Immunohistochemical expression of thymidylate synthase and prognosis in gastric cancer patients submitted to fluoropyrimidine-based chemotherapy

Autor(es)

Pereira, Marina Alessandra ^[1] ; Kodama Pertille Ramos, Marcus Fernando ^[1] ; Dias, Andre Roncon ^[1] ; Faraj, Sheila Friedrich ^[2] ; Cirqueira, Cinthya dos Santos ^[3] ; de Mello, Evandro Sobroza ^[2] ; Zilberstein, Bruno ^[1] ; Ferreira Alves, Venancio Avancini ^[2] ; Ribeiro, Jr., Ulysses ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Med Sch, Canc Inst, Dept Gastroenterol, BR-01246000 Sao Paulo - Brazil

^[2] Univ Sao Paulo, Med Sch, Canc Inst, Dept Pathol, BR-01246000 Sao Paulo - Brazil

^[3] Adolfo Lutz Inst, Dept Pathol, BR-01246000 Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: CHINESE JOURNAL OF CANCER RESEARCH; v. 30, n. 5, p. 526-536, OCT 2018.
• Citações Web of Science: 2

Resumo

Objective: Adjuvant chemotherapy with 5-fluorouracil (5-FU) has been widely used in gastric cancer (GC) patients to prevent relapse after curative resection. 5-FU acts by inhibiting thymidylate synthase (TS), and high levels of TS correlate with resistance to treatment with fluoropyrimidines. The aim of this study was to evaluate the expression of TS in GC patients, and its relation with clinicopathological characteristics and prognosis in adjuvant chemotherapy with 5-FU. Methods: We retrospectively evaluated 285 patients who underwent D2-gastrectomy with curative intent. TS expression was determined by immunohistochemistry (IHC) in tumor cells by tissue microarray (TMA). TS level was evaluated according to the intensity and percentage of cells marked by a score system. Patients were divided in three groups according to their TS-score: negative, low and high. Results: TS expression was positive in 92.3% of GC. TS-high, TS-low and TS-negative were observed in 46.3%, 46.0% and 7.7% of patients, respectively. High-TS GC were associated with older age (P=0.007), high neutrophil/lymphocyte ratio (P=0.048), well/moderately differentiated histology (P=0.001), intestinal Lauren type (P<0.001) and absence of perineural invasion (P=0.003). Among 285 patients, 133 stage II/III patients (46.7%) received chemotherapy with 5-FU. In survival analysis, TS-high was associated with worse disease-free survival (DFS) in stage III GC patients who received 5-FU-based chemotherapy (P=0.007). Multivariate analysis revealed that total gastrectomy, poorly differentiated tumors and high TS-score were associated with worse DFS in stage III GC patients. Conclusions: High TS-score in stage III GC was associated with poor DFS in patients treated with fluoropyrimidine-based chemotherapy. (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