Expressão de calreticulina em neoplasias malignas e desordens potencialmente malignas
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Data
2022-02-14
Autores
Palaçon, Mariana Paravani
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Editor
Universidade Estadual Paulista (Unesp)
Resumo
Dentre as neoplasias que acometem a cavidade oral, 95% delas são diagnosticadas como carcinoma espinocelular e muitas vezes, estes tumores são precedidos por alterações clínicas que apresentam uma taxa de transformação maligna, chamadas de desordens potencialmente malignas orais (DPMOs). Dentre elas, a mais comum é a leucoplasia oral (LO) que é definida como ‘’uma placa branca de risco questionável definida após a exclusão de outras doenças ou distúrbios conhecidos que mimetizam este aspecto, mas que não carregam nenhum risco conhecido para o câncer’’, e sua taxa de transformação maligna de 0,3 a 13,8%. A leucoplasia verrucosa proliferativa (LVP) é caracterizada por múltiplas placas brancas que apresentam um comportamento clínico persistente e progressivo para malignidade, sendo a sua taxa de transformação maligna de 70%. A calreticulina (CRT) é uma proteína multifuncional que pode apresentar propriedades anti-oncogênicas e oncogênicas. Apesar de seu mecanismo em neoplasias da cavidade oral não ser bem elucidado, existem estudos que mostram que a expressão elevada da CRT está relacionada com um prognóstico desfavorável da doença. Contudo, ainda não existem trabalhos que avaliam a expressão de CRT em DPMOs. Desta forma, o presente trabalho teve como objetivos específicos: (1) realizar uma revisão sistemática da literatura com intuito de avaliar a expressão de CRT e o seu valor prognóstico em pacientes com diferentes tipos de carcinomas; (2) avaliar a expressão imuno-histoquímica de CRT em DMPOs; (3) avaliar a expressão gênica de CRT em DPMOs. Na revisão sistemática foram encontrados 2100 artigos, mas somente 13 estavam dentro dos critérios de inclusão do nosso trabalho. Na meta-análise obtivemos uma diferença estatística significativa em que homens apresentam 2.13 vezes mais chances de apresentar alta expressão de CRT. Na análise imuno-histoquímica foram utilizadas 190 amostras parafinadas adquiridas através de biopsias de pacientes com diagnostico clínico-patológico de LO, LVP, e hiperplasia fibrosa inflamatória (HFI). As amostras foram avaliadas segundo a intensidade de marcação na qual apresentou um aumento na expressão de CRT no grupo LVP em relação ao grupo LO. Na analise da expressão genica da CRT realizou-se por meio da técnica de reação de PCR quantitativo em tempo real. Neste experimento foram utilizados fragmentos de tecidos lesionais congelados de pacientes com diagnóstico clínico-patológico de HFI, LO, LVP no qual revelou uma modulação na expressão de CRT, na qual houve uma redução na expressão no grupo LO quando comparado ao grupo HFI e um aumento da expressão de CRT no grupo LVP quando comparado ao grupo LO. Com os nossos resultados concluímos que há uma superexpressão de CRT na LVP e que este achado pode estar correlacionado com o sua alta taxa de transformação maligna.
ABSTRACT The neoplasms that affect the oral cavity 95% of them are diagnosed as squamous cell carcinoma and these tumors are often preceded by clinical changes that present a rate of malignant transformation, called potentially malignant oral disorders (OPMDs). Among them, the most common is oral leukoplakia (OL) which is defined as ''a white plaque of questionable risk defined after excluding other known diseases or disorders that mimic this aspect but carry no known risk for cancer. '', and its malignant transformation rate from 0.3 to 13.8%. Proliferative verrucous leukoplakia (PVL) is characterized by multiple white plaques that present a persistent and progressive clinical behavior towards malignancy, with a malignant transformation rate of 70%. In the early phases of LVP, it can clinically and histopathologically mimic other DPMOs, such as oral lichen planus and/or oral lichenoid lesions. Calreticulin (CRT) is a multifunctional protein that may have anti-oncogenic and oncogenic properties. Although its mechanism in oral cavity neoplasms is not so well elucidated, there are studies that show that the high expression of CRT is related to a poor prognosis of the disease. However, there are still no works evaluating the expression of CRT in OPMDs. Thus, the present study had the following specific objectives: (1) to carry out a systematic review of the literature in order to evaluate the expression of CRT and its prognostic value in patients with different types of carcinomas; (2) to evaluate the immunohistochemical expression of CRT in OPMDs; (3) to evaluate CRT gene expression in OPMDs. In the systematic review, 2100 articles were found, but only 13 were within the inclusion criteria of our work. In the meta-analysis, we obtained a statistically significant difference in that men are 2.13 times more likely to have high CRT expression. In the immunohistochemical analysis, 190 paraffin samples acquired through biopsies of patients with clinicopathological diagnosis of LO, PVL, and inflammatory fibrous hyperplasia (HFI) were used. The samples were evaluated according to the labeling intensity which showed an increase in CRT expression in the LVP group compared to the LO group. The analysis of CRT gene expression was performed using the technique of real-time quantitative PCR reaction. In this experiment, fragments of frozen lesional tissues from patients with clinical-pathological diagnosis of HFI, LO, LVP were used, which revealed a modulation in the expression of CRT, in which there was a reduction in expression in the LO group when compared to the HFI group and an increase of CRT expression in the LVP group when compared to the LO group. With our results, we conclude that there is an overexpression of CRT in LVP and that this finding may be correlated with its high rate of malignant transformation.
ABSTRACT The neoplasms that affect the oral cavity 95% of them are diagnosed as squamous cell carcinoma and these tumors are often preceded by clinical changes that present a rate of malignant transformation, called potentially malignant oral disorders (OPMDs). Among them, the most common is oral leukoplakia (OL) which is defined as ''a white plaque of questionable risk defined after excluding other known diseases or disorders that mimic this aspect but carry no known risk for cancer. '', and its malignant transformation rate from 0.3 to 13.8%. Proliferative verrucous leukoplakia (PVL) is characterized by multiple white plaques that present a persistent and progressive clinical behavior towards malignancy, with a malignant transformation rate of 70%. In the early phases of LVP, it can clinically and histopathologically mimic other DPMOs, such as oral lichen planus and/or oral lichenoid lesions. Calreticulin (CRT) is a multifunctional protein that may have anti-oncogenic and oncogenic properties. Although its mechanism in oral cavity neoplasms is not so well elucidated, there are studies that show that the high expression of CRT is related to a poor prognosis of the disease. However, there are still no works evaluating the expression of CRT in OPMDs. Thus, the present study had the following specific objectives: (1) to carry out a systematic review of the literature in order to evaluate the expression of CRT and its prognostic value in patients with different types of carcinomas; (2) to evaluate the immunohistochemical expression of CRT in OPMDs; (3) to evaluate CRT gene expression in OPMDs. In the systematic review, 2100 articles were found, but only 13 were within the inclusion criteria of our work. In the meta-analysis, we obtained a statistically significant difference in that men are 2.13 times more likely to have high CRT expression. In the immunohistochemical analysis, 190 paraffin samples acquired through biopsies of patients with clinicopathological diagnosis of LO, PVL, and inflammatory fibrous hyperplasia (HFI) were used. The samples were evaluated according to the labeling intensity which showed an increase in CRT expression in the LVP group compared to the LO group. The analysis of CRT gene expression was performed using the technique of real-time quantitative PCR reaction. In this experiment, fragments of frozen lesional tissues from patients with clinical-pathological diagnosis of HFI, LO, LVP were used, which revealed a modulation in the expression of CRT, in which there was a reduction in expression in the LO group when compared to the HFI group and an increase of CRT expression in the LVP group when compared to the LO group. With our results, we conclude that there is an overexpression of CRT in LVP and that this finding may be correlated with its high rate of malignant transformation.
Descrição
Palavras-chave
Leucoplasia oral, Calreticulina, Imuno-histoquímica, Reação em cadeia da polimerase em tempo real, Leukoplakia oral, Calreticulin, Immunohistochemistry, Real-time polymerase chain reaction