| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Clinical Trials |
Departments of General Surgery [M. Ko., S. P., L. S., H. G. B., K. H. L.], Biometry and Medical Documentation [S. S., M. Kr.], and Pathology [J. S.], University of Ulm, 89075 Ulm; Oncoscreen Research Institute, 07745 Jena [W. S., P. H., K. O., D. B.]; Department of Medicine, Städtisches Klinikum, 39002 Magdeburg [E. K.]; Department of Surgery I, Diakoniekrankenhaus, 27356 Rotenburg/Wümme [H. F. W.]; Department of General Surgery, Klinik am Eichert, 73035 Göppingen [W. B.]; and Department of Surgery, Wald-Klinikum 27548 Gera [H. S.], Germany
Purpose: Despite adjuvant 5-fluorouracil (5-FU) therapy, 
30% of patients with International Union against Cancer stage II and III colorectal cancer develop recurrence. In this study, we determined the prognostic value of thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) expression in colorectal cancer patients treated with adjuvant 5-FU.
Experimental Design: A real-time reverse transcription-PCR technique for quantitation of relative gene expression from paraffin-embedded specimen was established first. In a second step, archival paraffin-embedded primary tumor tissue of 309 patients who participated in adjuvant colorectal cancer trials was analyzed for TS and DPD mRNA expression.
Results: TS mRNA expression determined by real-time reverse transcription-PCR correlated with TS protein levels determined by TS immunoblot and immunohistochemistry in cultured colon cancer cell lines and paraffin-embedded primary tumor tissue. TS mRNA levels in fresh-frozen tissues also correlated with TS mRNA levels in corresponding paraffin sections. Among the patients receiving adjuvant 5-FU therapy, those with high TS survived longer than those with low TS, and in each TS subgroup, the ones with low DPD survived longer than the ones with high DPD levels. Multiple Cox regression analysis showed that besides tumor stage (P = 0.010), only the combination of TS and DPD expression turned out to be an independent prognostic factor for survival (P = 0.030).
Conclusions: This suggests that TS and DPD quantitation may be helpful to evaluate prognosis of patients receiving adjuvant 5-FU and that patients with high TS and low DPD may benefit from adjuvant 5-FU chemotherapy.
This article has been cited by other articles:
|
|
 |
|
  R. Soong, N. Shah, M. Salto-Tellez, B. C. Tai, R. A. Soo, H. C. Han, S. S. Ng, W. L. Tan, N. Zeps, D. Joseph, et al. Prognostic significance of thymidylate synthase, dihydropyrimidine dehydrogenase and thymidine phosphorylase protein expression in colorectal cancer patients treated with or without 5-fluorouracil-based chemotherapy Ann. Onc., May 1, 2008; 19(5): 915 - 919. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Krugluger, A. Brandstaetter, E. Kallay, J. Schueller, E. Krexner, S. Kriwanek, E. Bonner, and H. S. Cross Regulation of Genes of the Circadian Clock in Human Colon Cancer: Reduced Period-1 and Dihydropyrimidine Dehydrogenase Transcription Correlates in High-Grade Tumors Cancer Res., August 15, 2007; 67(16): 7917 - 7922. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Del Rio, F. Molina, C. Bascoul-Mollevi, V. Copois, F. Bibeau, P. Chalbos, C. Bareil, A. Kramar, N. Salvetat, C. Fraslon, et al. Gene Expression Signature in Advanced Colorectal Cancer Patients Select Drugs and Response for the Use of Leucovorin, Fluorouracil, and Irinotecan J. Clin. Oncol., March 1, 2007; 25(7): 773 - 780. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Liersch, C. Langer, B. M. Ghadimi, B. Kulle, D. E. Aust, G. B. Baretton, W. Schwabe, P. Hausler, H. Becker, and C. Jakob Lymph Node Status and TS Gene Expression Are Prognostic Markers in Stage II/III Rectal Cancer After Neoadjuvant Fluorouracil-Based Chemoradiotherapy J. Clin. Oncol., September 1, 2006; 24(25): 4062 - 4068. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Rubio-Viqueira, A. Jimeno, G. Cusatis, X. Zhang, C. Iacobuzio-Donahue, C. Karikari, C. Shi, K. Danenberg, P. V. Danenberg, H. Kuramochi, et al. An In vivo Platform for Translational Drug Development in Pancreatic Cancer Clin. Cancer Res., August 1, 2006; 12(15): 4652 - 4661. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Andre, D. Sargent, J. Tabernero, M. O'Connell, M. Buyse, A. Sobrero, J.-L. Misset, C. Boni, and A. de Gramont Current Issues in Adjuvant Treatment of Stage II Colon Cancer Ann. Surg. Oncol., June 1, 2006; 13(6): 887 - 898. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Langer, K. Specht, K. Becker, P. Ewald, M. Bekesch, M. Sarbia, R. Busch, M. Feith, H. J. Stein, J.-R. Siewert, et al. Association of Pretherapeutic Expression of Chemotherapy-Related Genes with Response to Neoadjuvant Chemotherapy in Barrett Carcinoma Clin. Cancer Res., October 15, 2005; 11(20): 7462 - 7469. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. L. Westra, H. Hollema, M. Schaapveld, I. Platteel, K. A. Oien, W. N. Keith, R. Mauritz, G. J. Peters, C. H. C. M. Buys, R. M. W. Hofstra, et al. Predictive value of thymidylate synthase and dihydropyrimidine dehydrogenase protein expression on survival in adjuvantly treated stage III colon cancer patients Ann. Onc., October 1, 2005; 16(10): 1646 - 1653. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. J. Epstein Maintenance Therapy to Suppress Micrometastasis: The New Challenge for Adjuvant Cancer Treatment Clin. Cancer Res., August 1, 2005; 11(15): 5337 - 5341. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Jakobsen, J. N. Nielsen, N. Gyldenkerne, and J. Lindeberg Thymidylate Synthase and Methylenetetrahydrofolate Reductase Gene Polymorphism in Normal Tissue As Predictors of Fluorouracil Sensitivity J. Clin. Oncol., March 1, 2005; 23(7): 1365 - 1369. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. A. Meyerhardt and R. J. Mayer Systemic Therapy for Colorectal Cancer N. Engl. J. Med., February 3, 2005; 352(5): 476 - 487. [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Cancer Research | Clinical Cancer Research |
| Cancer Epidemiology Biomarkers & Prevention | Molecular Cancer Therapeutics |
| Molecular Cancer Research | Cancer Prevention Research |
| Cancer Prevention Journals Portal | Cancer Reviews Online |
| Annual Meeting Education Book | Meeting Abstracts Online |
