência de células marcadas, bem como, numa segunda análise, a quantidade percentual das mesmas.

Na primeira análise, o padrão de marcação foi classificado em positivo e negativo e, na segunda, foi classificado em graus de 0 a 3. As variáveis do estudo foram avaliadas pelos testes Qui-quadrado e o teste F, ANOVA e posteriormente foi realizada uma regressão logística univariada. Entre todos os casos de mucosa oral normal, foi encontrada positividade somente para o anticorpo pS6, em 50%dos casos; nas HI houve marcações positivas para a pS6 (em 54,8% dos casos) e p4EBP1 (em 22,6% dos casos). Nas DBR foi observada a imunorreatividade aos anticorpos pS6 (em 67,4% dos casos), pAKT(em 56,2% dos casos), p4EBP1(em 41,7%dos casos) e pmTOR (em 29,2% dos casos), já nas DAR houve positividade para a pS6 (em 74% dos casos), pAKT (em 68% dos casos), p4EBP1 (em 44% dos casos) e pmTOR (em 28% dos casos). Os CECs expressaram pAKT ( em 83,3% dos casos), pS6 (em 77,4% dos casos), p4EBP1(em 50% dos casos) e pmTOR (em 50%dos casos). Quando se considerou o resultado da marcação positiva ou negativa, houve diferença estatisticamente significante, ente os grupos, em relação ao número de casos que expressaram as proteínas pAKT, pmTOR e p4EBP1, sendo que o grupo dos CECS foi o que apresentou maior frequência de imunorreatividade para todos os anticorpos estudados. Comparando-se apenas as lesões de CEC e DEO, observou-se que mais casos de CEC foram positivos para pAKT e pmTOR e não observou-se diferença na expressão do p4EBP1. Logo, podemos concluir que todas as proteínas estudadas, exceto a pS6, representam bons biomarcadores no que se concerne à diferenciação entre MN, HI, DEO e CEC. Entretanto somente as proteínas pAKT e pmTOR podem ser relacionadas à carcinogênese oral .

Leukoplakia is the most common potentially malignant lesion (PML) of the oral cavity affecting approximately 2% of the population. PI3K-AKT-mTOR pathway plays an important role in carcinogenesis in many tumors, including head and neck cancer, and several studies have showed mTOR inhibitors as promising therapeutic agents. In this study we evaluated the immunohistochemical expression of oral lesions diagnosed clinically as leukoplakia and squamous cell carcinoma (SCC), comparing them to normal mucosa (NM) and frictional hyperkeratosis (FR). We evaluated 186 cases, divided into 5 groups including high risk dysplasia (HRD), low risk dysplasia (LRD), SCC, NM and FR. The cases were obtained from the archives of the Oral Pathology Laboratory of the School of Dentistry of the University of São Paulo. Clinical information regarding sex, age of the patient and location of the lesions were compiled. The slides (HE staining) were observed by two pathologists and all cases were re-evaluated under light microscope. The proteins investigated were: pAKT, pmTOR, PS6, and p4EBP1. The staining pattern of the antibodies was quantified by acquiring images using a photomicroscope. In the captured image (400x magnification), the total of counted labeled cells, were divided by the total number of cells present in the field captured. The staining pattern was classified into positive and negative and also divided into degrees starting from 0 to 3.

The study variables were evaluated by chi-square test, ANOVA F and univariate logistic regression analysis. Among all the cases of MN, positivity was found only for pS6 (50% of cases); in FH cases immunoreactivity was observed in pS6 (54.8% of cases) and 4EBP1 (22.6% of cases). In LRD immunoreactivity was observed in pS6 (67.4% of cases), pAKT (56.2% of cases), p4EBP1 (41.7% of cases) and pmTOR (29.2% of cases), while for HRD cases positivity was found for pS6 (74% of cases), pAKT (68% of cases), p4EBP1 (44% of cases) and pmTOR (28% of cases). In SCCs cases positivity was found for pAKT (83.3% of cases), PS6 (77.4% of cases), p4EBP1 (50% of cases) and pmTOR (50% of cases). Statistically significant differences were observed in all positive study groups for the proteins pAKT, pmTOR and p4EBP. After the evaluation of SCC and the oral dysplasia groups, there were statistically significant differences for the study groups that showed imunorretivity for the proteins pAKT and pmTOR. Therefore, we conclude that all the proteins of the study are good biomarkers to differentiate normal tissue from OD and SCC, but only pAKT and pmTOR proteins could be related to carcinogenesis.

Expressão imuno-histoquímica das proteínas ki-67, MCM3 e p27 em leucoplasias e carcinoma epidermóide de boca / Imunohistochemical expression of ki-67 protein, MCM3 and p27 in leukoplakia and squamous cell carcinoma of the mouth

O propósito deste estudo foi identificar o padrão de expressão de Ki-67, MCM3 e p27 em mucosa normal (MN), em leucoplasias de orais ( leves, moderadas e intensas ) e em carcinomas epidermoides de boca (CEB), com objetivo de sugerir a participação dessas proteínas na aquisição do fenótipo malígno. Os espécimes foram removidos de 37 pacientes com leucoplasias bucais (13 com displasias leves- DL, 12 com displasias moderadas-DM e 12 com displasias intensas-DI). Onze amostras de mucosa normal de soalho bucal (MN) e 50 amostras de CEB de soalho e língua de pacientes não tratados foram incluídas neste estudo. As amostras foram imunomarcadas com anticorpos contra, Ki-67, MCM3 e p27. O teste Kruskal Wallis e o teste de Dunns foram usados para determinar a diferença dos grupos entre si. Para avaliar a correlação das proteínas entre si foi utilizado o teste de correlação de Pearson. Ki-67 mostrou índices de marcação estatisticamente maior em casos de CEB quando comparados com o grupo que continha MN (p<0.001) e DL (p<0.01) e índices de marcação estatisticamente menor na MN quando comparada com os grupos que continham DM e DI (p<0.05). A proteína p27 mostrou índice de expressão estatisticamente menor quando as amostras com CEB foram comparadas com os grupos que continham a MN, DL; DM e DI (p<0.001). A proteína MCM3 mostrou índices de marcação estatisticamente menor no grupo que continha a MN quando se correlacionou com o que apresentava DI e CEB (p<0.001) e o grupo com DL mostrou índices estatisticamente menores quando foi correlacionado tanto com o grupo de DI (p0.01)Outros resultados dignos de nota foram a significante correlação entre as proteínas MCM3 e p27 ( r=0.31 e p< 0.03 ), Ki-67 e p27 ( r=0.31 e p< 0,03281 ) e MCM3 e ki- 67 ( r=0,69 p< 0,01 ) em CEB e MCM3 e p27 ( r=0.58 e p< 0.05 ) em displasia ...

The aim of this study was to identify the expression of MCM3, Ki-67 and p27 in normal mucosa (MN) in leukoplakia and Oral Squamous Cell Carcinoma Epidemiology (OSCCE), and to determine whether altered expression could serve as a prognostic marker of a malignant progression of dysplasia lesions. The samples were collected from 37 patients with oral leukoplakia (13 with mild dysplasia - MLD, 12 with moderate dysplasia - MD and 12 with severe dysplasia - SD). Eleven samples of mouth floor mucocele (M) and 50 floor and tongue samples OSCCE of untreated patients were included in this study. Immunohistochemical MCM3, Ki-67 and p27 expression of all the groups was analyzed. Kruskal Wallis and Dunns test were used to determine differences among groups, and a Pearson correlation test was used to evaluate the correlation between the proteins. Ki-67 expression was higher in OSCCE than M (p0.001) and MLD (p0.01) groups, and there was a lower expression in MN compared with MD and ID (p0.05). Ki-67 expression did not show significant difference between MD, SD and OSCCE. Regarding p27, its expression was lower in OSCCE compared with M, MD and SD (p<0,001). MCM3 expression was lower in M compared with SD and OSCCE (p0.001) and MLD showed a lower expression when compared SD (p0.01) and OSCCE (p0.001). The present study showed that MCM3 could be a better marker than Ki67 for evaluation dysplastic oral lesions.

Leucoplasia verrugosa proliferativa / Proliferative verrucous leukoplakia

Una leucoplasia es según la definición de la Organización Mundial de la Salud (OMS) una placa blanca de la mucosa bucal, de cuestionableriesgo, habiéndose excluido otras enfermedades conocidas o desórdenes que no tienen aumentado el riesgo de transformación encáncer. Su diagnóstico se realiza por exclusión de otras enfermedades con aspecto clínico similar, pero que no acarrean riesgo aumentadode cáncer. Es el desorden potencialmente maligno que sufre transformación con mayor frecuencia, con rango de transformación entreel 0,13 y el 17.5%Una variante rara de la leucoplasia, es la leucoplasia verrugosa proliferativa (LVP), descripta por primera vez en 1985 por Hansen etal. Anterior a esa fecha era conocida como papilomatosis florida. La LVP, fue clasificada por la OMS en 2005 como un desorden potencialmente maligno (OMS 2005) por presentar una alta probabilidad de transformarse en un carcinoma espinocelular o un carcinomaverrugoso. Esto indica un comportamiento biológico agresivo.En la mayoría de los casos el diagnóstico de LVP es retrospectivo, lo que enlentece su tratamiento. Su etiología es incierta, pudiendo estar relacionada con el virus del papiloma humano (VPH), con el virus de Epstein-Barr, o con infecciones por cándida, pero aún no hasido posible establecer una correlación definitiva. Sigue considerándosele como lesión de etiología desconocida.

A leukoplakia is, as defined by the World Health Organization (WHO), a white plate of the oral mucosa, of questionable risk having excluded other known diseases or disorders that have no increased risk of cancer transformation. The diagnosis is made by excludingother diseases with similar clinical appearance but carry no increased risk of cancer. It is the potentially malignant disorder that most often suffers transformation within a range between 0.13 and 17.5%. A rare variant of leukoplakia is the proliferative verrucous leukoplakia (PVL) first described in 1985 by Hansen et al. Previously it wasknown as florid papillomatosis. WHO in 2005 classified the PVL as a potentially malignant disorder (WHO 2005) for presenting a high probability of becoming a squamous cell carcinoma (squamous) or warty carcinoma; this indicates an aggressive biological behavior.In most cases the diagnosis of PVL is retrospective, slowing the treatment. Its etiology is uncertain and may be related to human papillomavirus (HPV), the Epstein-Barr virus or even yeast infections, but has not been possible yet to establish a definitive correlation. Still it is considered an injury of unknown etiology.

Oral leukoplakia manifests differently in smokers and non-smokers

Oral leukoplakias (OL) are potentially malignant lesions that are typically white in color. Smoking is considered a risk factor for developing OL, and dysplastic lesions are more prone to malignant transformation. The aim of this study was to describe the clinical features observed in dysplastic and non-dysplastic OL in both smokers and non-smokers. A total of 315 cases of OL were retrieved and separated into either dysplastic or non-dysplastic lesions, and these cases were further categorized as originating in either smokers or non-smokers. Frequencies of the type of OL lesion, with respect to whether the patients smoked, were established. The results demonstrated that 131 cases of OL were dysplastic (74 smokers and 57 non-smokers), and 184 were non-dysplastic (96 smokers and 88 non-smokers). For OL cases in smokers for which information about alcohol consumption was also available (84 cases), the results revealed no significant difference in the amount of dysplastic and non-dysplastic lesions. Dysplastic lesions were more frequent in male smokers and in non-smoking females. The median age of smokers with cases of OL was significantly lower than in non-smokers; the lowest median ages were observed for female smokers with dysplastic OL. The most frequent anatomical sites of dysplastic lesions were the floor of the mouth in smokers and the tongue in non-smokers. Dysplastic lesions in smokers were significantly smaller than non-dysplastic lesions in non-smokers. Being a male smoker, being female, being younger, and having smaller lesions were associated with dysplastic features in OL. These clinical data may be important for predicting OL malignant transformation.

Leucoplasia bucal: levantamento epidemiológico dos casos encontrados no Serviço de Diagnóstico Histopatológico do Instituto de Ciências Biológicas da Universidade de Passo Fundo / Oral leukoplakia: epidemiological survey of cases found at the Histopathologic Diagnosis Service of the Institute of Biological Sciences, University of Passo Fundo

Objetivo: O presente estudo teve como objetivo realizar um estudo epidemiológico observacional transversal dos casos de leucoplasia bucal registrados no Serviço de Diagnóstico Histopatológico do Instituto de Ciências Biológicas (ICB) da Universidade de Passo Fundo (UPF).Materiais e Métodos: Foram considerados os casos diagnosticados como “leucoplasia bucal” entre os anos de 1989 e 2011. Os dados que dizem respeito à idade, sexo eraça dos pacientes, bem como os dados de localização da enfermidade na cavidade bucal foram obtidos das requisições de exame histopatológico de cada paciente. Foram observados a presença de hábitos deletérios nos pacientes acometidos e as características clínicas das lesões levantadas. Os dados coletados foram analisados por meio de estatística descritiva de frequência e expressos em tabelas e/ou gráficos, a fim de serem confrontados com os dados da literatura. Resultados e conclusão: Pôde-se inferir que a época da vida mais afetada pela leucoplasia foi a 7ª década da vida, a cor branca foi predominante, o sexo masculino o mais afetado e a região mais acometida foi a mucosa jugal na linha de oclusão. Exposição solar, trauma e fumo foram as principais causas encontradas no estudo, porém houve muitos laudos incompletos, o que leva à dúvida quanto aos demais casos (a maior parte neste estudo). O tempo de evolução das lesões foi relativamente rápido, a maioria aparecendo de 0-6 meses em boca, e normalmente assintomáticas. A coloração branca, sem presença de displasia, foi predominante e as características das lesões se assemelharam em todos os casos.

Objective: This study aimed to conduct a transversal observational epidemiological study in reported cases of oral leukoplakia in the Department of Diagnostic Histopathology of the Institute of Biological Sciences (ICB), University of Passo Fundo (UPF). Materials and Methods: We considered the cases that were diagnosed as “oral leukoplakia” between the years 1989 and 2011. The data pertaining to age, sex and race of patients, as well as the location data of the disease in the oral cavity were obtained from histopathological examination of requests for each patient. We observed the presence of harmful habits in affected patients and the clinical features of raised lesions. The collected data were analyzed using descriptive statistics and expressed as frequency tables and/or graphics in order to be compared with data found in literature. Results and conclusion: It might be inferred that the period of life most affected by leukoplakia was the 7th decade of life, was predominantly white, male sex the most affected and most affected region was the buccal mucosa in the line of occlusion. Sun exposure, smoking and trauma were the main causes in the study, but there were many reports are incomplete, which leads to doubt as to the other cases (most of this study). The time evolution of the lesions was relatively quick, most appearing tomouth from 0-6 months, and usually asymptomatic. The white color, without the presence of dysplasia was predominant and lesion characteristics were similar in all cases.

Incidencia de la eritroleucoplasia en la cavidad bucal / Incidence of erythroleukoplakia in the oral cavity

Se efectuó un estudio descriptivo y transversal de 20 mujeres y hombres mayores de 19 años, adictos al tabaco, atendidos en la consulta estomatológica del Policlínico de Especialidades del Hospital Provincial Docente Saturnino Lora Torres de Santiago de Cuba, desde septiembre del 2007 hasta igual mes del 2010, con vistas a evaluar los resultados del diagnóstico clinicohistopatológico, obtenido del examen de la cavidad bucal y de la biopsia realizada a los pacientes con eritroleucoplasia. Las muestras fueron fijadas y procesadas por la técnica convencional de inclusión en parafina, con lo cual se confirmó la presencia de cambios tisulares. En la casuística prevalecieron el sexo masculino, la ausencia de manifestaciones clínicas y la mucosa de carrillo como el sitio de ubicación más susceptible. Asimismo, las alteraciones hísticas más comunes fueron la hiperqueratosis y el infiltrado inflamatorio subepitelial.

A descriptive and cross-sectional study of 20 women and men older than 19 years, who were heavy smokers, assisted in the Stomatology Department of the Specialties Polyclinic from Saturnino Lora Torres Provincial Teaching Hospital in Santiago de Cuba was carried out from September, 2007 to the same month of 2010, with the objective of evaluating the results of the clinico-histopathological diagnosis, obtained from the examination to the oral cavity and from the biopsy carried out to patients with erythroleukoplakia. The samples were fixed and processed through the conventional technique of inclusion in paraffin, which confirmed the presence of tissue changes. Male sex, the absence of clinical manifestations and the cheek mucosa as the most susceptible location prevailed in the case material. Also, the most common tissue alterations were the hyperkeratosis and the subepithelial inflammatory infiltrate.

Coexpression of p53 and Ki 67 and lack of c-erbB2 expression in oral leukoplakias in India

Oral cancer is commonly preceded by premalignant lesions and conditions. The clinician's ability to identify lesions at an increased risk of cancer development is critical for its control. The purpose of this study was to compare the expression of tumor suppressor gene p53, proliferation marker Ki-67, and oncogene c-erbB2 and to evaluate the relevance of their co-expression in the diagnosis of, and prognosis for, oral leukoplakia. In the present study, the expression of biomarkers was studied immunohistochemically in 55 cases of leukoplakia (26 without dysplasia, 29 with dysplasia) and 10 cases of normal epithelia. The Labeling Indices (LI) of p53 and Ki-67 were found to increase significantly with an increase in the grade of dysplasia. A significant correlation was also found between the LI of p53 and that of Ki-67. It was also observed that c-erbB2 expression was only cytoplasmic, indicating incomplete receptor degradation. Hence, it can be concluded from the present study that the increased expression of p53 and Ki-67 with an increase in the grade of dysplasia suggests that their co-expression may be used for the identification of high-risk lesions. Also, c-erbB2 has no pathogenetic role in early carcinogenesis in the studied population, although incomplete receptor degradation, as evidenced by cytoplasmic staining, may indicate an early change.