Expression of thymidylate synthase determines the response of gastric cancer patients undergoing gastrectomy to 5-fluorouracil-based adjuvant chemotherapy

Abstract

Low TS expression is significantly associated with female GC patients and responders to 5-FU-based adjuvant chemotherapy. It predicts longer DFS and OS in selected GC patients treated with 5-FU-based adjuvant chemotherapy after curative resection. The results suggest that prospective assessment of TS staining intensity in tissue samples obtained from GC patients undergoing gastrectomy would be useful to predict the patients who would be benefited from 5-FU-based adjuvant chemotherapy after gastrectomy.

Human equilibrative nucleoside transporter 1 expression is a strong independent prognostic factor in UICC T3—T4 pancreatic cancer patients treated with preoperative gemcitabine‐based chemoradiotherapy

“…A large number of studies on gastrointestinal and other cancers treated with 5‐FU‐based chemotherapy have demonstrated that high TS and high DPD intratumoral expressions are associated with 5‐FU resistance. High TS expression has been reported to be associated with poor prognosis in colon and gastric cancer patients treated with 5‐FU‐based chemotherapy [35, 36], although the role of TS expression in pancreatic cancer is controversial [19, 37]. Interestingly, Komori et al [21] recently revealed that high TS expression was correlated with gemcitabine resistance and poor RFS in pancreatic cancer patients with resection who were treated with adjuvant gemcitabine therapy.…”

A Pilot Study to Investigate the Role of Thymidylate Synthase as a Marker of Prognosis for Neoadjuvant Chemotherapy in Gastric and Gastro-Oesophageal Junction Adenocarcinoma

“…It is difficult to compare the level of expression seen with other values reported in the literature because of the variety of approaches used to determine positivity. TS expression was reported in 56% (64/114, semiquantitative) of oesophageal adenocarcinoma [13]; 66% (82/124, ≥20% cytoplasmic immunostaining taken as positive) of stomach cancers [16]; and 61% (19/31, same method as used here) of oesophageal adenocarcinoma [20]. In colorectal cancers, positive TS expression was seen in 72% (Grades 2, 3 versus 0, 1) [22] and 70% (semiquantitative, 0–2/3-4) [23] of patients.…”

“…In gastric cancer TS expression has been studied as a predictive marker of response to chemotherapy [14–16] and poor differentiation [17]. Patients in the United Kingdom with operable gastric and gastro-oesophageal junction (GOJ) tumours receive neoadjuvant chemotherapy prior to surgical resection according to the United Kingdom Medical Research Council Adjuvant Gastric Infusional Chemotherapy protocol [7].…”

Predictive V16alue of Thymidylate Synthase Expression in Gastric Cancer: A Systematic Review with Meta-analysis

“…In three studies (Boku et al, 1998;Yeh et al, 1998;Miyamoto et al, 2000), staining intensity grades lower than 1 or 2 represented low levels of TS expression. In five studies (Choi et al, 2001;Tahara et al, 2004;Boku et al, 2007;Lee et al, 2008;Yeh et al, 2010), expression was dichotomized by quantifying the proportion of stained cells using arbitrary thresholds of 20% or 25%. In two studies (Kwon HC et al, 2007;Kim KH et al, 2011), cases were defined as high expression on the condition that the grades of intensity and extent are both 2 or higher.…”

“…In the study by Boku et al (Boku et al, 2007), ORR data were presented separately for patients who received 5-fluorouracil (5-FU) or 5-FU/ Cisplatin, therefore two patient cohorts were considered separately for pooling. In the adjuvant disease setting, nine studies that included survival data of total 1,235 patients available for pooling (median: 103, range: 39-463) were eligible (Suda et al, 1999;Choi et al, 2001;Cho et al, 2006;Hua et al, 2007;Lee et al, 2008;Ishido et al, 2009;Kim et al, 2009;Yeh et al, 2010;Kim et al, 2011). Adjuvant fluoropyrimidine chemotherapy was given postoperatively to all patients.…”