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Instabilidade de microssatélites como fator preditivo de resposta à quimioterapia perioperatória no adenocarcinoma gástrico e da junção gastroesofágica
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Introdução: Apesar de o gold standard nos doentes com adenocarcinoma gástrico e da junção gastroesofágica (JGE) localmente avançado ser a quimioterapia (QT) perioperatória, há uma evidência crescente, mas ainda incipiente, de que a instabilidade de microssatélites (MSI), caracterizada por expressão defeituosa de proteínas do sistema de mismatch repair (MMR), pode constituir um fator de prognóstico favorável, mas um fator preditivo negativo de resposta à QT. Objetivos: Definiu-se como objetivo primário avaliar o grau de regressão tumoral (GRT) nos doentes com adenocarcinoma gástrico ou da JGE localmente avançado, estratificando por status de MSI. Os objetivos específicos são: 1) estimar a prevalência de MSI em amostras tumorais dos doentes; 2) avaliar o GRT a regimes de QT perioperatória diferentes (FLOT vs ECF), estratificando por status de MSI; 3) avaliar a sobrevivência livre de progressão (SLP) e a sobrevivência global (SG), estratificando por status de MSI. Métodos: Estudo observacional de coorte retrospetivo unicêntrico, com recolha de dados clínicos e avaliação da MSI por métodos imunohistoquímicos e do GRT. Resultados: Verificou-se que 40,5% dos tumores apresentavam uma expressão defeituosa das proteínas de MMR (dMMR). Em comparação com os tumores com MMR preservado (pMMR), os dMMR apresentaram de forma estatisticamente significativa (p=0,024) uma pior regressão tumoral após QT pré-operatória. Não se atingiu a SG e SLP medianas em nenhum dos grupos (pMMR e dMMR). Apesar de não se ter verificado uma diferença estatisticamente significativa entre as curvas dos tumores pMMR e dMMR tanto na SG (p=0,603) como na SLP (p=0,917), a SG a 5 anos foi de 75,0% nos tumores dMMR e de 57,5% nos tumores pMMR. O esquema de QT utilizado não influenciou o GRT, a SG e a SLP. Conclusões: Nesta população, os tumores dMMR parecem ter pior resposta à QT préoperatória e não parecem um prognóstico diferente comparativamente com os tumores pMMR.
Background: Although the gold standard in patients with locally advanced gastric and gastroesophageal junction (GEJ) adenocarcinoma is perioperative chemotherapy, there is growing but still incipient evidence that microsatellite instability (MSI), characterized by defective expression of proteins of the mismatch repair system (MMR), may constitute a favorable prognostic factor but a negative predictor of chemotherapy response. Objectives: The primary objective was to assess the tumor regression grading (TRG) in patients with locally advanced gastric or GEJ adenocarcinoma, stratified by MSI status. The specific objectives are: 1) to estimate the prevalence of MSI in tumor samples from patients; 2) assess TRG at different perioperative chemotherapy regimens (FLOT vs ECF), stratified by MSI status; 3) assess progression-free survival (PFS) and overall survival (OS), stratifying by MSI status. Methods: Observational, unicentric, retrospective cohort study, with clinical data collection and evaluation of MSI by immunohistochemical methods and TRG. Results: The defective expression of the MMR proteins (dMMR) was found in 40,5% of the tumors. Compared with tumors with preserved MMR (pMMR), dMMR showed a statistically significant (p=0,024) worse tumor regression after preoperative chemotherapy. Median OS and PFS were not reached in neither group (pMMR and dMMR). Although there was no statistically significant difference between the curves of pMMR and dMMR tumors in both OS (p=0,603) and PFS (p=0,917), OS at 5 years was 75,0% in dMMR and 57,5% in pMMR cancers. The chemotherapy regimen used did not influence TRG, OS and PFS. Conclusions: In this population, dMMR tumors seem to have a worse response to preoperative QT and do not seem to have a different prognosis compared to pMMR tumors.
Background: Although the gold standard in patients with locally advanced gastric and gastroesophageal junction (GEJ) adenocarcinoma is perioperative chemotherapy, there is growing but still incipient evidence that microsatellite instability (MSI), characterized by defective expression of proteins of the mismatch repair system (MMR), may constitute a favorable prognostic factor but a negative predictor of chemotherapy response. Objectives: The primary objective was to assess the tumor regression grading (TRG) in patients with locally advanced gastric or GEJ adenocarcinoma, stratified by MSI status. The specific objectives are: 1) to estimate the prevalence of MSI in tumor samples from patients; 2) assess TRG at different perioperative chemotherapy regimens (FLOT vs ECF), stratified by MSI status; 3) assess progression-free survival (PFS) and overall survival (OS), stratifying by MSI status. Methods: Observational, unicentric, retrospective cohort study, with clinical data collection and evaluation of MSI by immunohistochemical methods and TRG. Results: The defective expression of the MMR proteins (dMMR) was found in 40,5% of the tumors. Compared with tumors with preserved MMR (pMMR), dMMR showed a statistically significant (p=0,024) worse tumor regression after preoperative chemotherapy. Median OS and PFS were not reached in neither group (pMMR and dMMR). Although there was no statistically significant difference between the curves of pMMR and dMMR tumors in both OS (p=0,603) and PFS (p=0,917), OS at 5 years was 75,0% in dMMR and 57,5% in pMMR cancers. The chemotherapy regimen used did not influence TRG, OS and PFS. Conclusions: In this population, dMMR tumors seem to have a worse response to preoperative QT and do not seem to have a different prognosis compared to pMMR tumors.
Descrição
Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2022
Palavras-chave
Instabilidade de microssatélites Adenocarcinoma gástrico Adenocarcinoma da junção gastroesofágica Quimioterapia perioperatória Oncologia