Ibrahim Gama1, Maria Vieria1, Diana Martins1,2,3,4,5, Paulo Teixeira6, Maria de Fátima Silva 6, Fernando Melo7, Inês Bolais7, Inês Colaço7, Sara Andrade7, Rui Caetano Oliveira 8, Inês Ferreira 8, Patrícia Carreira8, Clara Rocha 9,10, Fernando Mendes *1,2,3,4,5,6,11

1 – Politécnico de Coimbra, ESTeSC, UCPCBL, Rua 5 de Outubro–SM Bispo, Apartado 7006, 3046-854 Coimbra, Portugal

2 – Laboratório de Investigação em Ciências Aplicadas à Saúde (LabinSaúde), Politécnico de Coimbra, ESTESC, Rua 5 de Outubro–SM Bispo, Apartado 7006, 3046-854 Coimbra, Portugal

3 – Coimbra Institute for Clinical and Biomedical Research (iCBR) Area of Environment Genetics and Oncobiology (CIMAGO), Biophysics Institute of Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal

4 – Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3004-504 Coimbra, Portugal

5 – Clinical Academic Center of Coimbra (CACC), 3004-561 Coimbra, Portugal

6- Pathology Service, Coimbra Hospital and University Centre, Coimbra, Portugal

7 – Surgery Service, Hospital Distrital da Figueira da Foz, E.P.E., Figueira da Foz, Portugal

8 – Germano de Sousa – Centro de Diagnóstico Histopatológico CEDAP, Coimbra, Portugal

9 – Politécnico de Coimbra, ESTeSC, UCPNS, Rua 5 de Outubro–SM Bispo, Apartado 7006, 3046-854 Coimbra, Portugal

10 – Institute for Systems Engineering and Computers at Coimbra, Coimbra, Portugal

11 – European Association for Professions in Biomedical Sciences, B-1000 Brussels, Belgium

* Corresponding author:Fernando Mendes, email: fjmendes@estesc.ipc.pt

DOI: https://doi.org/10.17532/dzn.2023.006

Introduction: Gastric cancer (GC) is the fifth most common cancer and one of the most common causes of cancer death worldwide.  Systemic chemotherapy, radiotherapy and surgery are the current treatment options. However, the poor outcomes indicate the need for more effective treatment strategies in order to improve patients survival rates.  DNA mismatch repair (MMR) deficiency has received increasing attention as a biomarker of anti-PD-L1 treatments of solid tumors including gastric cancer (GC).

Aim: Our aim was to explore the expression of DNA MMR, PD-L1, and Ki-67 expression in GC patients and evaluate its clinicopathological and prognostic significance.

Material & Methods: We performed a retrospective study assessing DNA MMR status, Ki-67, and PD-L1 expression in 30 GC patients using immunohistochemistry staining for MLH1, MSH2, MSH6, PMS2, Ki-67 and PD-L1. Clinicopathological features, disease-free survival, and overall survival (OS) were collected from all patients.

Results: Expression of MMR proteins was observed in 40% of GC samples. The remaining samples exhibited an altered pattern of MMR protein. High PD-L1 expression was observed in 33,3% of the cases and Ki-67 expression in 53%. The results demonstrate that patients with MSI tumours demonstrated a better OS than MSS patients. The results also demonstrate a positive correlation between PD-L1 expression, advanced age and Ki-67 expression.

Conclusion: These results prove preliminary evidence that patients with the MSI GC show better outcome than MSS GC and that patients with MSI tumours can have potential better outcomes with immunotherapy. Although multicenter studies with additional molecular investigation are required to explore these tumors, the results demonstrate that MMR and MSI associated with PD-L1 could be important in GC treatment and outcome.

Keywords: Gastric cancer, DNA mismatch repair, PD-L1, Ki-67