Summary
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.
Similar content being viewed by others
Article PDF
Change history
16 November 2011
This paper was modified 12 months after initial publication to switch to Creative Commons licence terms, as noted at publication
References
Bosari, S, Lee, AKC, Delellis, RA, Wiley, RD, Heatley, GJ & Silverman, ML (1992). Microvessel quantitation and prognosis in invasive breast carcinoma. Hum Pathol 23: 755–761.
Folkman, J (1990). What is the evidence that tumours are angiogenesis dependent?. J Natl Cancer Inst 82: 4–6.
Gasparini, G, Weidner, N, Bevilacqua, P, Maluta, S, Palma, PD, Caffo, O, Barbareschi, M, Boracchi, P, Marubini, E & Pozza, F (1994). Tumour microvessel density, p53 expression, tumour size, and peritumoural lymphatic vessel invasion are relevant prognostic marker in node-negative breast carcinoma. J Clin Oncol 12: 454–466.
Griswold, DP Jr (1975). The potential for murine tumor models in surgical adjuvant chemotherapy. Cancer Chemother Rep 5: 187–204.
Hamazoe, R, Maeta, M & Kaibara, N (1994). Intraperitoneal thermochemotherapy for prevention of peritoneal recurrence of gastric cancer. Cancer 73: 2048–2052.
Haraguchi, M, Furukawa, T, Sumizawa, T & Akiyama, S (1993). Sensitivity of human KB cells expressing platelet-derived endothelial cell growth factor to pyrimidine antimetabolites. Cancer Res 53: 5680–5682.
Ishikawa, F, Miyazono, K, Hellman, U, Drexler, H, Wernstedt, C, Hagiwara, K, Usuki, K, Takaku, F, Risau, W & Heldin, CH (1989). Identification of angiogenic activity and the cloning and expression of platelet-derived endothelial cell growth factor. Nature 338: 557–562.
Ishikawa, T, Sekiguchi, F, Fukase, Y, Sawada, N & Ishitsuka, H (1998). 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 58: 685–690.
Japanese Research Society for Gastric Cancer (1995). Japanese Classification of Gastric Carcinoma. Kanehara: Tokyo.
Kono, A, Hara, Y & Matsushima, Y (1981). Enzymatic formation of 5-fluorouracil from 1-(tetrahydro-2-furanyl)-5-fluorouracil (tegafur) in human tumor tissues. Chem Pharm Bull 29: 1486–1488.
Kono, H, Hara, Y, Sugata, S, Karube, Y, Matsushima, Y & Ishitsuka, H (1983). Activation of 5′-deoxy-5-fluorouridine by thymidine phosphorylase in human tumor tissues. Chem Pharm Bull, (Tokyo)31: 175–178.
Kubota, T, Sasano, N, Abe, O, Nakao, I, Kawamura, E, Saito, T, Endo, M, Kimura, K, Demura, H, Sasano, H, Nagura, H, Ogawa, N & Hoffman, RM . The Chemosensitivity Study Group for the Histoculture Drug-response Assay (1995). The potential of the histoculture drug response assay to contribute to cancer patient survival. Clin Cancer Res 1: 1537–1543.
Leichman, CG, Lenz, HJ, Leichman, L, Danenberg, K, Baranda, J, Groshen, S, Boswell, W, Metzger, R, Tan, M & Danenberg, PV (1997). Quantitation of intratumoral thymidylate synthase expression predicts for disseminated colorectal cancer response and resistance to protracted-infusion fluorouracil and weekly leucovorin. J Clin Oncol 15: 3223–3229.
Lenz, HJ, Leichman, CG, Danenberg, KD, Danenberg, PV, Groshen, S, Cohen, H, Laine, L, Crookes, P, Silberman, H, Baranda, J, Garcia, Y, Li, J & Leichman, L (1995). Thymidylate synthase mRNA level in adenocarcinoma of the stomach: a predictor for primary tumor response and overall survival. J Clin Oncol 14: 176–182.
Maeda, K, Chung, YS, Takatsuka, S, Ogawa, Y, Sawada, T, Yamashita, Y, Onoda, N, Kato, Y, Nitta, A, Arimoto, Y, Kondo, Y & Sowa, M (1995). Tumor angiogenesis as a predictor of recurrence in gastric carcinoma. J Clin Oncol 13: 477–481.
Maeda, K, Chung, YS, Ogawa, Y, Takatuska, S, Kang, SM, Ogawa, M, Sawada, T, Onoda, N, Kato, Y & Sowa, M (1996). Thymidine phosphorylase/platelet-derived endothelial cell growth factor expression associated with hepatic metastasis in gastric carcinoma. Br J Cancer 73: 884–888.
Maehara, Y, Watanabe, A, Kakeji, Y, Baba, H, Kohnoe, S & Sugimachi, K (1990). Postoperative prescription of mitomycin C and UFT for patients with stage IV gastric carcinoma. Am J Surg 160: 242–244.
Moghaddam, A & Bicknell, R (1992). Expression of platelet-derived endothelial cell growth factor in Escherichia coli and confirmation of its thymidine phosphorylase activity. Biochemistry 31: 12141–12146.
Nishida, M, Hino, A, Mori, K, Matsumoto, T, Tanaka, Y & Ishitsuka, H (1994). Cloning of hybridomas producing anti-human thymidine phosphorylase (dThdPase) and establishment ELISA for measuring dThdPase. J Jpn Soc Cancer Ther 29: 1192.
Palmeri, S, Gebbia, V, Russo, A, Armata, MG, Gebbia, N & Rausa, L (1990). Oral tegafur in the treatment of gastrointestinal tract cancers: a phase II study. Br J Cancer 61: 475–478.
Schabel, FM Jr (1976). Concepts for treatment of micrometastases developed in murine systems. AJR Am J Roentgenol 126: 500–511.
Schabel, FM Jr (1977). Surgical adjuvant chemotherapy of metastatic murine tumors. Cancer 40: 58–68.
Takebayashi, Y, Akiyama, Y, Akiba, S, Yamada, K, Miyadera, K, Sumizawa, T, Yamada, Y, Murata, F & Aikou, T (1996). Clinicopathologic and prognostic significance of an angiogenic factor, thymidine phosphorylase, in human colorectal carcinoma. J Natl Cancer Inst 88: 1110–1117.
Takebayashi, Y, Yamada, K, Miyadera, K, Sumizawa, T, Furukawa, T, Kinoshita, F, Aoki, D, Okumura, H, Yamada, Y, Akiyama, S & Aikou, T (1996). The activity and expression of thymidine phosphorylase in human solid tumors. Eur J Cancer 32: 1227–1232.
Toi, M, Hoshina, S, Takayanagi, T & Tominaga, T (1994). Association of vascular endothelial growth factor expression with tumor angiogenesis and with early relapse in primary breast carcinoma. Jpn J Cancer Res 85: 1045–1049.
Weidner, N, Folkman, J, Pozza, F, Bevilacqua, P, Allred, EN, Moore, DH, Meli, S & Gasparini, G (1992). Tumour angiogenesis: a new significant and independent prognostic indicator in early-stage breast carcinoma. J Natl Cancer Inst 84: 1875–1887.
Zagzag, D, Miller, DC, Sato, Y, Rifkin, DB & Burstein, DE (1990). Immunohistochemical localization of basic fibroblast growth factor in astrocytomas. Cancer Res 50: 7393–7398.
Author information
Authors and Affiliations
Additional information
Correspondence to: H Saito
Rights and permissions
From twelve months after its original publication, this work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/
About this article
Cite this article
Saito, H., Tsujitani, S., Oka, S. et al. The expression of thymidine phosphorylase correlates with angiogenesis and the efficacy of chemotherapy using fluorouracil derivatives in advanced gastric carcinoma. Br J Cancer 81, 484–489 (1999). https://doi.org/10.1038/sj.bjc.6690719
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.bjc.6690719
Keywords
This article is cited by
-
Early tumor response to induction chemotherapy or chemoradiotherapy is a significant prognostic predictor in patients with initially unresectable T4 esophageal cancer following subsequent surgery
Esophagus (2015)
-
Comparison of thymidine phosphorylase expression and prognostic factors in gallbladder and bile duct cancer
BMC Cancer (2010)
-
Suppression of thymidine phosphorylase expression by promoter methylation in human cancer cells lacking enzyme activity
Cancer Chemotherapy and Pharmacology (2008)
-
Molecular Markers for Gastric Adenocarcinoma
Molecular Diagnosis & Therapy (2006)
-
Genetic factors influencing Pyrimidine-antagonist chemotherapy
The Pharmacogenomics Journal (2005)