Expressão de fatores de proliferação e antiapoptóticos em carcinomas basocelulares
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Data
2016-12-21
Autores
Lima, Jacqueline Silva Brito [UNESP]
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Universidade Estadual Paulista (Unesp)
Resumo
O carcinoma basocelular (CBC) é a neoplasia maligna mais comum entre os homens e sua incidência está aumentando em nosso meio. Pode se manifestar como lesão nodular, superficial, esclerodermiforme, micronodular e fibroepitelioma de Pinkus. O CBC é um carcinoma de baixa mortalidade, porém com elevada morbidade devido ao potencial destrutivo local e às elevadas taxas de reincidência. As diferenças evolutivas dos diversos tipos de carcinomas basocelulares não são bem definidas. A análise de fatores de proliferação e apoptose pode subsidiar o conhecimento sobre a fisiopatologia e as diferenças evolutivas dessas lesões. A literatura revela a escassez de investigações sobre a expressão diferencial de fatores de proliferação (Ki-67) e relacionados à apoptose (p53, survivina e NF-kB-p105) dos diferentes subtipos de carcinomas basocelulares e ainda tumores recidivados. O objetivo desse estudo é avaliar a expressão de marcadores de proliferação celular e apoptose em carcinomas basocelulares dos tipos nodular, superficial, esclerodermiforme e tumores recidivados. Foram selecionados subtipos histológicos únicos, como forma de tentar compreender o comportamento dos CBCs individualmente. As lâminas desses espécimes foram submetidas ao protocolo de marcação imuno-histoquímica. Foram estudadas 100 amostras, sendo 50 unidades de epiderme normal e as demais distribuídas entre cada subtipo tumoral. O padrão de marcação de cada marcador sobre os diferentes tipos de tecidos foi avaliado a partir de modelos lineares generalizados (GLMs) seguidos de teste post-hoc de Sidak, quando necessário. Foram encontradas diferenças estatisticamente significativas (p<0,01) na imunomarcação de diferentes tipos de tecidos para os marcadores Ki-67, p53 e survivina, mas não para o marcador p105 (p=0,21). O marcador Ki-67 foi mais expresso nos esclerodermiformes que em células da epiderme e nos nodulares. A imunomarcação do p53 foi menos expressa na epiderme que nos subtipos superficiais e nas recidivas, e também menos expressa nos esclerodermiformes que em todos os outros subtipos tumorais. A survivina mostrou uma imunomarcação maior na epiderme em relação aos subtipos tumorais estudados. A comparação entre os diferentes marcadores foi avaliada pelo cieficiente de correlação de Spearman, que detectou uma correlação estatisticamente significativa (p<0,01) entre os marcadores, Ki-67 e p53 na imunomarcação dos subtipos estudados e de células da epiderme, e uma correlação entre Ki-67 e survivina quando consideramos apenas as células tumorais. Neste estudo, a expressão simultânea de marcadores permitiu a identificação de padrões de proliferação e apoptose que individualizaram comportamentos em subtipos de CBCs, em consonância com formas recidivadas, e de forma independente na epiderme. Houve diferentes padrões de correlação entre a expressão dos marcadores dos CBCs e da epiderme.
Basal cell carcinoma (BCC) is the most common malignant neoplasm among men and its incidence is increasing in our country. It can manifest as nodular, superficial, sclerodermiform, micronodular and Pinkus fibroepithelioma lesions. BCC is a low-mortality carcinoma, but with high morbidity due to local destructive potential and high rates of recurrence. The evolutionary differences of the various types of basal cell carcinomas are not well defined. The analysis of proliferation and apoptosis factors may support knowledge about the pathophysiology and evolutionary differences of these lesions. The literature reveals the scarcity of investigations on the differential expression of proliferation factors (Ki-67) and related apoptosis (p53, survivin and NF-kB-p105) of the different subtypes of basal cell carcinomas and recurrent tumors. The aim of this study is to evaluate the expression of markers of cell proliferation and apoptosis in basal cell carcinomas of the nodular, superficial, sclerodermiform and recurrent tumors. Unique histological subtypes were selected as a way to attempt to understand the behavior of individual BCCs. The slides of these specimens were submitted to the immunohistochemical labeling protocol. A total of 100 samples were studied, being 50 normal epidermal units and the others distributed between each tumor subtype. The marking pattern of each marker on the different tissue types was evaluated from generalized linear models (GLMs) followed by Sidak post-hoc test, when necessary. Statiscally significant differences (p<0,01) in the immunostaining of different tissue types were found for the Ki-67, p53 and survivin markers, but not for the p105 marker (p=0,21). The Ki-67 marker was more expressed in sclerodermiform than in epidermal and nodular cells. Immunoblotting of p53 was less expressed in the epidermis than in superficial subtypes and relapses, and also less expressed in sclerodermiform than in all other tumor subtypes. Survivin showed a greater immunostaining in the epidermis with respect to the tumor subtypes studied. The comparison between the diferent markers was evaluated by the Spearman correlation coefficient, which detected a statistically significant correlation (p<0,01) between the markers, Ki-67 and p53 in the immunoblotting of the studied subtypes and epidermal cells, and one correlation between Ki-67 and survivin when we considered only tumor cells. In this study, the simultaneous expression of markers allowed the identification of patterns of proliferation and apoptosis that individualized behaviors in subtypes of BCCs, in consonance with relapsed forms, and independently in the epidermis. There were different patterns of correlation between the expression of BCC and epidermal markers.
Basal cell carcinoma (BCC) is the most common malignant neoplasm among men and its incidence is increasing in our country. It can manifest as nodular, superficial, sclerodermiform, micronodular and Pinkus fibroepithelioma lesions. BCC is a low-mortality carcinoma, but with high morbidity due to local destructive potential and high rates of recurrence. The evolutionary differences of the various types of basal cell carcinomas are not well defined. The analysis of proliferation and apoptosis factors may support knowledge about the pathophysiology and evolutionary differences of these lesions. The literature reveals the scarcity of investigations on the differential expression of proliferation factors (Ki-67) and related apoptosis (p53, survivin and NF-kB-p105) of the different subtypes of basal cell carcinomas and recurrent tumors. The aim of this study is to evaluate the expression of markers of cell proliferation and apoptosis in basal cell carcinomas of the nodular, superficial, sclerodermiform and recurrent tumors. Unique histological subtypes were selected as a way to attempt to understand the behavior of individual BCCs. The slides of these specimens were submitted to the immunohistochemical labeling protocol. A total of 100 samples were studied, being 50 normal epidermal units and the others distributed between each tumor subtype. The marking pattern of each marker on the different tissue types was evaluated from generalized linear models (GLMs) followed by Sidak post-hoc test, when necessary. Statiscally significant differences (p<0,01) in the immunostaining of different tissue types were found for the Ki-67, p53 and survivin markers, but not for the p105 marker (p=0,21). The Ki-67 marker was more expressed in sclerodermiform than in epidermal and nodular cells. Immunoblotting of p53 was less expressed in the epidermis than in superficial subtypes and relapses, and also less expressed in sclerodermiform than in all other tumor subtypes. Survivin showed a greater immunostaining in the epidermis with respect to the tumor subtypes studied. The comparison between the diferent markers was evaluated by the Spearman correlation coefficient, which detected a statistically significant correlation (p<0,01) between the markers, Ki-67 and p53 in the immunoblotting of the studied subtypes and epidermal cells, and one correlation between Ki-67 and survivin when we considered only tumor cells. In this study, the simultaneous expression of markers allowed the identification of patterns of proliferation and apoptosis that individualized behaviors in subtypes of BCCs, in consonance with relapsed forms, and independently in the epidermis. There were different patterns of correlation between the expression of BCC and epidermal markers.
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Palavras-chave
Carcinoma basocelular, Apoptose, Proliferação, Neoplasia, Basal cell carcinoma, Apoptosis, Proliferation, Neoplasm