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We investigated whether the intensity of thymidylate synthase (TS) staining in tissue samples obtained from gastric cancer (GC) patients undergoing gastrectomy could predict response to 5-FU-based adjuvant chemotherapy after gastrectomy.Clinicopathological features of 124 patients with histologically proven GC who underwent radical gastrectomy were retrospectively reviewed. Tissue samples obtained from these patients were immunohistochemically stained for assessing TS expression. We arbitrarily classified the TS staining results as low (20% cytoplasmic immunostaining) and high (or =20% cytoplasmic immunostaining) TS expression.The clinicopathological features of the low TS expression group patients were typically similar to those of the high TS expression group patients. However, multivariate forward stepwise logistic regression analysis revealed that low TS expression was independently associated with females and responders to 5-FU-based adjuvant chemotherapy. The median follow-up duration for the 124 GC patients who had undergone curative resection was 41.3 months. The GC patients who showed poor tumor differentiation and high TS expression had short disease-free survival (DFS) and overall survival (OS).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.

Imatinib mesylate showed a sustained objective response in patients with advanced gastrointestinal stromal tumors (GISTs) since its introduction in 2001. Here we reported genetic changes during imatinib mesylate treatment especially when the patient had partial response or stationary disease. Between 2001 and June 2005, 44 advanced GIST patients were treated with imatinib mesylate. Among them, five patients (11.9%) (four with partial response and one with stationary disease) received surgical treatment during imatinib mesylate treatment. We compared the genetic status of each tumor in the five patients before and after imatinib mesylate treatment. Symptomatic gallbladder stone with or without cholecystitis (two patients), lower GI bleeding (one patient), upper GI bleeding (one patient), and enterocutaneous fistula (one patient) comprised the indications for operation. Before imatinib mesylate treatment, four of the five patients displayed deletion mutation and one patient displayed point mutation in exon 11. After treatment, one patient developed second novel missense mutation in exon 17 with acquired resistance since he was administered with only half dose of imatinib mesylate. The other four patients taking the same dose of imatinib mesylate exhibited identical mutation to the previous lesions. Necrosis of large and bulky tumors after imatinib mesylate therapy might be the reason of gastrointestinal hemorrhage and enterocutaneous fistula requiring surgical intervention. Imatinib mesylate could induce acquired resistance during treatment and second novel mutation might be the reason.