Preoperative treatment with tegafur suppositories enhances apoptosis and reduces the intratumoral microvessel density of human colorectal carcinoma

BACKGROUND. This study examined the effect of tegafur, a depot of 5-fluorou racil, in human colorectal carcinomas in terms of apoptosis, cell prolifera tion, and expression of p53 gene and angiogenesis-related molecules. METHODS. A total of 32 patients with colorectal carcinoma were divided into 2 groups; 20 patients received tegafur suppositories (TS) at 1 g/day for 1 4 days before surgery, and 12 patients did not receive any chemotherapy. Su rgically removed specimens were examined immunohistochemically for Ki-67, C D34, p53, p21, Bar, vascular endothelial growth factor (VEGF), and thymidin e phosphorylase (dThd-Pase). Apoptotic tumor cells were visualized by the t erminal deoxynucleotidyl transferase (TdT)-mediated dUTP-digoxigenin nick-e nd labeling (TUNEL) procedure. RESULTS. The mean percentage of apoptotic index (AI)was 6.9 +/- 1.2 in the 20 TS-treated tumors and 4.4 +/- 1.0 in the 12 nontreated tumors (P < 0.001 ). In contrast, the mean percentage of Ki-67 labeling index (KI) became sig nificantly lower in the former group (P < 0.05). The frequency of p21 expre ssion was significantly higher in the TS-treated group than in the nontreat ed group (P < 0.05), whereas no difference was detected in p53 and Bar expr ession between the two groups. The mean intratumoral microvessel density wa s 47.8 +/- 19.8 in the TS-treated tumors and 66.8 +/- 16.5 in the nontreate d tumors (P < 0.01). The frequency of dThdPase expression, but not of VEGF expression, became significantly lower with the TS treatment. p53 expressio n did not correlate with Al, KI, IMV density, or the expression of VEGF, p2 1, or Bar, except for dThdPase, which was significantly higher in the 18 p5 3 positive tumors (P < 0.05). CONCLUSIONS. Preoperative TS treatment enhances apoptosis and suppresses an giogenesis of colorectal carcinomas in a p53-independent manner. (C) 2000 A merican Cancer Society.