Advertisement
Journal of Clinical Oncology  
Search for:
Limit by:
  Browse by Subject or Issue
Home Search or Browse JCO Subscriptions PDA Services My JCO Customer Service

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Purchase Article
Right arrow View Shopping Cart
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a colleague
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Save to my personal folders
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Shirota, Y.
Right arrow Articles by Lenz, H.-J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Shirota, Y.
Right arrow Articles by Lenz, H.-J.
Journal of Clinical Oncology, Vol 19, Issue 23 (December), 2001: 4298-4304
© 2001 American Society for Clinical Oncology

SPECIAL ARTICLE

ERCC1 and Thymidylate Synthase mRNA Levels Predict Survival for Colorectal Cancer Patients Receiving Combination Oxaliplatin and Fluorouracil Chemotherapy

By Yoshinori Shirota, Jan Stoehlmacher, Jan Brabender, Yi-Ping Xiong, Hiroyuki Uetake, Kathleen D. Danenberg, Susan Groshen, Denise D. Tsao-Wei, Peter V. Danenberg, Heinz-Josef Lenz

From the University of Southern California/Norris Comprehensive Cancer Center and Response Genetics Inc, Los Angeles, CA.

Address reprint requests to Heinz-Josef Lenz, MD, Gastrointestinal-Oncology Program, University of Southern California/Norris Comprehensive Cancer Center, Ste 3456, 1441 Eastlake Ave, Los Angeles, CA 90033; email: lenz{at}hsc.usc.edu

PURPOSE: To test the hypotheses of whether the relative mRNA expression of the thymidylate synthase (TS) gene and the excision cross-complementing (ERCC1) gene are associated with response to and survival of fluorouracil (5-FU)/oxaliplatin chemotherapy in metastatic colorectal cancer.

PATIENTS AND METHODS: Patients had progressive stage IV disease after unsuccessful 5-FU and irinotecan chemotherapy. All patients were evaluated for eligibility for a compassionate 5-FU/oxaliplatin protocol. cDNA was derived from paraffin-embedded tumor specimens to determine TS and ERCC1 mRNA expression relative to the internal reference gene beta-actin using fluorescence-based, real-time reverse transcriptase polymerase chain reaction.

RESULTS: The median TS gene expression level from 50 metastasized tumors was 3.4 x 10-3 (minimum expression, 0.18 x 10-3;maximum expression, 11.5 x 10-3), and the median ERCC1 gene expression level was 2.53 x 10-3 (minimum, 0.0; maximum, 14.61 x 10-3). The gene expression cutoff values for chemotherapy nonresponse were 7.5 x 10-3 for TS and 4.9 x 10-3 for ERCC1. The median survival time for patients with TS <= 7.5 x 10-3 (43 of 50 patients) was 10.2 months, compared with 1.5 months for patients with TS greater than 7.5 x 10-3 (P < .001). Patients with ERCC1 expression <= 4.9 x 10-3 (40 of 50 patients) had a median survival time of 10.2 months, compared with 1.9 months for patients with ERCC1 expression greater than 4.9 x 10-3 (P < .001). A TS of 7.5 x 10-3 segregated significantly into response, stable disease, and progression (P = .02), whereas the association between ERCC1 and response did not reach statistical significance (P = .29).

CONCLUSION: These data suggest that intratumoral ERCC1 mRNA and TS mRNA expression levels are independent predictive markers of survival for 5-FU and oxaliplatin combination chemotherapy in 5-FU–resistant metastatic colorectal cancer. Precise definition of the best TS cut point will require further analysis in a large, prospective study.




This article has been cited by other articles:


Home page
 Eur. J. Cardiothorac. Surg.Home page
D. Breen and F. Barlesi
The place of excision repair cross complementation 1 (ERCC1) in surgically treated non-small cell lung cancer
Eur. J. Cardiothorac. Surg., May 1, 2008; 33(5): 805 - 811.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
L. P. Martin, T. C. Hamilton, and R. J. Schilder
Platinum Resistance: The Role of DNA Repair Pathways
Clin. Cancer Res., March 1, 2008; 14(5): 1291 - 1295.
[Abstract] [Full Text] [PDF]

Home page
 Am Soc Clin Oncol Ed BookHome page
G. Bepler
Genes Predictive of Chemotherapeutic Efficacy in Non-small Cell Lung Cancer
ASCO Educational Book, January 1, 2008; 2008(1): 350 - 352.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
S. Kopetz, A. N. Shah, and G. E. Gallick
Src Continues Aging: Current and Future Clinical Directions
Clin. Cancer Res., December 15, 2007; 13(24): 7232 - 7236.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
M. Cobo, D. Isla, B. Massuti, A. Montes, J. M. Sanchez, M. Provencio, N. Vinolas, L. Paz-Ares, G. Lopez-Vivanco, M. A. Munoz, et al.
Customizing Cisplatin Based on Quantitative Excision Repair Cross-Complementing 1 mRNA Expression: A Phase III Trial in Non-Small-Cell Lung Cancer
J. Clin. Oncol., July 1, 2007; 25(19): 2747 - 2754.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
A. Handra-Luca, J. Hernandez, G. Mountzios, E. Taranchon, J. Lacau-St-Guily, J.-C. Soria, and P. Fouret
Excision Repair Cross Complementation Group 1 Immunohistochemical Expression Predicts Objective Response and Cancer-Specific Survival in Patients Treated by Cisplatin-Based Induction Chemotherapy for Locally Advanced Head and Neck Squamous Cell Carcinoma
Clin. Cancer Res., July 1, 2007; 13(13): 3855 - 3859.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
W.-S. Wang, P.-M. Chen, T.-J. Chiou, J.-H. Liu, J.-K. Lin, T.-C. Lin, H.-S. Wang, and Y. Su
Epidermal Growth Factor Receptor R497K Polymorphism Is a Favorable Prognostic Factor for Patients with Colorectal Carcinoma
Clin. Cancer Res., June 15, 2007; 13(12): 3597 - 3604.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
P. J. O'Dwyer, S. G. Eckhardt, D. G. Haller, J. Tepper, D. Ahnen, S. Hamilton, A. B. Benson III, M. Rothenberg, N. Petrelli, H.-J. Lenz, et al.
Priorities in Colorectal Cancer Research: Recommendations From the Gastrointestinal Scientific Leadership Council of the Coalition of Cancer Cooperative Groups
J. Clin. Oncol., June 1, 2007; 25(16): 2313 - 2321.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
K. M. Darcy, C. Tian, and E. Reed
A Gynecologic Oncology Group Study of Platinum-DNA Adducts and Excision Repair Cross-Complementation Group 1 Expression in Optimal, Stage III Epithelial Ovarian Cancer Treated with Platinum-Taxane Chemotherapy
Cancer Res., May 1, 2007; 67(9): 4474 - 4481.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
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]

Home page
 Ann OncolHome page
H-C Kwon, M. Roh, S. Oh, S-H Kim, M. Kim, J-S Kim, and H-J Kim
Prognostic value of expression of ERCC1, thymidylate synthase, and glutathione S-transferase P1 for 5-fluorouracil/oxaliplatin chemotherapy in advanced gastric cancer
Ann. Onc., March 1, 2007; 18(3): 504 - 509.
[Abstract] [Full Text] [PDF]

Home page
 Ann OncolHome page
J Bellmunt, L Paz-Ares, M Cuello, F. Cecere, S Albiol, V Guillem, E Gallardo, J Carles, P Mendez, J. de la Cruz, et al.
Gene expression of ERCC1 as a novel prognostic marker in advanced bladder cancer patients receiving cisplatin-based chemotherapy
Ann. Onc., March 1, 2007; 18(3): 522 - 528.
[Abstract] [Full Text] [PDF]

Home page
 Ann OncolHome page
P Ceppi, M Volante, S Novello, I Rapa, K. Danenberg, P. Danenberg, A Cambieri, G Selvaggi, S Saviozzi, R Calogero, et al.
ERCC1 and RRM1 gene expressions but not EGFR are predictive of shorter survival in advanced non-small-cell lung cancer treated with cisplatin and gemcitabine
Ann. Onc., December 1, 2006; 17(12): 1818 - 1825.
[Abstract] [Full Text] [PDF]

Home page
 Ann. Surg. Oncol.Home page
K. W. Suh, J. H. Kim, D. Y. Kim, Y. B. Kim, C. Lee, and S. Choi
Which Gene is a Dominant Predictor of Response During FOLFOX Chemotherapy for the Treatment of Metastatic Colorectal Cancer, the MTHFR or XRCC1 Gene?
Ann. Surg. Oncol., November 1, 2006; 13(11): 1379 - 1385.
[Abstract] [Full Text] [PDF]

Home page
 NEJMHome page
K. A. Olaussen, A. Dunant, P. Fouret, E. Brambilla, F. Andre, V. Haddad, E. Taranchon, M. Filipits, R. Pirker, H. H. Popper, et al.
DNA repair by ERCC1 in non-small-cell lung cancer and cisplatin-based adjuvant chemotherapy.
N. Engl. J. Med., September 7, 2006; 355(10): 983 - 991.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
F. A. Sinicrope, R. L. Rego, K. C. Halling, N. R. Foster, D. J. Sargent, B. La Plant, A. J. French, C. J. Allegra, J. A. Laurie, R. M. Goldberg, et al.
Thymidylate synthase expression in colon carcinomas with microsatellite instability.
Clin. Cancer Res., May 1, 2006; 12(9): 2738 - 2744.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
V. Garcia, J. M. Garcia, C. Pena, J. Silva, G. Dominguez, A. Hurtado, I. Alonso, R. Rodriguez, M. Provencio, and F. Bonilla
Thymidylate synthase messenger RNA expression in plasma from patients with colon cancer: prognostic potential.
Clin. Cancer Res., April 1, 2006; 12(7): 2095 - 2100.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
N. E. Kemeny, D. Niedzwiecki, D. R. Hollis, H.-J. Lenz, R. S. Warren, M. J. Naughton, J. C. Weeks, E. R. Sigurdson, J. E. Herndon II, C. Zhang, et al.
Hepatic Arterial Infusion Versus Systemic Therapy for Hepatic Metastases From Colorectal Cancer: A Randomized Trial of Efficacy, Quality of Life, and Molecular Markers (CALGB 9481)
J. Clin. Oncol., March 20, 2006; 24(9): 1395 - 1403.
[Abstract] [Full Text] [PDF]

Home page
 Ann OncolHome page
C. H. Smorenburg, G. J. Peters, C. J. van Groeningen, P. Noordhuis, K. Smid, A. M. G. H. van Riel, W. Dercksen, H. M. Pinedo, and G. Giaccone
Phase II study of tailored chemotherapy for advanced colorectal cancer with either 5-fluouracil and leucovorin or oxaliplatin and irinotecan based on the expression of thymidylate synthase and dihydropyrimidine dehydrogenase
Ann. Onc., January 1, 2006; 17(1): 35 - 42.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
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]

Home page
 Clin. Cancer Res.Home page
J. Viguier, V. Boige, C. Miquel, M. Pocard, B. Giraudeau, J.-C. Sabourin, M. Ducreux, A. Sarasin, and F. Praz
ERCC1 Codon 118 Polymorphism Is a Predictive Factor for the Tumor Response to Oxaliplatin/5-Fluorouracil Combination Chemotherapy in Patients with Advanced Colorectal Cancer
Clin. Cancer Res., September 1, 2005; 11(17): 6212 - 6217.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
W. L. Allen and P. G. Johnston
Role of Genomic Markers in Colorectal Cancer Treatment
J. Clin. Oncol., July 10, 2005; 23(20): 4545 - 4552.
[Abstract] [Full Text] [PDF]

Home page
 ChestHome page
G. R. Simon, S. Sharma, A. Cantor, P. Smith, and G. Bepler
ERCC1 Expression Is a Predictor of Survival in Resected Patients With Non-small Cell Lung Cancer
Chest, March 1, 2005; 127(3): 978 - 983.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
J. Yu, W. D. Shannon, M. A. Watson, and H. L. McLeod
Gene Expression Profiling of the Irinotecan Pathway in Colorectal Cancer
Clin. Cancer Res., March 1, 2005; 11(5): 2053 - 2062.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
R. Suk, S. Gurubhagavatula, S. Park, W. Zhou, L. Su, T. J. Lynch, J. C. Wain, D. Neuberg, G. Liu, and D. C. Christiani
Polymorphisms in ERCC1 and Grade 3 or 4 Toxicity in Non-Small Cell Lung Cancer Patients
Clin. Cancer Res., February 15, 2005; 11(4): 1534 - 1538.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
T. Lecomte, J.-M. Ferraz, F. Zinzindohoue, M.-A. Loriot, D.-A. Tregouet, B. Landi, A. Berger, P.-H. Cugnenc, R. Jian, P. Beaune, et al.
Thymidylate Synthase Gene Polymorphism Predicts Toxicity in Colorectal Cancer Patients Receiving 5-Fluorouracil-based Chemotherapy
Clin. Cancer Res., September 1, 2004; 10(17): 5880 - 5888.
[Abstract] [Full Text] [PDF]

Home page
 Ann OncolHome page
D. Isla, C. Sarries, R. Rosell, G. Alonso, M. Domine, M. Taron, G. Lopez-Vivanco, C. Camps, M. Botia, L. Nunez, et al.
Single nucleotide polymorphisms and outcome in docetaxel-cisplatin-treated advanced non-small-cell lung cancer
Ann. Onc., August 1, 2004; 15(8): 1194 - 1203.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
W. Zhou, S. Gurubhagavatula, G. Liu, S. Park, D. S. Neuberg, J. C. Wain, T. J. Lynch, L. Su, and D. C. Christiani
Excision Repair Cross-Complementation Group 1 Polymorphism Predicts Overall Survival in Advanced Non-Small Cell Lung Cancer Patients Treated With Platinum-Based Chemotherapy
Clin. Cancer Res., August 1, 2004; 10(15): 4939 - 4943.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
C.-K. Youn, M.-H. Kim, H.-J. Cho, H.-B. Kim, I.-Y. Chang, M.-H. Chung, and H. J. You
Oncogenic H-Ras Up-Regulates Expression of ERCC1 to Protect Cells from Platinum-Based Anticancer Agents
Cancer Res., July 15, 2004; 64(14): 4849 - 4857.
[Abstract] [Full Text] [PDF]

Home page
 Ann OncolHome page
R. Chan and D. J. Kerr
Can we individualise chemotherapy for colorectal cancer?
Ann. Onc., July 1, 2004; 15(7): 996 - 999.
[Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
U. Warnecke-Eberz, R. Metzger, F. Miyazono, S. E. Baldus, S. Neiss, J. Brabender, H. Schaefer, W. Doerfler, E. Bollschweiler, H. P. Dienes, et al.
High Specificity of Quantitative Excision Repair Cross-Complementing 1 Messenger RNA Expression for Prediction of Minor Histopathological Response to Neoadjuvant Radiochemotherapy in Esophageal Cancer
Clin. Cancer Res., June 1, 2004; 10(11): 3794 - 3799.
[Abstract] [Full Text] [PDF]

Home page
 JAMAHome page
R. K. Hasan, J. D. Wulfkuhle, L. A. Liotta, and E. F Petricoin
Molecular Technologies for Personalized Cancer Management
JAMA, April 7, 2004; 291(13): 1644 - 1645.
[Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
J. Boyer, E. G. McLean, S. Aroori, P. Wilson, A. McCulla, P. D. Carey, D. B. Longley, and P. G. Johnston
Characterization of p53 Wild-Type and Null Isogenic Colorectal Cancer Cell Lines Resistant to 5-Fluorouracil, Oxaliplatin, and Irinotecan
Clin. Cancer Res., March 15, 2004; 10(6): 2158 - 2167.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
S. Popat, A. Matakidou, and R. S. Houlston
Thymidylate Synthase Expression and Prognosis in Colorectal Cancer: A Systematic Review and Meta-Analysis
J. Clin. Oncol., February 1, 2004; 22(3): 529 - 536.
[Abstract] [Full Text] [PDF]

Home page
 Molecular Cancer TherapeuticsHome page
R. L. Hayward, J. S. Macpherson, J. Cummings, B. P. Monia, J. F. Smyth, and D. I. Jodrell
Enhanced oxaliplatin-induced apoptosis following antisense Bcl-xl down-regulation is p53 and Bax dependent: Genetic evidence for specificity of the antisense effect
Mol. Cancer Ther., February 1, 2004; 3(2): 169 - 178.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
K. Uchida, K. Hayashi, K. Kawakami, S. Schneider, J. M. Yochim, H. Kuramochi, K. Takasaki, K. D. Danenberg, and P. V. Danenberg
Loss of Heterozygosity at the Thymidylate Synthase (TS) Locus on Chromosome 18 Affects Tumor Response and Survival in Individuals Heterozygous for a 28-bp Polymorphism in the TS Gene
Clin. Cancer Res., January 15, 2004; 10(2): 433 - 439.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
A. Vekris, D. Meynard, M.-C. Haaz, M. Bayssas, J. Bonnet, and J. Robert
Molecular Determinants of the Cytotoxicity of Platinum Compounds: The Contribution of in Silico Research
Cancer Res., January 1, 2004; 64(1): 356 - 362.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
E. Reed, J. J. Yu, A. Davies, J. Gannon, and S. L. Armentrout
Clear Cell Tumors Have Higher mRNA Levels of ERCC1 and XPB Than Other Histological Types of Epithelial Ovarian Cancer
Clin. Cancer Res., November 1, 2003; 9(14): 5299 - 5305.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
J. Yu, S. Marsh, R. Ahluwalia, and H. L. McLeod
Ferredoxin Reductase: Pharmacogenomic Assessment in Colorectal Cancer
Cancer Res., October 1, 2003; 63(19): 6170 - 6173.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
M. Gonen, A. Hummer, A. Zervoudakis, D. Sullivan, Y. Fong, D. Banerjee, D. Klimstra, C. Cordon-Cardo, J. Bertino, and N. Kemeny
Thymidylate Synthase Expression in Hepatic Tumors Is a Predictor of Survival and Progression in Patients With Resectable Metastatic Colorectal Cancer
J. Clin. Oncol., February 1, 2003; 21(3): 406 - 412.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
W. Ichikawa, H. Uetake, Y. Shirota, H. Yamada, N. Nishi, Z. Nihei, K. Sugihara, and R. Hirayama
Combination of Dihydropyrimidine Dehydrogenase and Thymidylate Synthase Gene Expressions in Primary Tumors as Predictive Parameters for the Efficacy of Fluoropyrimidine-based Chemotherapy for Metastatic Colorectal Cancer
Clin. Cancer Res., February 1, 2003; 9(2): 786 - 791.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
R. V. N. Lord, J. Brabender, D. Gandara, V. Alberola, C. Camps, M. Domine, F. Cardenal, J. M. Sanchez, P. H. Gumerlock, M. Taron, et al.
Low ERCC1 Expression Correlates with Prolonged Survival after Cisplatin plus Gemcitabine Chemotherapy in Non-Small Cell Lung Cancer
Clin. Cancer Res., July 1, 2002; 8(7): 2286 - 2291.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
M.-C. Etienne, M. Chazal, P. Laurent-Puig, N. Magne, C. Rosty, J.-L. Formento, M. Francoual, P. Formento, N. Renee, E. Chamorey, et al.
Prognostic Value of Tumoral Thymidylate Synthase and p53 in Metastatic Colorectal Cancer Patients Receiving Fluorouracil-Based Chemotherapy: Phenotypic and Genotypic Analyses
J. Clin. Oncol., June 15, 2002; 20(12): 2832 - 2843.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
J. S. Macdonald
Vive La Difference: Sex and Fluorouracil Toxicity
J. Clin. Oncol., March 15, 2002; 20(6): 1439 - 1441.
[Full Text] [PDF]


About
JCO		 Editorial
Roster		 Advertising
Information		 Librarians &
Institutions		 Rights &
Permissions		 Site Map

Copyright © 2001 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
Terms and Conditions of Use
  HighWire Press HighWire Press™ assists in the publication of JCO Online