Expression Profile of Markers for Targeted Therapy in Gastric Cancer Patients: HER-2, Microsatellite Instability and PD-L1

• Published in: Molecular diagnosis & therapy 2019-12, Vol.23 (6), p.761-771
• Main Authors: Pereira, Marina Alessandra, Ramos, Marcus Fernando Kodama Pertille, Dias, André Roncon, Faraj, Sheila Friedrich, Ribeiro, Renan Ribeiro e, de Castria, Tiago Biachi, Zilberstein, Bruno, Alves, Venancio Avancini Ferreira, Ribeiro, Ulysses, de Mello, Evandro Sobroza
• Format: Article
• Language: English
• Subjects: Apoptosis; Biomedical and Life Sciences; Biomedicine; Cancer; Cancer Research; Cancer therapies; Cell death; Chemotherapy; Cloning; Epidermal growth factor; ErbB-2 protein; FDA approval; Gastrectomy; Gastric cancer; Gastrointestinal surgery; Growth factors; Human Genetics; Immunohistochemistry; Immunotherapy; Intestine; Laboratory Medicine; Ligands; Markers; Medical prognosis; Metastasis; Microsatellite instability; Molecular Medicine; Monoclonal antibodies; Original Research Article; Patients; PD-L1 protein; Pharmacotherapy; Prognosis; Stability analysis; Statistical analysis; Surgery; Survival; Therapy; Tumors
• ISSN: 1177-1062; 1179-2000
• DOI: 10.1007/s40291-019-00424-y

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.