Abundant expression of thymidine phosphorylase (TP) mRNA and protein was observed in human carcinoma tissues relative to the corresponding normal tissues. However, the distribution of cells that express TP has not yet been determined. In this study, we examined enzyme activity of TP in 24 primary colorectal carcinoma tissues and the corresponding normal tissue. Using in situ reverse-transcription polymerase chain reaction (RT-PCR), a new methodology to determine the localization of genes of interest objectively and clearly, cell distribution was compared. The expression of TP mRNA is observed in normal infiltrating cells adjacent to colon carcinoma cells by in situ RT-PCR. Similar to the protein activity, the average TP mRNA expression (amplified products/×400 field) in cases of Dukes C and D is 76.8, while that of Dukes A and B is 42.5, being significantly different (p = 0.001). Moreover, the number of amplified products in colon carcinoma tissues showed a significant correlation with the enzyme activity evaluated by high-performance liquid chromatography (p < 0.01, R = 0.76). In conclusion, the expression of TP mRNA is localized in stromal tissues as determined by in situ RT-PCR and can reflect the level of TP enzyme activity.

1.
Mimori K, Mori M, Ueo H, Baba K, Haraguchi M, Akiyoshi T: Clinical significance of pyrimidine nucleoside phosphorylase in colorectal carcinoma. Int J Oncol 1996;10:493–496.
2.
Furukawa T, Yoshimura A, Sumizawa T, Haraguchi M, Akiyama S: Angiogenic factor. Nature 1992;356:668–668.
3.
Miyazono K, Okabe T, Urabe A, Takaku F, Heldin C: Purification and properties of an endothelial cell growth factor from human platelets. J Biol Chem 1987;262:4098–4103.
4.
Matsuura T, Kuratate I, Teramachi K, Osaki M, Fukuda Y, Ito H: Thymidine phosphorylase expression is associated with both increase of intratumoral microvessels and decrease of apoptosis in human colorectal carcinomas. Cancer Res 1999;59:5037–5040.
5.
Larrivee B, Karsan A: Signaling pathway induced by vascular endothelial growth factor. Int J Mol Med 2000;5:447–456.
6.
Lee J, Chow N, Wang S, Huang S: Prognostic value of vascular endothelial growth factor expression in colorectal cancer patients. Eur J Cancer 2000;36:748–753.
7.
Fox SB, Moghaddam A, Westwood M, Turley H, Bicknell R, Gatter KC, Harris AL: Platelet-derived endothelial cell growth factor/thymidine phosphorylase expression in normal tissues: An immunohistochemical study. J Pathol 1995;176:183–190.
8.
Takahashi Y, Bucana CD, Liu W, Yoneda J, Kitadai Y, Karen R, Cleary KR, Ellis LM: Platelet-derived endothelial cell growth factor in human colon cancer angiogenesis: Role of infiltrating cells. J Natl Cancer Inst 1996;88:1146–1151.
9.
Takebayashi Y, Akiyama S-I, Akiba S, Yamada K, Miyadera K, Sumizawa T, Yamada Y, Murata F, Aikou T: Clinicopathologic and prognostic significance of an angiogenic factor, thymidine phosphorylase, in human colorectal carcinoma. J Natl Cancer Inst 1996;88:1110–1117.
10.
Eda H, Fujimoto K, Watanabe S, Ura M, Hino A, Tanaka Y, Wada K, Ishitsuka H: Cytokines induce thymidine phosphorylase expression in tumor cells and make them more susceptible to 5′-deoxy-5-fluorouridine. Cancer Chemother Pharmacol 1993;32:333–338.
11.
Sgroi DC, Teng S, Robinson G, LeVangie R, Hudson JR Jr, Elkahloun AG: In vivo gene expression profile analysis of human breast carcinoma progression. Cancer Res 1999;59:5656–5661.
12.
Emmert-Buck M, Bonner R, Smith P, Chuaqui R, Zhuang Z, Goldstein S, Weissw R, Liotta L: Laser capture microdissection. Science 1996;274:998–1001.
13.
Eberwine J, Yeh H, Miyashiro K, Clao Y, Nair S, Zettel RF, Coleman P: Analysis of gene expression in single live neurons. Proc Natl Acad Sci USA 1992;89:3010–3014.
14.
Luo L, Salunga R, Guo H, Bittner A, Joy K, Galindo J, Xiao H, Rogers K, Wan J, Jackson M, Erlander M: Gene expression profiles of laser-captured adjacent neuronal subtypes. Nat Med 1999;5:117–122.
15.
van Triest B, Pinedo HM, Blaauwgeers JL, van Diest PJ, Schoenmakers PS, Voorn DA, Smid K, Hoekman K, Hoitsma HF, Peters GJ: Prognostic role of thymidylate synthase, thymidine phosphorylase/platelet-derived endothelial cell growth factor, and proliferation markers in colorectal cancer. Clin Cancer Res 2000;6:1063–1072.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.