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Thymidine Phosphorylase Expression Is Associated with Both Increase of Intratumoral Microvessels and Decrease of Apoptosis in Human Colorectal Carcinomas¹

First Department of Pathology, Tottori University, Faculty of Medicine, Yonago 683-8503 [T. M., I. K., K. T., M. O., H. I.]; and Department of Surgery, Hiroshima Prefectural Hospital, Hiroshima 734-0004 [Y. F.], Japan

Thymidine phosphorylase (dThdPase)/platelet-derived endothelial cell growth factor is expressed at higher levels in a variety of human carcinomas than it is in adjacent normal tissue. 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, cell proliferation, IMVD, and p53 expression in human colorectal carcinomas. dThdPase expression was noted in 13 of 36 (36.1%) Dukes’ A and B carcinomas and in 13 of 28 (46.3%) Dukes’ C and D carcinomas. At least 10 areas consisting of carcinoma cells with diffuse dThdPase expression from the 26 dThdPase-positive tumors (category I) and 10 areas without dThdPase expression from the 38 negative tumors (category II) were selected from each case. For stage A and B tumors, the mean IMVDs were 64.8 ± 33.7 in category I and 33.2 ± 12.6 in category II tumors, whereas for stage C and D tumors, the mean IMVDs were 77.6 ± 27.2 in the category I and 34.7 ± 14.0 in the category II tumors. The mean IMVD was significantly higher in category I than in category II tumors (P < 0.01). The mean apoptotic indices (AIs; percentage of apoptotic cells) were 2.7 ± 1.7 in the category I and 5.4 ± 2.2 in the category II carcinomas of stages A and B and 1.4 ± 0.5 in category I and 5.3 ± 2.3 in category II carcinomas of stages C and D, and the value of the mean AI was significantly lower in category I than in category II (P < 0.01), regardless of the Dukes’ stage. AI and IMVD showed a significant inverse correlation (P < 0.001). There was no significant difference in the frequency of p53 expression between the two categories. These results indicated that dThdPase expression provides an advantage for tumor growth of human colonic carcinomas not only by increasing the intratumoral microvessels but also by attenuation of apoptosis, which might occur via a p53 gene-independent pathway.

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