Perfil de marcadores pronóstico en pacientes con carcinoma escamocelular de lengua, tratados en el Instituto de Cancerología Clínica Las Américas en la ciudad de Medellín, en el período 2008 a 2017.
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Data
2020-08-31
Autores
Colonia García, Adriana Milena
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Universidade Estadual Paulista (Unesp)
Resumo
O carcinoma espinocelular de língua (OTSCC) é a neoplasia maligna mais comum encontrada na cavidade oral. As características biológicas das células tumorais não foram incluídas no sistema de classificação Tumor, Nódulo, Metástase (TNM), a mais usada atualmente para determinar o prognóstico. O conhecimento da expressão de biomarcadores, características clínicas e histopatológicas auxiliaria na identificação dos grupos de risco, permitindo a personalização do tratamento, melhorando as chances de sobrevivência. Objetivo. Explorar a relação entre a expressão de biomarcadores (Ki-67, E-cadherin, MMP-9 e α-SMA), as características sociodemográficas, clínicas e histopatológicas com a sobrevida de pacientes com OTSCC. Materiais e métodos. Foram incluídos pacientes com OTSCC do Instituto de Cancerologia Clínica Las Américas, na cidade de Medellín, de 2008 a 2017. As características demográficas, clínicas e patológicas foram obtidas das fichas clínicas e registradas, e as amostras foram submetidas a reações imuno-histoquímicas com os anticorpos S100, Ki-67, E-cadherin, α-SMA e MMP-9. A influência dessas características na sobrevida específica da doença (DSS) foi analisada pelo método de Kaplan-Meier e pelo modelo de riscos proporcionais de Cox. Resultados. Oitenta pacientes foram elegíveis para o estudo, dos quais 55% eram do sexo masculino. A idade média dos pacientes foi de 63,1 ± 16 anos. 63,5% dos OTSCC foram bem diferenciados e 58,8% foram diagnosticados em estádios avançados. Invasão linfovascular (LVI α-SMA+) e perineural (PNI S100+) foram detectados em 60% e 75% dos OTSCC, respectivamente. A presença simultânea de LVI e PNI esteve associada ao estádio clínico avançado, linfonodos positivos e ao prognóstico desfavorável do OTSCC (p<0,05). O seguimento médio foi de 26,4 ± 25 meses, o tempo médio de sobrevida do diagnóstico foi de 62,2 ± 7,8 meses (IC 95%; 46,9; 77,5) e a porcentagem de DSS em 5 anos foi de 41%. Na análise univariada, o DSS em 5 anos foi influenciado por estar sem companheiro (HR = 0,62; p=0,030), estádio avançado (HR = 5,37; p<0,001), recebeu glossectomia total (HR = 7,06; p=0,011), localização na língua móvel (HR = 0,44; p=0,019), tumor ≥3 cm (HR = 3,42; p=0,001), margens cirúrgicas comprometidas (HR = 2,04; p=0,041), metástase linfonodal (HR = 3,07; p=0,002) e tumor pouco diferenciado (HR = 3,67; p=0,019). O DSS não foi influenciado pela expressão de nenhum dos anticorpos avaliados. A análise multivariada mostrou que estádio clínico avançado (HR = 5,29; p<0,001), localização na língua móvel (HR = 0,34; p=0,004) e tumor pouco diferenciado (HR = 3,8; p=0,020) são preditores independentes para DSS. Conclusão. Não foi possível estabelecer a correlação prognóstica entre Ki-67, E-cadherin, MMP-9 e α-SMA e a sobrevida dos pacientes com OTSCC. A localização do carcinoma espinocelular na base da língua, tumor superior a 3 cm e pouco diferenciado, foram fatores independentes que correlacionaram-se com a sobrevida. A presença de LVI e PNI, identificada com precisão por imuno-histoquímica, deve ser avaliada no futuro para estabelecer sua utilidade clínica.
Oral Tongue Squamous Cell Carcinoma (OTSCC) is the most common malignancy found in the oral cavity. The current prognosis-associated tumor classification system (Tumor, Nodule, Metastasis – TNM) did not include the tumor cell biological biomarkers. Knowledge of biomarkers expression, clinical and histopathological characteristics have the potential to improve the identification and differentiation of risk groups and individualized the cancer treatment to increase the overall survival. Objective. The aim of this study was to analyze the correlation of the expression of Ki-67, E-cadherin, MMP-9 and α-SMA, and, the sociodemographic, clinical, and histopathological characteristics with survival of patients with OTSCC. Material and methods. OTSCC patients from the Cancerology Institute Clínica Las Américas, in the city of Medellin, from 2008 to 2017 were included. The retrospective analysis includes demographic, clinical and pathological data, and the tissue samples underwent immunohistochemical analysis of S100, Ki-67, E-cadherin, α-SMA, and MMP-9 markers. The statistical analysis was performed using the Kaplan-Meier method and Cox proportional hazards model and the outcome assessed was disease specific survival (DSS). Results. Eighty eligible patients were included in the study. Higher male prevalence (55%) was observed. The mean age was 63,1±16 years, 63,5% of OTSCC were well-differentiated tumors and 58.8% were detected in advanced stages. Lymphovascular invasion (LVI α-SMA+) and perineural invasion (PNI S100+) were detected in 60% and 75% of OTSCC, respectively. The presence of concomitant LVI and PNI was associated with the advanced clinical stage, metastatic nodes, and poor prognosis of OTSCC (p<0.05). The OTSCC 5-years disease-specific survival rate was 41% with a mean of 62,2±7,8 months (IC 95%; 46,9; 77,5) of follow-up. According to the univariate analysis, DSS was affected by the single marital status (HR=0,62; p=0.030), tumors with an advanced clinical stage (HR=5,37; p<0,001), total glossectomy treatment (HR=7,06; p=0.011), tumors arising from mobile part of the tongue (HR=0,44; p=0.019), tumor size ≥3 cm (HR=3,42; p=0.001), compromised surgical margins (HR=2,04; p=0.041), lymph node metastasis (HR=3,07; p=0.002), and undifferentiated tumor (HR=3,67; p=0.019). However, the expression of biomarkers Ki-67, E-cadherin, α-SMA, and MMP-9, showed no correlation with DSS. On the other hand, the multivariate analysis demonstrated that tumors with advanced clinical stage (HR=5,29; p<0,001), tumors arising from mobile tongue region (HR=0,34; p=0.004), and undifferentiated tumor (HR=3,8; p=0.020) are independent predictors for DSS. Conclusion. The biomarkers Ki-67, E-cadherin, MMP-9 and α-SMA, did not show correlation with survival or prognosis in our sample. Base of tongue arising tumors, tumors larger than 3 cm and undifferentiated tumors were independent factors that affected survival (DSS) rate. The simultaneous presence of LVI and PNI, accurately identified by immunohistochemistry, demonstrated potential to influence the survival rate through rapid diagnosis and should be evaluated in the future to establish their clinical utility.
Oral Tongue Squamous Cell Carcinoma (OTSCC) is the most common malignancy found in the oral cavity. The current prognosis-associated tumor classification system (Tumor, Nodule, Metastasis – TNM) did not include the tumor cell biological biomarkers. Knowledge of biomarkers expression, clinical and histopathological characteristics have the potential to improve the identification and differentiation of risk groups and individualized the cancer treatment to increase the overall survival. Objective. The aim of this study was to analyze the correlation of the expression of Ki-67, E-cadherin, MMP-9 and α-SMA, and, the sociodemographic, clinical, and histopathological characteristics with survival of patients with OTSCC. Material and methods. OTSCC patients from the Cancerology Institute Clínica Las Américas, in the city of Medellin, from 2008 to 2017 were included. The retrospective analysis includes demographic, clinical and pathological data, and the tissue samples underwent immunohistochemical analysis of S100, Ki-67, E-cadherin, α-SMA, and MMP-9 markers. The statistical analysis was performed using the Kaplan-Meier method and Cox proportional hazards model and the outcome assessed was disease specific survival (DSS). Results. Eighty eligible patients were included in the study. Higher male prevalence (55%) was observed. The mean age was 63,1±16 years, 63,5% of OTSCC were well-differentiated tumors and 58.8% were detected in advanced stages. Lymphovascular invasion (LVI α-SMA+) and perineural invasion (PNI S100+) were detected in 60% and 75% of OTSCC, respectively. The presence of concomitant LVI and PNI was associated with the advanced clinical stage, metastatic nodes, and poor prognosis of OTSCC (p<0.05). The OTSCC 5-years disease-specific survival rate was 41% with a mean of 62,2±7,8 months (IC 95%; 46,9; 77,5) of follow-up. According to the univariate analysis, DSS was affected by the single marital status (HR=0,62; p=0.030), tumors with an advanced clinical stage (HR=5,37; p<0,001), total glossectomy treatment (HR=7,06; p=0.011), tumors arising from mobile part of the tongue (HR=0,44; p=0.019), tumor size ≥3 cm (HR=3,42; p=0.001), compromised surgical margins (HR=2,04; p=0.041), lymph node metastasis (HR=3,07; p=0.002), and undifferentiated tumor (HR=3,67; p=0.019). However, the expression of biomarkers Ki-67, E-cadherin, α-SMA, and MMP-9, showed no correlation with DSS. On the other hand, the multivariate analysis demonstrated that tumors with advanced clinical stage (HR=5,29; p<0,001), tumors arising from mobile tongue region (HR=0,34; p=0.004), and undifferentiated tumor (HR=3,8; p=0.020) are independent predictors for DSS. Conclusion. The biomarkers Ki-67, E-cadherin, MMP-9 and α-SMA, did not show correlation with survival or prognosis in our sample. Base of tongue arising tumors, tumors larger than 3 cm and undifferentiated tumors were independent factors that affected survival (DSS) rate. The simultaneous presence of LVI and PNI, accurately identified by immunohistochemistry, demonstrated potential to influence the survival rate through rapid diagnosis and should be evaluated in the future to establish their clinical utility.
Descrição
Palavras-chave
Neoplasias de la lengua, Carcinoma de células escamosas, Pronóstico, Biomarcadores, Tasa de supervivencia, Tongue neoplasms, Squamous cell carcinoma, Prognostic factors, Biomarkers, Survival rate