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

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

Queilite esfoliativa: diagnóstico diferencial e tratamento / Queilitis exfoliativa: diagnóstico diferencial y tratamiento / Exfoliative cheilitis: differential diagnosis and treatment

Introdução: a queilite esfoliativa é uma condição dermatológica incomum que ocorre principalmente em mulheres jovens e que afeta o vermelhão dos lábios. Embora a doença seja de etiologia desconhecida, ela tem sido associada a períodos de estresse e ansiedade, como também a hábitos parafuncionais. O seu diagnóstico e manejo constituem um desafio devido à semelhança clínica entre a queilite esfoliativa e outras lesões labiais, o que muitas vezes resulta em recorrência. Objetivo: relatar dois casos clínicos de queilite esfoliativa enfatizando o diagnóstico diferencial com outras lesões que podem acometer os lábios. Relato de Casos: O primeiro caso ocorreu em um paciente do sexo masculino, 21 anos, leucoderma, com queixa de que há dois anos sentia ardência e coceira nos lábios associada a formação de crostas. Ele relatou ter realizado tratamento prévio e possuir problemas de saúde de ordem geral. Exames complementares foram realizados e não mostraram alterações. Assim, a hipótese de queilite esfoliativa foi estabelecida. O paciente foi submetido à biópsia incisional, sob anestesia local, no qual o exame histopatológico confirmou o diagnóstico clínico de queilite esfoliativa, sendo tratado com laserterapia, porém não houve sucesso no tratamento. No segundo caso, uma paciente do sexo feminino, 43 anos, melanoderma, exibindo manchas, fissuras e crostas nos lábios, além de prurido como sintomatologia. Foram solicitados exames complementares que apresentaram padrões de normalidade, assim, o diagnóstico clínico foi de prurigo actínico. Após a realização de biópsia incisional, sob anestesia local, o diagnóstico de queilite esfoliativa foi estabelecido. A paciente foi tratada com corticosteroide tópico, havendo regressão da lesão. Conclusão: o diagnóstico e manejo clínico da queilite esfoliativa é um desafio, deste modo, se faz necessário o estabelecimento de um diagnóstico correto, descartando a hipótese de outras doenças com o auxílio de exames complementares(AU)

Introducción: la queilitis exfoliativa es una condición dermatológica inusual que ocurre principalmente en mujeres y que afecta la superfície de los labios. Aunque es una enfermedad de causa desconocida, ha sido asociada a estrés y ansiedad, así como a hábitos parafuncionales. Su diagnóstico y manejo es un desafío debido a la similitud clínica entre la queilitis exfoliativa y otras lesiones labiales, ya que a menudo estas lesiones tienen recurrencia. Objetivo: describir dos casos clínicos de queilitis exfoliativa enfatizando en el diagnóstico diferencial. Presentación de casos: el primer caso ocurrió en un paciente del sexo masculino de 21 años, raza blanca. Relató que hace dos años sentía ardor en los lábios asociado a la formación de costras. Afirma haber realizado tratamiento previo y no presentar ningún problema de salud. Se realizaron exámenes complementarios y no mostraron ninguna alteración. Así, se estableció la hipótesis de queilitis exfoliativa. El paciente fue sometido a biopsia incisional, bajo anestesia local, en el cual el examen histopatológico confirmó el diagnóstico clínico de queilitis exfoliativa, siendo tratado con laserterapia, sin embargo, no hubo éxito en el tratamiento. En el segundo caso, una paciente de sexo femenino, 43 años, raza negra, exhibiendo manchas, fisuras en los labios, además de prurito como sintomatología. Se solicitaron exámenes complementarios que presentaron valores dentro de la normalidad, por lo que el diagnóstico clínico fue de prurito actínico. Después de la realización de la biopsia incisional, bajo anestesia local, fue establecido el diagnóstico de queilitis exfoliativa. La paciente fue tratada con corticoesteroides tópicos, habiendo regresión de la lesión. Conclusiones: el diagnóstico y manejo clínico de la queilitis exfoliativa es un desafío, por lo que se hace necesario el establecimiento de un diagnóstico correcto, excluyendo otras afecciones con el apoyo de exámenes complementarios(AU)

Introduction: exfoliative cheilitis is an infrequent skin condition that occurs mostly in women, affecting the skin of the lips. Though its etiology is unknown, it has been associated to stress and anxiety, as well as to parafunctional habits. Diagnosis and management are challenging, due to the clinical similarity between exfoliative cheilitis and other lesions of the lips, since these are often recurrent. Objective: describe two clinical cases of exfoliative cheilitis, focusing on the differential diagnosis. Case presentation: the first case was a white male 21-year-old patient who reported having had a burning sensation on his lips associated to crust formation for two years. The patient stated having been under treatment and being in good general health. Complementary tests were indicated which did not reveal any alteration. Thus, the hypothesis of exfoliative cheilitis was put forth. Incisional biopsy was performed under local anesthesia, histopathological examination confirming the clinical diagnosis of exfoliative cheilitis. Laser therapy was indicated, but the treatment was not successful. The second case was a black female 43-year-old patient presenting with spots and fissures on her lips, as well as itching. Complementary tests were indicated which yielded normal values, and thus the clinical diagnosis was actinic prurigo. Incisional biopsy performed under local anesthesia led to the diagnosis of exfoliative cheilitis. The patient was treated with topical corticosteroids, with regression of the lesion. Conclusions: exfoliative cheilitis diagnosis and clinical management are challenging, hence the need to make an accurate diagnosis, excluding other conditions with the aid of complementary tests(AU)

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.

Avaliação da expressão de ß-catenina e ciclina D1 como biomarcadores preditivos para o câncer de lábio / Evaluation of ß-catenin and cyclin D1 expression as predictive biomarkers for lip cancer

Um dos objetivos da pesquisa científica, atualmente, é encontrar biomarcadores que possam auxiliar na definição da probabilidade de progressão das lesões orais displásicas, e ainda sejam capazes de identificar os principais agentes moleculares envolvidos na carcinogênese de um determinado tipo de tumor. Assim, o objetivo deste estudo foi investigar a expressão de ß-catenina, ciclina D1 e Ki-67 em 15 espécimes de epitélio oral normal, 45 queilites actínicas displásicas e em 30 carcinomas espinocelulares de lábio. Essa amostra foi constituída por pacientes tratados na Faculdade de Medicina de Botucatu (Brasil) e no Hospital Clínico San Cecílio de Granada (Espanha). O grau de displasia epitelial e de diferenciação tumoral foi classificado com base nos critérios definidos pela Organização Mundial da Saúde. A avaliação dos biomarcadores foi realizada por meio da técnica imunohistoquímica, dividindo a espessura do epitélio em quatro compartimentos (basal, suprabasal, terço médio e terço superior) para o grupo controle e para as queilites actínicas e em três compartimentos (basal, suprabasal e região interna) para o grupo dos carcinomas espinocelulares de lábio. Para a comparação da média de expressão de cada marcador, nas diferentes localizações do epitélio foi utilizado o teste estatístico de Kruskal-Wallis. Para a correlação da expressão dos três marcadores entre os grupos foi utilizada a correlação de Spearman, com nível de significância de 5%. Os resultados demonstraram uma perda discreta da expressão membranosa de ß-catenina na camada basal das queilites actínicas com displasia epitelial intensa (Cis) e nos carcinomas espinocelulares de lábio, assim como uma expressão citoplasmática e nuclear, discreta e diretamente proporcional à desorganização epitelial nas camadas basal e suprabasal das queilites actínicas e carcinomas espinocelulares de lábio. Notou-se também um aumento da expressão de ciclina D1 e Ki-67 na camada basal à medida que aumentava a desorganização epitelial. Houve uma associação estatisticamente significativa da expressão de ciclina D1 e Ki-67 na camada suprabasal do grupo controle (p=0,030) e das queilites actínicas (p=0,001) e ainda na região interna dos carcinomas espinocelulares de lábio (p=0,000). Não houve correlação significativa entre as expressões nucleares de ß-catenina e de ciclina D1. Nossos resultados reforçam que a ß-catenina, a ciclina D1 e o Ki-67, podem ser utilizados como biomarcadores preditivos para o câncer de lábio. Além disso, sugerem que a ß-catenina e a ciclina D1 participam da carcinogênese labial, em eventos independentes da via de sinalização/Wnt.(AU)

One of the goals of scientific research today is to find predictive biomarkers that can help define the probability of progression of dysplastic oral lesions, and are still able to identify key molecular agents involved in the carcinogenesis of a particular type of tumor. The objective of this study was to investigate ß-catenin, cyclin D1 and Ki-67 expression in 15 specimens of normal oral epithelium, 45 dysplastic actinic cheilitis and 30 squamous cell carcinoma of the lip. This sample consisted of patients treated at the Botucatu Medicine School (Brazil) and the Clinical Hospital San Cecilio of Granada (Spain). The degree of epithelial dysplasia and tumor differentiation was classified based on the criteria defined by the World Health Organization. The evaluation of biomarkers was performed by immunohistochemical technique, dividing the thickness of the epithelium into four compartments (basal, suprabasal, middle third and upper third) for the control group and actinic cheilitis and three compartments (basal, suprabasal and inner region) to the group of squamous cell carcinoma of the lip. For comparing the average expression of each marker in different locations of the epithelium we used the statistical test of Kruskal-Wallis. For the correlation of the three markers expression between the groups was used Spearman, with 5% significance level. The results showed a slight loss of membranous expression of ß-catenin in the basal layer of actinic cheilitis with severe epithelial dysplasia (Cis) and squamous cell carcinoma of the lip, and a cytoplasmic and nuclear expression, slight and directly proportional to the epithelial disorganization in layers basal and suprabasal of actinic cheilitis and squamous cell carcinoma of the lip. It was also noted an increase in expression of cyclin D1 and Ki-67 in the basal layer as increased epithelial disorganization. There was a statistically significant association of cyclin expression D1 and Ki-67 in the suprabasal layer of the control group (p=0.030) and actinic cheilitis (p=0.001) and also in the inner region of squamous cell carcinoma of the lip (p=0.000). There was no significant correlation between the nuclear expression of ß-catenin and cyclin D1. Our results emphasize that ß-catenin, cyclin D1 and Ki-67 can be used as predictive biomarkers for lip cancer. Moreover, they suggest that ß-catenin and cyclin D1 acts on the lip carcinogenesis, in independent events signaling pathway/Wnt.(AU)

Estudo da expressão de CLIC4 e proteínas associadas em queilites actínicas e carcinomas de células escamosas de lábio inferior / Study of the expression of CLIC4 and associated proteins in actinic cheilitis and lower lip squamous cell carcinomas

A proteína do canal de cloro intracelular 4 (CLIC4) regula a passagens dos íons de cloro e relaciona-se com a proteína p53, fator de necrose tumoral α (TNF-α), fator de crescimento transformante-ß (TGF-ß) e com a diferenciação de fibroblastos em miofibroblastos (-SMA) em alguns cânceres humanos. O objetivo desse estudo foi analisar a expressão imuno-histoquímicade CLIC4 e proteínas associadas em queilitesactínicas (QA) e carcinomas de células escamosas de lábio inferior (CCELI), bem como verificar a relação destas entre si e com as características clínicas e morfológicas das lesões.A amostra foi composta de 50casos de QAs e 50de CCELIs com dados clínicos, que inicialmente foram submetidos ao estudo morfológico para sua gradação do risco de transformação maligna (sistema binário) e do grau histológico de malignidade (Bryne, 1992), respectivamente.Todos os casos foram submetidos ao método da imunoperoxidase usando os anticorpos paraCLIC4, p53, TGF-, TNF- e - SMA, os quais foram submetidos à análise semiquantitativa, com exceção de p53, que inicialmente foi analisado de forma quantitativa e em sequência categorizada como as demais. Para a análise da expressão de CLIC4 foi considerada sua localização celular.Comparações das imunomarcações com os parâmetros clínicos e morfológicos das lesões foram realizadas pelo teste U de Mann-Whitney e o coeficiente de Spearmanfoi calculado para avaliar correlações entre as proteínas. A expressão nuclear da CLIC4 e TGF-ß estava aumentadaem QAs de baixo risco, quando comparada ao grupo de alto risco (p<0.0001), enquantoCLIC4 citoplasmática,p53 e TNF-α exibiram maior expressão em QAs de alto risco (p<0.05). No que diz respeito às características clínicas e morfológicas dos CCELIs, a expressão de CLIC4 citoplásmatica foi maior nos casos apresentando metástase linfonodal, casos com estágios clínicos mais avançados ou com alto grau de malignidade (p = 0,005; p = 0,029; p<0,0001). A expressão de p53 foi maior em CCELIs de alto grau de malignidade (p= 0,001) e a TGF-ß diminuiu significativamente conforme o avanço do estágio clínico e do grau histológico dos tumores (p< 0,05).As QAs exibiram uma expressão aumentada de CLIC4 (no núcleo, ou núcleo e citoplasma) e TGF-ß, comparadas aos CCELIs (p < 0,0001). Em contraste, houve aumento na marcação de CLIC4 citoplasmática e α-SMA nos casos de CCELI, quando comparados às QAs (p < 0,0001).Nas QAs observou-se correlação negativa entre a expressão de CLIC4 nuclear ea CLIC4 citoplasmática (r = -0,554; p = <0,0001), e entre a marcação de TGF-ß e α-SMA (r = -0,309; p = 0,029). Nos carcinomas, a expressão de p53 exibiu correlação positiva com TNF-α (r = 0,528; p = 0,0001) e αSMA (r = 0,435; p = 0,002).Os nossos resultados sugeremque uma mudança no padrão de expressão nuclear para citoplasmática de CLIC4 está envolvida no processo decarcinogênese labial, acompanhada de alterações na expressão de p53, TGF-ß, TNF-α e α-SMA, e se relacionamcom alguns dos aspectos morfológicos e clínicos das QAs e CCELIs (AU).

The intracellular chloride channel protein 4 (CLIC4) regulates chloride ions and is related to p53, tumor necrosis factor α (TNF-α), transforming growth factor-ß (TGFß), and with the differentiation of fibroblasts in myofibroblasts (-SMA) in some human cancers. The objective of this study was to analyze the immunohistochemical expression of CLIC4 and associated proteins in actinic cheilites (AC) and squamous cell carcinomas of the lower lip (SCCLL), as well as to verific their relationship with each other and with the clinical and morphological characteristics of the lesions . The sample consisted of 50 cases of AC and 50 of SCCLL with clinical data, which were initially submitted to the morphological study for their gradation of malignant transformation risk (binary system) and histological grade of malignancy (Bryne, 1992). All cases were submitted to the immunoperoxidase method using CLIC4, p53, TGF-ß, TNF- and - SMA antibodies, which were submitted to semiquantitative analysis, except for p53, which was initially analyzed quantitatively and a categorized sequence like the others. For the analysis of CLIC4 expression, its cellular location was considered. Comparisons of the immunoblots with the clinical and morphological parameters of the lesions were performed by the Mann-Whitney U test and the Spearman coefficient was calculated to evaluate correlations between the proteins. Nucleic expression of CLIC4 and TGF-ß was increased in low-risk AC compared to high-risk group (p <0.0001), whereas cytoplasmic CLIC4, p53 and TNF-α showed higher expression in high-risk AC (p < 0.05). As regards the clinical and morphological characteristics of SCCLL, the expression of cytoplasmic CLIC4 was higher in cases presenting lymph node metastasis, cases with more advanced clinical stages or with a high degree of malignancy (p = 0.005, p = 0.029, p <0, 0001). Expression of p53 was higher in highgrade malignant SCCLL (p = 0.001) and TGF-ß decreased significantly as the clinical stage progressed and tumor grade histologically (p <0.05). Increased CLIC4 (in the nucleus, or nucleus and cytoplasm) and TGF-ß, compared to SCCLL (p <0.0001). In contrast, there was an increase in the labeling of cytoplasmic CLIC4 and α-SMA in SCCLL cases, when compared to AC (p <0.0001). In the AC, a negative correlation was observed between nuclear CLIC4 expression and cytoplasmic CLIC4 (r = -0.554, p = <0.0001), and between TGF-ß and α-SMA (r = -0,309; = 0.029). In carcinomas, p53 expression exhibited a positive correlation with TNF-α (r = 0.528, p = 0.0001) and αSMA (r = 0.435, p = 0.002). Our results suggest that a change in CLIC4 cytoplasmic nuclear expression pattern is involved in the process of lip carcinogenesis, accompanied by changes in the expression of p53, TGF-ß, TNF-α and α-SMA, and are related to some of the morphological aspects and clinicians of AC and SCCLL (AU).

Clinicopathological profile and management of 161 cases of actinic cheilitis

AbstractBACKGROUND:Actinic cheilitis (AC) is a potentially malignant disorder of the lip caused by chronic exposure to ultraviolet radiation from the sun.OBJECTIVES:To evaluate the clinical, demographic, morphological and therapeutic management in AC cases data associating to the histopathological grading.METHODS:Demographic, clinical and management data of 161 patients with AC were analyzed. In biopsied cases, two calibrated examiners performed histopathological grading by binary system.RESULTS:There was a prevalence of males (79.5%), aged 40 years or older (77.5%), light-skinned (85.7%), experiencing occupational exposure to sunlight (80.3%), with AC presenting clinically as white lesions (33.6%). Conservative treatment was adopted in 78 cases and biopsy in 83 cases (60.2% graded as low-risk AC). There were no significant associations between histopathological grading and gender (p= 0.509), age (p=0.416), ethnicity (p=0.388), occupational exposure to sunlight (p=1.000) or clinical presentation (p=0.803).CONCLUSION:This study reinforces the hypothesis that demographic and clinical characteristics of AC are not related to histopathological grading. Advice on protection from sun exposure should be encouraged to avoid progression of AC and invasive therapies.

Queilitis glandular / Glandular cheilitis

La queilitis glandular es un proceso muy raro y poco estudiado, donde se observan varios grados de macroquelia (agrandamiento labial) asociada a secreción de saliva espesa en la superficie labial, ocasionando disconfort al paciente. La causa permanece desconocida, pareciendo estar involucrados factores como el daño solar crónico, siendo una enfermedad significativamente más frecuente en personas de piel clara, particularmente en los albinos. Recientemente fueron demostrados alteraciones en la expresión de los canales de transporte del agua en los conductos de las glándulas afectadas por la queilitis glandular, un hecho que puede estar relacionado con la presencia de saliva mucoide espesa que se observa con frecuencia en esta enfermedad. El tratamiento es difícil, obteniéndose mejores resultados después de la exéresis del bermellón labial asociada con disección y remoción cuidadosa de las glándulas salivales menores involucradas.

Elastin accumulation in actinic cheilitis with different degrees of epithelial dysplasia / Acumulación de elastina en queilitis actínica con diferentes grados de displasia epitelial

The extracellular matrix (ECM) plays an important role in the regulation of biological events such as the development of cell migration, proliferation and differentiation. Chronic sun exposure causes changes present in the ECM of actinic cheilitis (AC), a premalignant lesion of the lower lip which helps to understand the carcinogenesis of the lip. This study aimed to investigate elastin, the main component of solar elastosis alternating current in an attempt to establish the relationship between this protein and ECM in epithelial dysplasia. Paraffin embedded tissue sections of the lesions of 35 cases of AC were analyzed by immunohistochemistry for elastin, and became the association with the degree of epithelial dysplasia and age. Highest scores of elastin (+3) was predominant in 45.7 percent of cases of AC, especially in cases of severe dysplasia (n = 3). When comparing the scores of elastin between the different grades of epithelial dysplasia showed no significant difference (P> 0.05, Kruskal-Wallis). This study was not able to demonstrate the influence of elastin on the severity of epithelial dysplasia in AC. Additional studies on other ECM proteins must be conducted in an attempt to better understand the mechanism of malignant progression of the AC.

La matriz extracelular (MEC) juega un papel importante en la regulación de los eventos biológicos, tales como, el desarrollo de la migración celular, proliferación y diferenciación. La exposición solar crónica provoca cambios presentes en la MRC de la queilitis actínica (QA), una lesión premaligna del labio inferior que contribuye a entender la carcinogénesis del labio. Este estudio tuvo como objetivo investigar la elastina, el componente principal de la elastosis solar en corriente alterna en un intento de establecer la relación entre esta proteína y la MEC en displasia epitelial. Se incluyeron en parafina cortes de tejido de las lesiones de 35 casos de QC fueron analizadas mediante técnicas de inmunohistoquímica para elastina, y se hizo la asociación con los grados de displasia epitelial y la edad. La más alta puntuación de la elastina (+3) fue predominante en el 45,7 por ciento de los casos de QA, especialmente en los casos de displasia severa (n = 3). Al comparar las puntuaciones de elastina entre los diferentes grados de displasia epitelial, no mostró diferencia significativa (P> 0,05, Kruskall-Wallis). Este estudio no fue capaz de demostrar la influencia de la elastina sobre gravedad de la displasia epitelial en QA. Estudios adicionales sobre otras proteínas de la MEC deben llevarse a cabo en un intento por comprender mejor el mecanismo de progresión maligna de la QC.

Actinic cheilitis and squamous cell carcinoma of the lip: clinical, histopathological and immunogenetic aspects / Queilite actínica e carcinoma espinocelular do lábio: aspectos clínicos, histopatológicos e imunogenéticos

Actinic cheilitis is the main precancerous lesion of the lip. Squamous cell carcinoma of the lip is reported together with oral carcinomas in the Brazilian official statistics. Overall, they account for 40% of the head and neck carcinomas. In general, physicians and dentists know little about what causes oral tumor development and progression. Tumor suppressor genes and cell proliferation regulatory proteins play a role in the progression of actinic cheilitis to squamous cell carcinoma and in its biological behavior. Knowledge on prognostic and diagnostic markers has a positive impact on the follow-up of these patients.

Queilite actínica é a principal lesão pré-neoplásica do lábio. O carcinoma espinocelular do lábio é incluído nas estatísticas brasileiras junto com os cânceres de boca e, em conjunto, somam 40% dos cânceres de cabeça e pescoço. Há certo desconhecimento médico e odontológico em geral quanto aos fatores relacionados à carcinogênese e à progressão de tumores de boca. Genes de supressão tumoral e proteínas regulatórias de proliferação celular exercem papel na evolução da queilite actínica para carcinoma espinocelular e no comportamento biológico deste. O conhecimento de marcadores de diagnóstico e prognóstico e sua investigação têm utilidade no acompanhamento de tais pacientes.

E-cadherin and c-Met expression in actinic cheilits and lip squamous cell carcinoma

Objective: The aim of this study was to assess epithelial expression of E-cadherin and c-Met in normal lip, in actinic cheilitis and lip squamous cell carcinoma. Study Design: Biopsies of normal lip vermillion (NL, n=18), actinic cheilitis (AC, n=37), and lip SCC (n=22) were processed for E-cadherin and c-Met immunodetection. Epithelial and tumor cell expression was scored for each sample considering staining intensity and percentage. Results: E-cadherin expression was significantly reduced in AC and lip SCC as compared to normal lip (P<0.05), with a significant reduction in lip SCC as compared to AC (P=0.003). Expression of c-Met was significantly higher in AC and lip SCC as compared to NL (P<0.05), with a significant increase in lip SCC as compared to AC (P<0.0001). Conclusion: The results showed that epithelial E-cadherin expression is reduced and c-Met expression is increased as lip carcinogenesis progresses, suggesting that these proteins may be useful markers of malignant transformation.

Morphology of collagen fibers and elastic system fibers in actinic cheilitis.

Background: Actinic cheilitis (AC) is a premalignant condition intimately related to exposure of the lips to sun rays. Aim: The objective of this study was to evaluate the elastic and collagen fibers in the lamina propria of AC. The degree of epithelial atypia was correlated with the quantity of elastic and collagen fibers. Materials and Methods: Fifty-one cases were investigated. One slide was stained with hematoxylin-eosin for the evaluation of atypia, the second was stained with Weigert's resorcin-fuchsin for the assessment of elastic fibers, and the third slide was stained with Mallory's trichrome for the analysis of collagen fibers. Results: Ordinal logistic regression analysis revealed a significant correlation between the presence of atypia and collagen fibers (P<0.05). Conclusions: It was concluded that there seems to be a reduction in the quantity of collagen fibers in cases of moderate and severe atypia. No correlation was observed between the degradation of elastic system fibers and the grade of dysplasia.

Actinic lesions in fishermen's lower lip: clinical, cytopathological and histopathologic analysis

INTRODUCTION: Actinic cheilitis (AC) is considered to be a pre-malignant lesion or an incipient and superficial form of lip squamous cell carcinoma. It is commonly found in individuals whose occupational activities are related to chronic sun exposure and the definitive diagnosis is performed with biopsy. Althoug Exfoliative cytology has been used as a screening procedure to evaluate cancer of the oral cavity no studies have proposed the use of exfoliative cytologic analysis to evaluate and diagnose AC. OBJECTIVE: The purpose of this study was to evaluate lower lip lesions on fishermen related to chronic solar exposure using clinical, cytologic and histopathologic analyses. PATIENTS AND METHODS: Smears taken from the vermilion of the lower lips of 125 fishermen and 30 control individuals were subjected to cytologic analysis. RESULTS: The harvested cells were sufficient for cytologic analysis in 83.2 percent of the samples. Sixteen fishermen exhibited prominent lower lip lesions that justified biopsy and histological studies. In total, 4 specimens were malignant (3.2 percent), and 12 displayed epithelial dysplasia, demonstrating that the prevalence of epithelial dysplasia and malignant lesions was high among the fishermen population. These conditions were strongly associated with infiltration and blurring of the vermilion margin of the lower lip. CONCLUSION: The cytologic analysis was not useful for detecting epithelial dysplasia or malignant alterations.

Queilite actínica crônica, estudo e correlaçães dos aspectos clínicos e histopatológicos / Chronic actinic cheilits, study and correlations between clinical aspects and histopatological findings

A Queilite Actínica crônica (OAC) é uma lesão labial considerada uma das principais lesôes cancerizáveis da boca. Em nosso estudo foram avaliados 29 pacientes portadores de OAC, observando e relacionando a epidemiologia da doença, os aspectos clínicos e histológicos bem como os respectivos graus de atipia celular. A OAC ocorreu em 100% nos indivíduos da raça branca, em 19 homens (65,51%) e 10 mulheres (34,49) e na idade média de 56,14 anos. Foram avaliados também os aspectos clínicos e histológicos da OAC sendo encontrados 14 casos de atipia epitelial discreta (48,27%), 10 casos de atipia epitelial moderada (34,49%) e 5 casos de atipia epitelial severa (17,24%). Através de análise estatística concluímos que clinicamente a presença de áreas leuco- plasicas e o tempo de evolução da lesão superior a cinco anos estão diretamente relacionados aos casos de atipias epiteliais mais graves. O hábito de fumar e de beber parecem contribuir, mas não obtiveram resultados estatisticamente significativos ao aparecimento da 0Ae.

The Chronic Actinic Cheilitis (CAC) is a labial injury considered one of the main precancerous injuries of the mouth. Our study had been evaluated 29 carrying patients of CAC, observing and relating the epidemiology of the illness, clinical and histological aspects as well as the respective degrees of cellular atipia. The CAC occurred in 100% in the individuais of the white race, in 19 men (65.51%) and 10 women (34,49 %) and in the average age of 56,14 years. The clinical and histological aspects of the CAC found had been evaluated also. We found 14 cases of discrete epithelial atipia (48.27%), 10 cases of moderate epithelial atipia (34.49%) and 5 cases of severe epithelial atipia (17.24%). Through statistical analysis we concluded that the presence of leu- coplasics areas and evolution time superior of 5 years are directly related to the cases of more dangerous epithelial atipias. The habit to smoke and drink seems to contribute but they had not gotten statistical significance to the appearance of the CACo.

Queilite angular traumática em eqüinos associada à ingestão de Panicum maximum / Angular cheilitis in horses associated with ingestion of Panicum maximum

Uma condição com aumento da fenda bucal de eqüinos por lesão na comissura labial foi estudada. Este aumento tinha extensão variável e era uni ou bilateral. Na mucosa da bochecha da comissura labial exposta havia pequenas erosões. Durante a mastigação havia perda de pequena quantidade de capim e saliva pela fenda bucal aumentada. Os animais apresentavam bom estado nutricional. O exame histopatológico de tecido retirado da comissura labial revelou epidermite superficial. Nas quatro propriedades onde se verificou o problema, constatou-se que os eqüinos eram mantidos em sistema extensivo de criação em pastagem de Panicum maximum (variedades Tanzânia, Mombaça, Tobiatã e Colonião), com folhas maduras, altas, lignificadas e de bordos cortantes. De acordo com os dados epidemiológicos, com os achados clínicos e histopatológicos, concluí-se que essas lesões foram causadas pela ação cortante das folhas de Panicum maximum, associada à forma de apreensão da pastagem alta e mastigação pelos eqüinos.

A condition with enlargement of the oral cleft in horses was studied. The enlargement of varied extension was uni or bilateral. The cheek mucosa of the labial commissure showed slight erosions. During chewing there was loss of small amounts of grass and saliva through the oral cleft. The affected horses were in good nutritional condition. Histopathological studies of tissues obtained by biopsia, revealed a superficial epidermitis. The pastures consisted of Panicum maximum grass (varieties Tanzânia, Mombaça, Tobiatã and Colonião) which was mature, tall, lignified, with leaves of cutting edges. Based on epidemiological, clinical and histopathological data, it was concluded that the lesions were caused by the hard grass, favored by the way horses pull the tall grass and chew it.

p53 and MDM2 protein expression in actinic cheilitis

Actinic cheilitis is a potentially malignant lip lesion caused by excessive and prolonged exposure to ultraviolet radiation, which can lead to histomorphological alterations indicative of abnormal cell differentiation. In this pathology, varying degrees of epithelial dysplasia may be found. There are few published studies regarding the p53 and MDM2 proteins in actinic cheilitis. Fifty-eight cases diagnosed with actinic cheilitis were histologically evaluated using Banóczy and Csiba (1976) parameters, and were subjected to immunohistochemical analysis using the streptavidin-biotin method in order to assess p53 and MDM2 protein expression. All studied cases expressed p53 proteins in basal and suprabasal layers. In the basal layer, the nuclei testing positive for p53 were stained intensely, while in the suprabasal layer, cells with slightly stained nuclei were predominant. All cases also tested positive for the MDM2 protein, but with varying degrees of nuclear expression and a predominance of slightly stained cells. A statistically significant correlation between the percentage of p53 and MDM2-positive cells was established, regardless of the degree of epithelial dysplasia. The expression of p53 and MDM2 proteins in actinic cheilitis can be an important indicator in lip carcinogenesis, regardless of the degree of epithelial dysplasia.

Comparative analysis of the mast cell density in normal oral mucosa, actinic cheilitis and lip squamous cell carcinoma

Previous studies have shown that the number of mast cells is increased in ultraviolet (UV) irradiated skin and in neoplasias. Actinic cheilitis (AC) is a lesion caused by excessive exposure to sunlight that can transform into lip squamous cell carcinoma. The aim of this study was to compare the number of mast cells in 4 groups: NOM = normal oral mucosa (n=6); MDAC = mild dysplasia in actinic cheilitis (n=13); SDAC = severe dysplasia in actinic cheilitis (n=13); and LSCC = lip squamous cell carcinoma (n=15). The sections were stained by histochemical technique of blue toluidine and visual counting was performed with the aid of a reticulum coupled to the microscope ocular. A calibrated observer performed the count in 5 fields by case at ×400 magnification. The largest mean number of mast cells per group was observed in LSCC (40.1), followed by MDAC (30.5), SDAC (28.6) and NOM (12.2). There were significant differences between NOM and MDAC (p<0.05) and between NOM and LSCC (p<0.05). The increased density of mast cells observed in AC and in LSCC compared to NOM suggests a role for the mast cells in the development of these lesions.

Estudos prévios mostram que os mastócitos estão significantemente aumentados na pele irradiada por ultra-violeta e neoplasias. A queilite actínica (QA) é uma lesão causada por excessiva exposição solar, que pode transformar-se em carcinoma espinocelular de lábio. O objetivo deste estudo foi comparar o número de mastócitos em 4 grupos: MON = mucosa oral normal (n=6); QADL = queilite actínica com displasia leve (n=13); QADS = queilite actínica com displasia severa (n=13); e CECL = carcinoma espinocelular de lábio (n=15). Os cortes foram corados pela técnica histoquímica do azul de toluidina e a contagem visual foi realizada utilizando um retículo acoplado à ocular do microscópio. Um observador calibrado realizou a contagem em 5 campos por caso em magnificação de ×400. A média de mastócitos por grupo foi maior no CECL (40,1), seguida da QADL (30,5), QADS (28,6) e MON (12,2). Houve diferença estatisticamente significante entre MON e QADL (p<0,05) e entre MON e CECL (p<0,05). A maior densidade de mastócitos na QA e no CECL em relação à MON sugere um papel para os mastócitos no desenvolvimento dessas lesões.

Queilite actínica adjacente ao carcinoma espinocelular do lábio como indicador de prognóstico / Actinic cheilitis adjacent to squamous carcinoma of the lips as an indicator of prognosis

Muitos estudos demonstram associação entre queilite actínica e carcinoma espinocelular do lábio. OBJETIVO: Verificar a relação da queilite actínica com o prognóstico dessa neoplasia. MATERIAIS E MÉTODOS: Elaborou-se um estudo de coorte retrospectivo com corte transversal em carcinoma espinocelular do lábio. Cortes histológicos desse tumor, levantados entre 1993-2000, nos arquivos do Departamento de Patologia/Universidade Federal de São Paulo, foram revisados para evidenciar presença ou ausência de queilite actínica no vermelhão adjacente ao tumor. Os prontuários dos pacientes foram revisados à procura de informações sobre exposição solar, metástase e recidiva. A ocorrência ou ausência de recidiva e metástase foi correlacionada com a presença ou ausência de queilite actínica no vermelhão. Os dados obtidos foram analisados pelo teste exato de Fisher. RESULTADOS: Dos 31 pacientes selecionados predominou o sexo masculino, cor da pele branca e localização no lábio inferior. Constatou-se: independência entre a ocorrência de metástase e recidiva com sexo, cor dos pacientes e localizações no lábio superior ou inferior; dependência entre a presença de queilite actínica e elastose solar, dependência entre a ausência de queilite actínica e presença de metástase; independência entre a ausência de queilite actínica e presença de recidiva. CONCLUSÃO: Os tumores originários de queilite actínica têm melhor prognóstico.

Many studies have shown an association between actinic cheilitis and squamous carcinoma of the lips. AIM: The aim of the study was to observe the relation between actinic cheilitis and the prognosis of squamous carcinoma of the lips. MATERIALS AND METHODS This is a retrospective cross-sectional cohort study of squamous carcinoma of the lips. Histological sections of squamous carcinoma tumors done at the the Departament of Pathology of the Sao Paulo Federal University between 1993 and 2000 were reviewed for evidence of actinic cheilitis in the lip vermillion adjacent to the tumor. Patient reports were reviewed to find information about exposure to sun, metastases and relapses. The occurrence or absence of relapses and metastases was correlated with the presence or absence of actinic cheilitis in the lip vermillion. Data was analyzed by FisherÆs Exact test. RESULTS: Of the 31 selected patients, most were caucasian, males and with lower lip involvement. Statistical analysis demonstrated independence between the occurrence of metastases and relapse and gender, skin color and site (lower or upper lips). There was dependence between actinic cheilitis and solar elastosis, and between the absence of actinic cheilitis and the occurrence of metastases. There was no dependence between the absence of actinic cheilitis and the occurrence of relapses. CONCLUSION: It may be concluded that tumors originating from actinic cheilitis have a better prognosis.

Queilite actínica: estudo comparativo entre os achados histopatológicos da biópsia e dos cortes seriados provenientes da vermelhonectomia; estudo de 20 casos / Actinic cheilitis: comparision of microscopic findings on biopsy and on sections of vermilionectomy; a 20 cases study

Vinte casos de queilite actínica com alterações clínicas difusas foram inicialmente submetidos a uma biopsia e posteriormente `a vermelhonectomia. As peças cirúrgicas foram secionadas a cada 3 mm e os achados histopatológicos da biopsia foram comparados aos dos cortes seriados. As alterações epiteliais não ocorreram uniformemente ao longo do vermelhão; a biopsia freqüentemente não representou a área de maior gravidade histológica. Foram detectados focos de carcinoma superficialmente invasivo em áreas descontínuas ao longo do vermelhão em 4 casos. Os achados sugerem que casos de queilite actínica com alterações clínicas difusas possam se tratar de casos mais graves à histopatologia. / Twenty cases of actinic cheilitis with diffuse clinical changes were initially biopsied; a vermilionectomy was then performed. Surgical specimens were sectioned every 3mm; histopathological findings from biopsies were compared with the sections from vermilionectomies. Epithelial changes were not uniform along the vermilion; biopsies did not reveal the most severe area in many cases. Foci of non-continuous areas of superficially invasive carcinoma were detected in 4 cases. These findings suggest that cases of actinic cheilitis presenting with diffuse and poorly demarcated clinical lesions...