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

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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.

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Correspondence to Marina Alessandra Pereira.

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Funding

This research was supported by “Fundaçao de Amparo a Pesquisa do Estado de Sao Paulo” (FAPESP), grant number 2016/25524-0.

Conflict of interest

Marina Alessandra Pereira, Marcus Fernando Kodama Pertille Ramos, André Roncon Dias, Sheila Friedrich Faraj, Renan Ribeiro e Ribeiro, Bruno Zilberstein, Venancio Avancini Ferreira Alves, Ulysses Ribeiro Jr., and Evandro Sobroza de Mello declare that they have no conflicts of interest that might be relevant to the contents of this article. Tiago Biachi de Castria has received a speaker honorarium from Roche, support for travel from Roche and Ipsen, and consulting fees from AstraZeneca.

Ethical approval

The study was approved by the hospital ethics committee (NP771/2015) and registered online (http://www.plataformabrasil.com, number: 43453515.6.0000.0065).

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Pereira, M.A., Ramos, M.F.K.P., Dias, A.R. et al. Expression Profile of Markers for Targeted Therapy in Gastric Cancer Patients: HER-2, Microsatellite Instability and PD-L1. Mol Diagn Ther 23, 761–771 (2019). https://doi.org/10.1007/s40291-019-00424-y

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