Role of thrombospondin 1 (THBS1) expression in peritoneal metastasis of gastric cancer treated with taxanes.
57 Background: To clarify the utility of taxanes and to pick up the prognostic factors in the treatment with 5FU- based chemotherapy for peritoneal metastasis of gastric cancer. Methods: Responder analysis: 18 patients with peritoneal metastasis of gastric cancer were enrolled in phase I study. The regimen consists of S-1 (80-120 mg) for 14 days and intraperitoneal infusion of PTX (dose escalation: 40 - 100 mg/m2) at day 1 and 14, which was repeated 2 cycles. To pick up the predictive factors, the 137 genes, which were selected in the viewpoint of sensitivity of 5FU, CPT11 and taxanes, were analyzed using focused DNA microarray for the 12 patients. Role of THBS1 expression: THBS1 expressions were evaluated in immunohistochemical (IHC) staining of surgical specimens of 59 patients with peritoneal metastasis of gastric cancer who were administered 5FU-based chemotherapy. THBS1 positive was defined > 30% of the population stained moderate to strong. Results: Responder analysis: Expressions of THBS1 gene of the 6 patients who had clinical benefits (2: partial response, 2: positive adenocarcinoma cells in peritoneal cytology became negative, 2: remarkable decrease of ascites) were more than 2 folds higher than those of no responders. THBS1 expression was confirmed in 5 (83.3%) using IHC staining, who had significantly higher survival rate compared with that of the negative. Role of THBS1 expression: 17 patients (28.8%) was THBS1 positive and had significantly better prognosis compared with negative patients (1year survival: 64.7% vs 34.7%). 38 patients treated with regimes including taxanes revealed a tendency of improved overall survival rates (p=0.05). Overall survival of 15 patients with THBS1 positive administered taxanes was significantly higher than that of the negative patients. (1 year survival: 66.7% vs 42.4%) Conclusions: PTX could improve the survival of peritoneal metastasis of gastric cancer. THBS1 is a prognostic factor especially in the patients treated with taxanes, which leads to tailor-made therapy. [Table: see text]