Marina Alessandra Pereira1,2, Marcus Fernando Kodama Pertille Ramos3,4, André Roncon Dias3,4, Sheila Friedrich Faraj4,5, Renan Ribeiro E Ribeiro4,5, Tiago Biachi de Castria6, Bruno Zilberstein3, Venancio Avancini Ferreira Alves5, Ulysses Ribeiro3,4, Evandro Sobroza de Mello4,5. 1. Department of Gastroenterology, Instituto do Cancer, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Avenida Doutor Arnaldo, 251, São Paulo, 01246-000, Brazil. marina.pereira@hc.fm.usp.br. 2. Centro de Investigação Translacional em Oncologia (LIM24), Instituto do Cancer, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, São Paulo, Brazil. marina.pereira@hc.fm.usp.br. 3. Department of Gastroenterology, Instituto do Cancer, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Avenida Doutor Arnaldo, 251, São Paulo, 01246-000, Brazil. 4. Centro de Investigação Translacional em Oncologia (LIM24), Instituto do Cancer, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, São Paulo, Brazil. 5. Department of Pathology, Instituto do Cancer, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, São Paulo, Brazil. 6. Department of Radiology and Oncology, Instituto do Cancer, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, São Paulo, Brazil.
Abstract
BACKGROUND: The assessment of human epidermal growth factor receptor 2 (HER2), microsatellite instability (MSI) and programmed cell death-ligand 1 (PD-L1) expression is relevant for the selection and effectiveness of targeted therapy in gastric cancer (GC). OBJECTIVE: We aimed to investigate the clinicopathological characteristics and prognosis of GC patients according to these profiles. METHODS: GC patients who underwent gastrectomy with D2 lymphadenectomy were eligible. HER2, MSI status and PD-L1 expression were analyzed by immunohistochemistry (IHC). Patients were grouped as follows: HER2+ group, immunotherapy (IT) group (MSI and/or PD-L1+), and non-targeted therapy (NTT) group (stable microsatellite and HER2/PD-L1-). RESULTS: Among 282 patients, 50 (17.7%) were HER2+ and 79 (28%) MSI/PD-L1+. Fifteen had HER2+ and MSI/PD-L1+, while 168 (59.6%) were in the NTT group. HER2+ GCs were related to male gender (p = 0.007), intestinal type (p = 0.001) and less advanced pTNM stage (p = 0.029). Older age (p = 0.003), subtotal gastrectomy (p = 0.025), intestinal type (p = 0.008), pN0 status (p = 0.002) and less advanced pTNM stage (p = 0.001) were associated with the IT group. IT GC had better disease-free survival (DFS) and overall survival than the NTT group (p = 0.015 and p = 0.027, respectively). Concerning patients eligible for the standard adjuvant therapy, the treatment impacted positively on DFS for HER2+ and NTT groups (p = 0.003 and p = 0.042, respectively). No difference in DFS was seen between IT patients who received perioperative/adjuvant therapy and those treated only with surgery (p = 0.160). CONCLUSIONS: GC patients who exhibited markers that can serve as an indication for known targeted therapy represent 40.4% of cases. The IT group was associated with a better prognosis. No benefit with standard adjuvant treatment appears to be achieved in MSI/PD-L1+ GCs.
BACKGROUND: The assessment of human epidermal growth factor receptor 2 (HER2), microsatellite instability (MSI) and programmed cell death-ligand 1 (PD-L1) expression is relevant for the selection and effectiveness of targeted therapy in gastric cancer (GC). OBJECTIVE: We aimed to investigate the clinicopathological characteristics and prognosis of GCpatients according to these profiles. METHODS:GCpatients who underwent gastrectomy with D2 lymphadenectomy were eligible. HER2, MSI status and PD-L1 expression were analyzed by immunohistochemistry (IHC). Patients were grouped as follows: HER2+ group, immunotherapy (IT) group (MSI and/or PD-L1+), and non-targeted therapy (NTT) group (stable microsatellite and HER2/PD-L1-). RESULTS: Among 282 patients, 50 (17.7%) were HER2+ and 79 (28%) MSI/PD-L1+. Fifteen had HER2+ and MSI/PD-L1+, while 168 (59.6%) were in the NTT group. HER2+ GCs were related to male gender (p = 0.007), intestinal type (p = 0.001) and less advanced pTNM stage (p = 0.029). Older age (p = 0.003), subtotal gastrectomy (p = 0.025), intestinal type (p = 0.008), pN0 status (p = 0.002) and less advanced pTNM stage (p = 0.001) were associated with the IT group. IT GC had better disease-free survival (DFS) and overall survival than the NTT group (p = 0.015 and p = 0.027, respectively). Concerning patients eligible for the standard adjuvant therapy, the treatment impacted positively on DFS for HER2+ and NTT groups (p = 0.003 and p = 0.042, respectively). No difference in DFS was seen between IT patients who received perioperative/adjuvant therapy and those treated only with surgery (p = 0.160). CONCLUSIONS:GCpatients who exhibited markers that can serve as an indication for known targeted therapy represent 40.4% of cases. The IT group was associated with a better prognosis. No benefit with standard adjuvant treatment appears to be achieved in MSI/PD-L1+ GCs.
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