Thymidine phosphorylase expression causes both the increase of intratumoral microvessels and decrease of apoptosis in human esophageal carcinomas

Abstract

Thymidine phosphorylase (dThdPase)/platelet-derived endothelial cell growth factor, is expressed at higher levels in tumor tissues compared to the adjacent normal tissues in a variety of human carcinomas. The higher expression is associated with an increase of intratumoral microvessel density (IMVD) and an unfavorable patient prognosis. We examined the role of dThdPase in apoptosis, IMVD, P53 expression and patient prognosis of human stages II and III esophageal squamous cell carcinomas (SCC). dThdPase expression was noted in 52 of the 78 esophageal SCC (66.7%), regardless of tumor stages and histologic grades. Mean IMVD was 117.9 +/- 32.6 in the dThdPase-positive cases and 103.1 +/- 21.5 in the dThdPase-negative cases, the value being significantly higher in the former (P < 0.05). Similarly, median (range) apoptotic index (AI: percentage of apoptotic cells) was significantly lower in the dThdPase-positive SCC, 1.8 (0.4-6.5), than in the dThdPase-negative SCC, 3.7 (0.6-7.0) (P < 0.01). AI and IMVD showed a significant inverse correlation (r = - 0.31, P = 0.005). There was also no significant difference in the frequency of P53 expression between the dThdPase-positive SCC and the negative SCC. No statistical difference was noted regarding the postoperative survival rate between the dThdPase-positive and the negative SCC. Although dThdPase expression was not associated with patient prognosis, the expression provided an advantage for tumor growth of human esophageal SCC, not only by increasing the intratumoral microvessels, but also attenuation of apoptosis, which might occur via a p53 gene-independent pathway.