Skip to main content
PMC home page
British Journal of Cancer logoLink to British Journal of Cancer
. 1999 Oct;81(3):484–489. doi: 10.1038/sj.bjc.6690719

The expression of thymidine phosphorylase correlates with angiogenesis and the efficacy of chemotherapy using fluorouracil derivatives in advanced gastric carcinoma

H Saito 1, S Tsujitani 1, S Oka 1, A Kondo 1, M Ikeguchi 1, M Maeta 1, N Kaibara 1
PMCID: PMC2362934  PMID: 10507774

Abstract

The expression of thymidine phosphorylase (TP) and the density of microvessel in advanced gastric carcinoma were examined by immunohistochemistry to evaluate the significance of TP. The expression of TP was negative in 72 cases, positive in 54. The microvessel density correlated with the expression of TP. In total cases, patients with TP-positive tumours survived longer than those with TP-negative tumours. In patients treated with fluorouracil derivatives (FUs), the expression of TP significantly correlated with favourable prognosis and with unfavourable prognosis in those not treated with FUs. The patients with TP-positive tumours, the prognosis of patients treated with FUs was significantly better than that of those not treated with FUs. In patients with TP-positive tumours, treatment with FUs and lymph node metastasis were independent prognostic factors according to the Cox proportional hazards model. Depth of invasion and lymph node metastasis were independent prognostic factors in patients with TP-negative tumours. The determination of the expression of TP might be useful for predicting the efficacy of post-operative chemotherapy using FUs to prevent recurrence in advanced gastric carcinoma patients who undergo curative gastrectomy. © 1999 Cancer Research Campaign

Keywords: thymidine phosphorylase, microvessel, gastric cancer, chemotherapy, fluorouracil derivative

Full Text

The Full Text of this article is available as a PDF (153.2 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bosari S., Lee A. K., DeLellis R. A., Wiley B. D., Heatley G. J., Silverman M. L. Microvessel quantitation and prognosis in invasive breast carcinoma. Hum Pathol. 1992 Jul;23(7):755–761. doi: 10.1016/0046-8177(92)90344-3. [DOI] [PubMed] [Google Scholar]
  2. Folkman J. What is the evidence that tumors are angiogenesis dependent? J Natl Cancer Inst. 1990 Jan 3;82(1):4–6. doi: 10.1093/jnci/82.1.4. [DOI] [PubMed] [Google Scholar]
  3. Gasparini G., Weidner N., Bevilacqua P., Maluta S., Dalla Palma P., Caffo O., Barbareschi M., Boracchi P., Marubini E., Pozza F. Tumor microvessel density, p53 expression, tumor size, and peritumoral lymphatic vessel invasion are relevant prognostic markers in node-negative breast carcinoma. J Clin Oncol. 1994 Mar;12(3):454–466. doi: 10.1200/JCO.1994.12.3.454. [DOI] [PubMed] [Google Scholar]
  4. Hamazoe R., Maeta M., Kaibara N. Intraperitoneal thermochemotherapy for prevention of peritoneal recurrence of gastric cancer. Final results of a randomized controlled study. Cancer. 1994 Apr 15;73(8):2048–2052. doi: 10.1002/1097-0142(19940415)73:8<2048::aid-cncr2820730806>3.0.co;2-q. [DOI] [PubMed] [Google Scholar]
  5. Haraguchi M., Furukawa T., Sumizawa T., Akiyama S. Sensitivity of human KB cells expressing platelet-derived endothelial cell growth factor to pyrimidine antimetabolites. Cancer Res. 1993 Dec 1;53(23):5680–5682. [PubMed] [Google Scholar]
  6. Ishikawa F., Miyazono K., Hellman U., Drexler H., Wernstedt C., Hagiwara K., Usuki K., Takaku F., Risau W., Heldin C. H. Identification of angiogenic activity and the cloning and expression of platelet-derived endothelial cell growth factor. Nature. 1989 Apr 13;338(6216):557–562. doi: 10.1038/338557a0. [DOI] [PubMed] [Google Scholar]
  7. Ishikawa T., Sekiguchi F., Fukase Y., Sawada N., Ishitsuka H. Positive correlation between the efficacy of capecitabine and doxifluridine and the ratio of thymidine phosphorylase to dihydropyrimidine dehydrogenase activities in tumors in human cancer xenografts. Cancer Res. 1998 Feb 15;58(4):685–690. [PubMed] [Google Scholar]
  8. Kono A., Hara Y., Matsushima Y. Enzymatic formation of 5-fluorouracil from 1-(tetrahydro-2-furanyl)- 5-fluorouracil (tegafur) in human tumor tissues. Chem Pharm Bull (Tokyo) 1981 May;29(5):1486–1488. doi: 10.1248/cpb.29.1486. [DOI] [PubMed] [Google Scholar]
  9. Kono A., Hara Y., Sugata S., Karube Y., Matsushima Y., Ishitsuka H. Activation of 5'-deoxy-5-fluorouridine by thymidine phosphorylase in human tumors. Chem Pharm Bull (Tokyo) 1983 Jan;31(1):175–178. doi: 10.1248/cpb.31.175. [DOI] [PubMed] [Google Scholar]
  10. Kubota T., Sasano N., Abe O., Nakao I., Kawamura E., Saito T., Endo M., Kimura K., Demura H., Sasano H. Potential of the histoculture drug-response assay to contribute to cancer patient survival. Clin Cancer Res. 1995 Dec;1(12):1537–1543. [PubMed] [Google Scholar]
  11. Leichman C. G., Lenz H. J., Leichman L., Danenberg K., Baranda J., Groshen S., Boswell W., Metzger R., Tan M., Danenberg P. V. Quantitation of intratumoral thymidylate synthase expression predicts for disseminated colorectal cancer response and resistance to protracted-infusion fluorouracil and weekly leucovorin. J Clin Oncol. 1997 Oct;15(10):3223–3229. doi: 10.1200/JCO.1997.15.10.3223. [DOI] [PubMed] [Google Scholar]
  12. Lenz H. J., Leichman C. G., Danenberg K. D., Danenberg P. V., Groshen S., Cohen H., Laine L., Crookes P., Silberman H., Baranda J. Thymidylate synthase mRNA level in adenocarcinoma of the stomach: a predictor for primary tumor response and overall survival. J Clin Oncol. 1996 Jan;14(1):176–182. doi: 10.1200/JCO.1996.14.1.176. [DOI] [PubMed] [Google Scholar]
  13. Maeda K., Chung Y. S., Ogawa Y., Takatsuka S., Kang S. M., Ogawa M., Sawada T., Onoda N., Kato Y., Sowa M. Thymidine phosphorylase/platelet-derived endothelial cell growth factor expression associated with hepatic metastasis in gastric carcinoma. Br J Cancer. 1996 Apr;73(8):884–888. doi: 10.1038/bjc.1996.177. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Maeda K., Chung Y. S., Takatsuka S., Ogawa Y., Sawada T., Yamashita Y., Onoda N., Kato Y., Nitta A., Arimoto Y. Tumor angiogenesis as a predictor of recurrence in gastric carcinoma. J Clin Oncol. 1995 Feb;13(2):477–481. doi: 10.1200/JCO.1995.13.2.477. [DOI] [PubMed] [Google Scholar]
  15. Maehara Y., Watanabe A., Kakeji Y., Baba H., Kohnoe S., Sugimachi K. Postgastrectomy prescription of mitomycin C and UFT for patients with stage IV gastric carcinoma. Am J Surg. 1990 Sep;160(3):242–244. doi: 10.1016/s0002-9610(06)80015-2. [DOI] [PubMed] [Google Scholar]
  16. Moghaddam A., Bicknell R. Expression of platelet-derived endothelial cell growth factor in Escherichia coli and confirmation of its thymidine phosphorylase activity. Biochemistry. 1992 Dec 8;31(48):12141–12146. doi: 10.1021/bi00163a024. [DOI] [PubMed] [Google Scholar]
  17. Palmeri S., Gebbia V., Russo A., Armata M. G., Gebbia N., Rausa L. Oral tegafur in the treatment of gastrointestinal tract cancers: a phase II study. Br J Cancer. 1990 Mar;61(3):475–478. doi: 10.1038/bjc.1990.105. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Schabel F. M., Jr Concepts for treatment of micrometastases developed in murine systems. AJR Am J Roentgenol. 1976 Mar;126(3):500–511. doi: 10.2214/ajr.126.3.500. [DOI] [PubMed] [Google Scholar]
  19. Takebayashi Y., Akiyama S., 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 Aug 21;88(16):1110–1117. doi: 10.1093/jnci/88.16.1110. [DOI] [PubMed] [Google Scholar]
  20. Takebayashi Y., Yamada K., Miyadera K., Sumizawa T., Furukawa T., Kinoshita F., Aoki D., Okumura H., Yamada Y., Akiyama S. The activity and expression of thymidine phosphorylase in human solid tumours. Eur J Cancer. 1996 Jun;32A(7):1227–1232. doi: 10.1016/0959-8049(96)00061-5. [DOI] [PubMed] [Google Scholar]
  21. Toi M., Hoshina S., Takayanagi T., Tominaga T. Association of vascular endothelial growth factor expression with tumor angiogenesis and with early relapse in primary breast cancer. Jpn J Cancer Res. 1994 Oct;85(10):1045–1049. doi: 10.1111/j.1349-7006.1994.tb02904.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Weidner N., Folkman J., Pozza F., Bevilacqua P., Allred E. N., Moore D. H., Meli S., Gasparini G. Tumor angiogenesis: a new significant and independent prognostic indicator in early-stage breast carcinoma. J Natl Cancer Inst. 1992 Dec 16;84(24):1875–1887. doi: 10.1093/jnci/84.24.1875. [DOI] [PubMed] [Google Scholar]
  23. Zagzag D., Miller D. C., Sato Y., Rifkin D. B., Burstein D. E. Immunohistochemical localization of basic fibroblast growth factor in astrocytomas. Cancer Res. 1990 Nov 15;50(22):7393–7398. [PubMed] [Google Scholar]

Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK

RESOURCES