Thymidine phosphorylase expression results in a decrease in apoptosis and increase in intratumoral microvessel density in human gastric carcinomas.

Thymidine phosphorylase (dThdPase)/platelet-derived endothelial cell growth factor (PD-ECGF) is expressed at higher levels in a variety of human carcinomas than in adjacent normal tissue. The higher expression is associated with an increase in intratumoral microvessel density (IMVD) and an unfavorable patient prognosis. This study examined the role of dThdPase in apoptosis, IMVD and p53 expression in human gastric carcinomas, dThdPase expression was noted in 12 (35.3%) of 34 early carcinomas, and in 20 (55.6%) of 36 advanced carcinomas. At least 10 areas consisting of carcinoma cells with diffuse dThdPase expression from the 32 dThdPase-positive tumors (category I), and 10 areas without dThdPase expression from the 38 negative tumors (category II) were selected from each case. For early gastric carcinoma, the mean IMVD was 88.8+/-19.4 in category I and 61.4+/-17.3 in category II carcinomas, while for advanced gastric carcinoma, the mean IMVD was 98.8+/-21.0 in category I and 76.0+/-27.1 in category II carcinomas. The mean IMVD was significantly higher in category I than in category II tumors (P<0.05). The mean apoptotic index (AI: percentage of apoptotic cells) was 1.95+/-1.30 in category I, and 3.76+/-1.49 in category II carcinomas for early gastric carcinoma, and 1.51+/-0.98 in category I and 2.14+/-0.66 in category II carcinomas for advanced gastric carcinoma, the value of the mean AI being significantly (P<0.05) higher in dThdPase-negative tumors (category II) than in the positive tumors (category I), regardless of tumor stage or histological type. There was a significant inverse correlation (P<0.001) between AI and IMVD. These results indicate that dThdPase expression is associated with both an increase in intratumoral microvessels and a decrease in apoptosis in human gastric carcinomas.