Imunoexpressão das proteínas DEK e Fosfo-P38 em tecidos tumorais de câncer de reto pré tratamento neoadjuvante
Arquivos
Data
2021-09-30
Autores
Tadokoro, Rebeca de Barros [UNIFESP]
Orientadores
Forones, Nora Manoukian [UNIFESP]
Tipo
Dissertação de mestrado
Título da Revista
ISSN da Revista
Título de Volume
Resumo
Introdução: O câncer colorretal (CCR), é mundialmente a terceira causa de câncer, e aproximadamente um quarto dos CCRs está localizado no reto, representando entre 27% e 58% de CCR. Segundo estudos o proto-oncogene DEK (D6S231E), envolvido em vários processos nucleares, pode acelerar a tumorigênese e a progressão neoplásica. A imunoexpressão da proteína DEK vem sendo estudada como possível marcador preditivo de agressividade, resposta patológica e prognóstico, não só no adenocarcinoma retal, mas também em outros tipos de tumores. Além disso, outra associação direta que vêm sendo estudada é a superexpressão de DEK à proteína em sua forma ativa Fosfo-P38, um fator importante relacionado eventos apoptóticos. Objetivos: Avaliar a imunoexpressão das proteínas DEK e Fosfo-P38 antes da quimio e radioterapia neoadjuvante em pacientes com adenocarcinoma de reto, e correlacionar a expressão destes marcadores com a resposta terapêutica, resposta clínica e sobrevida. Casuística e Método: Analisamos pacientes com adenocarcinoma de reto médio e baixo ao diagnóstico que foram submetidos a quimio e radioterapia, seguida de ressecção cirúrgica do tumor. Foi estudada a expressão e quantificação dos marcadores DEK e Fosfo-P38, por meio do método imunohistoquímico (IHQ) nos tecidos de biópsia do tumor ao diagnóstico aplicado o sistema HScore (análise semiquantitativa), baseado na intensidade da reação x na extensão da marcação (%). As reações com escore ≥4 foram consideradas positivas e as com escore <4, negativas. Resultados: Foram incluidos 22 pacientes. A média de idade foi de 63,55 anos (DP: ± 13,49), com predominância do sexo feminino (63,60%). Com relação as características relativas ao tumor, a maioria (77,3%) apresentou um tumor com tamanho menor ou igual a 4cm com predominância de tumores moderadamente diferenciados (81,8%). 59,2% dos casos foram submetidos a amputação abdominoperineal e metade dos pacientes fizeram quimioterapia adjuvante. Com relação ao desfecho, 50% não apresentavam sinais de recorrência, 18,2% apresentavam recorrência e 31,8% dos pacientes tinham falecido. Com relação ao estádio clínico pré-operatório, 72,7% dos pacientes eram T3; 18,2% T4; 31,8% eram N1 e 50% N0. Nenhum dos casos apresentava metástase a distância. Após a neoadjuvância 54,6% eram T3 e 13,6% T0. Em relação aos marcadores teciduais estudados 22,7% dos casos foram positivos para DEK e 63,6% positivos para Fosfo-P38. Houve correlação positiva entre a imunoexpressão da proteína DEK e o estádio TNM (pós neoadjuvância), apresentando um p=0,011. Não houve correlação entre a imunoexpressão da proteína Fosfo-P38 e o estádio TNM clínico ou patológico. Observamos maior sobrevida em pacientes com HScore Negativo (<4), com média de 141,33 meses (IC 95%: 112,41- 170,25), quando comparado a pacientes que apresetaram HScore Positivo (≥4) com média de 25,10 meses (IC 95%:17,36-32,84) (p< 0,001). Conclusões: A maior expressão da proteína DEK apresentou correlação positiva com o TNM da peça cirúrgica, isto é, quanto maior a expressão de DEK, mais avançado o estádio. Pacientes que apresentaram a expressão de DEK <4 tiveram maior sobrevida.
Introduction: Colorectal cancer (CCR) is the third leading cause of cancer worldwide, and approximately a quarter of CCRs are located in the rectum, representing between 27% and 58% of CCR. According to studies, the DEK proto-oncogene (D6S231E), involved in several nuclear processes, can accelerate tumorigenesis and neoplastic progression. The immunoexpression of DEK protein has been studied as a possible predictive marker of aggressiveness, pathological response and prognosis, not only in rectal adenocarcinoma, but also in other types of tumors. Furthermore, another direct association that has been studied is the overexpression of DEK to the protein in its active form phosphoP38, an important factor related to apoptotic events. Objectives: To evaluate the immunoexpression of DEK and phospho-P38 proteins before neoadjuvant chemotherapy and radiotherapy in patients with adenocarcinoma of the rectum, and to correlate the expression of these markers with therapeutic response, clinical response and survival. Material and Method: We analyzed patients with adenocarcinoma of the middle and low rectum at diagnosis who underwent chemotherapy and radiotherapy, followed by surgical resection of the tumor. The expression and quantification of DEK and phospho-P38 markers was studied using the immunohistochemical method (IHC) in the tissue of tumor biopsy at the diagnosis applied to the HScore system (semiquantitative analysis), based on the intensity of the reaction x on the extent of the marking (%). Reactions with a score ≥4 were considered positive and those with a score <4, negative. Results: 22 patients were included. The mean age was 63.55 years (SD: ± 13.49), with a predominance of females (63.60%). Regarding the characteristics related to the tumor, the majority (77.3%) had a tumor with a size less than or equal to 4cm, with a predominance of moderately differentiated tumors (81.8%). 59.2% of the cases underwent abdominoperineal amputation and half of the patients underwent adjuvant chemotherapy. Regarding the outcome, 50% had no signs of recurrence, 18.2% had recurrence and 31.8% of the patients had died. Regarding the preoperative clinical stage, 72.7% of patients were T3; 18.2% T4; 31.8% were N1 and 50% N0. None of the cases had distant metastasis. After neoadjuvant therapy, 54.6% were T3 and 13.6% were T0. Regarding the tissue markers studied, 22.7% of the cases were positive for DEK and 63.6% positive for phospho-P38. There was a positive correlation between DEK protein immunoexpression and TNM stage (post neoadjuvant), with p=0.011. There was no correlation between phospho-P38 protein immunoexpression and clinical or pathological TNM stage. We observed greater survival in patients with a Negative HSscore (<4), with a mean of 141.33 months (95% CI: 112.41-170.25), when compared to patients who had a Positive HSscore (≥4) with a mean of 25 .10 months (95% CI: 17.36-32.84) (p<0.001). Conclusions: The higher expression of DEK protein was positively correlated with the TNM of the surgical specimen, that is, the greater the expression of DEK, the more advanced the stage. Patients who presented DEK expression <4 had longer survival.
Introduction: Colorectal cancer (CCR) is the third leading cause of cancer worldwide, and approximately a quarter of CCRs are located in the rectum, representing between 27% and 58% of CCR. According to studies, the DEK proto-oncogene (D6S231E), involved in several nuclear processes, can accelerate tumorigenesis and neoplastic progression. The immunoexpression of DEK protein has been studied as a possible predictive marker of aggressiveness, pathological response and prognosis, not only in rectal adenocarcinoma, but also in other types of tumors. Furthermore, another direct association that has been studied is the overexpression of DEK to the protein in its active form phosphoP38, an important factor related to apoptotic events. Objectives: To evaluate the immunoexpression of DEK and phospho-P38 proteins before neoadjuvant chemotherapy and radiotherapy in patients with adenocarcinoma of the rectum, and to correlate the expression of these markers with therapeutic response, clinical response and survival. Material and Method: We analyzed patients with adenocarcinoma of the middle and low rectum at diagnosis who underwent chemotherapy and radiotherapy, followed by surgical resection of the tumor. The expression and quantification of DEK and phospho-P38 markers was studied using the immunohistochemical method (IHC) in the tissue of tumor biopsy at the diagnosis applied to the HScore system (semiquantitative analysis), based on the intensity of the reaction x on the extent of the marking (%). Reactions with a score ≥4 were considered positive and those with a score <4, negative. Results: 22 patients were included. The mean age was 63.55 years (SD: ± 13.49), with a predominance of females (63.60%). Regarding the characteristics related to the tumor, the majority (77.3%) had a tumor with a size less than or equal to 4cm, with a predominance of moderately differentiated tumors (81.8%). 59.2% of the cases underwent abdominoperineal amputation and half of the patients underwent adjuvant chemotherapy. Regarding the outcome, 50% had no signs of recurrence, 18.2% had recurrence and 31.8% of the patients had died. Regarding the preoperative clinical stage, 72.7% of patients were T3; 18.2% T4; 31.8% were N1 and 50% N0. None of the cases had distant metastasis. After neoadjuvant therapy, 54.6% were T3 and 13.6% were T0. Regarding the tissue markers studied, 22.7% of the cases were positive for DEK and 63.6% positive for phospho-P38. There was a positive correlation between DEK protein immunoexpression and TNM stage (post neoadjuvant), with p=0.011. There was no correlation between phospho-P38 protein immunoexpression and clinical or pathological TNM stage. We observed greater survival in patients with a Negative HSscore (<4), with a mean of 141.33 months (95% CI: 112.41-170.25), when compared to patients who had a Positive HSscore (≥4) with a mean of 25 .10 months (95% CI: 17.36-32.84) (p<0.001). Conclusions: The higher expression of DEK protein was positively correlated with the TNM of the surgical specimen, that is, the greater the expression of DEK, the more advanced the stage. Patients who presented DEK expression <4 had longer survival.
Descrição
Citação
TADOKORO, R. B. Imunoexpressão das proteínas DEK e Fosfo-P38 em tecidos tumorais de câncer de reto pré tratamento neoadjuvante. 2021. 92 f. Dissertação (Mestrado em Medicina Translacional) – Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, 2021.