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

查看全文 作　　者：Marina Alessandra [1]Pereira;Marcus Fernando Kodama Pertille [1]Ramos;ANDre Roncon [1]Dias;Sheila Friedrich [2]Faraj;Cinthya dos Santos [3]Cirqueira;EvANDro Sobroza de [2]Mello;Bruno [1]Zilberstein;Venancio Avancini Ferreira [2]Alves;Ulysses Ribeiro [1]Jr 高影响力作者 机构地区：[1]Department of Gastroenterology,Cancer Institute,University of Sao Paulo Medical School;[2]Department of Pathology,Cancer Institute,University of Sao Paulo Medical School;[3]Department of Pathology,Instituto Adolfo Lutz高影响力机构 出　　处：《Chinese Journal of Cancer Research》索引2018年第30卷第5期,共11页高影响力期刊 基　　金：supported by Fundacao de Amparo a Pesquisa do Estado de Sao Paulo(FAPESP agency)(No2016/25524-0) 摘　　要：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 in46.3%, 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. 关 键 词：Gastric cancer adjuvant therapy thymidylate synthase 5-fluorouracil-based chemotherapy
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