| Texto completo | |
| Autor(es): |
Pereira, Marina A.
;
Dias, Andre R.
;
Ramos, Marcus F. K. P.
;
Cardili, Leonardo
;
Moraes, Rafael D. R.
;
Zilberstein, Bruno
;
Nahas, Sergio C.
;
Mello, Evandro S.
;
Ribeiro Jr, Ulysses
Número total de Autores: 9
|
| Tipo de documento: | Artigo Científico |
| Fonte: | JOURNAL OF SURGICAL ONCOLOGY; v. 126, n. 1, p. 9-pg., 2022-07-01. |
| Resumo | |
Background Gastric cancer (GC) with microsatellite instability (MSI) is a less aggressive disease and associated with resistance to 5-fluorouracil (5-FU)-based chemotherapy (CMT). Thymidylate synthase (TS) is inhibited by 5-FU, and another potential mediator of therapeutic resistance to 5-FU. Therefore, we aimed to analyze the association between MSI and TS expression in GC, and its impact on disease outcomes. Methods We retrospectively evaluated GC who underwent D2-gastrectomy. MSI and TS were analyzed by immunohistochemistry. We also investigated p53 expression, PD-L1 status, and tumor-infiltrating lymphocytes (CD4 and CD8). Results Out of 284 GC, 60 (21.1%) were MSI. Median TS-score for all cases was 16.5. TS expression was significantly higher in MSI compared to microsatellite-stable (MSS; p < 0.001). Considering both status, GC were classified in four groups: 167 (58.8%) MSS + TS-low; 57 (20.1%) MSS + TS-High; 24 (8.5%) MSI + TS-low; and 36 (12.7%) MSI + TS-high. MSI + TS-high group had less advanced pTNM stage, higher CD8+T cells levels (p < 0.001) and PD-L1 positivity (p < 0.001). Normal p53 expression was related to MSI GC (p < 0.001). Improved survival was observed in MSI + TS-high, but no survival benefit was seen with CMT. Conclusion MSI GC was associated with high TS levels, which may explain therapeutic resistance to 5-FU. Additionally, MSI + TS-high showed better survival, but without improvement with CMT. (AU) | |
| Processo FAPESP: | 16/25524-0 - Caracterização da infecção por Helicobacter pylori, vírus Epstein-Barr e perfil da expressão gênico-proteica nos adenocarcinomas gástricos |
| Beneficiário: | Ulysses Ribeiro Júnior |
| Modalidade de apoio: | Auxílio à Pesquisa - Regular |