FREE NEJM E-TOC    HOME   |   SUBSCRIBE   |   CURRENT ISSUE   |   PAST ISSUES   |   COLLECTIONS   |   Search Term  Advanced Search

Sign in | Get NEJM's E-Mail Table of Contents — Free | Subscribe

Previous Volume 356:800-808 February 22, 2007 Number 8 Next

	Full Text PDF PDA Full Text PowerPoint Slide Set Supplementary Material Perspective by Gazdar, A. F. Letters Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited E-mail When Letters Appear PubMed Citation

ABSTRACT

Background RRM1, the regulatory subunit of ribonucleotide reductase, is involved in carcinogenesis, tumor progression, and the response of non–small-cell lung cancer to treatment.

Methods We developed an automated quantitative determination of the RRM1 protein in routinely processed histologic specimens. In these specimens, we measured the expression of RRM1 and two other proteins that are relevant to non–small-cell lung cancer: the excision repair cross-complementation group 1 (ERCC1) protein and the phosphatase and tensin homologue (PTEN). We compared the results with the clinical outcomes in 187 patients with early-stage non–small-cell lung cancer who had received only surgical treatment.

Results RRM1 expression correlated with the expression of ERCC1 (P<0.001) but not with the expression of PTEN (P=0.37). The median disease-free survival exceeded 120 months in the group of patients with tumors that had high expression of RRM1 and was 54.5 months in the group with low expression of RRM1 (hazard ratio for disease progression or death in the high-expression group, 0.46; P=0.004). The overall survival was more than 120 months for patients with tumors with high expression of RRM1 and 60.2 months for those with low expression of RRM1 (hazard ratio for death, 0.61; P=0.02). Among these 187 patients, the survival advantage was limited to the 30% of patients with tumors that had a high expression of both RRM1 and ERCC1.

Conclusions RRM1 and ERCC1 are determinants of survival after surgical treatment of early-stage, non–small-cell lung cancer.

Source Information

From the Division of Thoracic Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL.

Address reprint requests to Dr. Bepler at the H. Lee Moffitt Cancer Center and Research Institute, MRC-4W, Rm. 4046, 12902 Magnolia Dr., Tampa, FL 33612-9497, or at beplerg{at}moffitt.usf.edu.

Full Text of this Article

Related Letters:

ERCC1 and Non–Small-Cell Lung Cancer
Niedernhofer L. J., Bhagwat N., Wood R. D., Zhou S.-F., Panasci L., Cohen V., Bepler G., Zheng Z., Chen T.
Extract | Full Text | PDF  
N Engl J Med 2007; 356:2538-2541, Jun 14, 2007. Correspondence

This article has been cited by other articles:

• Einhorn, L. H. (2008). First-Line Chemotherapy for Non-Small-Cell Lung Cancer: Is There a Superior Regimen Based on Histology?. JCO 26: 3485-3486 [Full Text]  
• Kim, M. K., Cho, K.-J., Kwon, G. Y., Park, S.-I., Kim, Y. H., Kim, J. H., Song, H.-Y., Shin, J. H., Jung, H. Y., Lee, G. H., Choi, K. D., Kim, S.-B. (2008). Patients with ERCC1-Negative Locally Advanced Esophageal Cancers May Benefit from Preoperative Chemoradiotherapy. Clin. Cancer Res. 14: 4225-4231 [Abstract] [Full Text]  
• Khuri, F. R., Roman, J. (2008). From Nihilism to Individualism: The Evolution of Lung Cancer Therapy. Am. J. Respir. Crit. Care Med. 177: 1299-1300 [Full Text]  
• Kim, S.-O., Jeong, J.-Y., Kim, M.-R., Cho, H.-J., Ju, J.-Y., Kwon, Y.-S., Oh, I.-J., Kim, K.-S., Kim, Y.-I., Lim, S.-C., Kim, Y.-C. (2008). Efficacy of Gemcitabine in Patients with Non-Small Cell Lung Cancer According to Promoter Polymorphisms of the Ribonucleotide Reductase M1 Gene. Clin. Cancer Res. 14: 3083-3088 [Abstract] [Full Text]  
• Breen, D., Barlesi, F. (2008). The place of excision repair cross complementation 1 (ERCC1) in surgically treated non-small cell lung cancer. Eur. J. Cardiothorac. Surg. 33: 805-811 [Abstract] [Full Text]  
• Yu, D., Zhang, X., Liu, J., Yuan, P., Tan, W., Guo, Y., Sun, T., Zhao, D., Yang, M., Liu, J., Xu, B., Lin, D. (2008). Characterization of Functional Excision Repair Cross-Complementation Group 1 Variants and Their Association with Lung Cancer Risk and Prognosis. Clin. Cancer Res. 14: 2878-2886 [Abstract] [Full Text]  
• Xu, X., Page, J. L., Surtees, J. A., Liu, H., Lagedrost, S., Lu, Y., Bronson, R., Alani, E., Nikitin, A. Yu., Weiss, R. S. (2008). Broad Overexpression of Ribonucleotide Reductase Genes in Mice Specifically Induces Lung Neoplasms. Cancer Res. 68: 2652-2660 [Abstract] [Full Text]  
• Sun, Z., Wigle, D. A., Yang, P. (2008). Non-Overlapping and Non-Cell-Type-Specific Gene Expression Signatures Predict Lung Cancer Survival. JCO 26: 877-883 [Abstract] [Full Text]  
• Olaussen, K. A., Fouret, P., Kroemer, G. (2007). ERCC1-Specific Immunostaining in Non-Small-Cell Lung Cancer. NEJM 357: 1559-1561 [Full Text]  
• Soria, J.-C. (2007). ERCC1-Tailored Chemotherapy in Lung Cancer: The First Prospective Randomized Trial. JCO 25: 2648-2649 [Full Text]  
• Simon, G., Sharma, A., Li, X., Hazelton, T., Walsh, F., Williams, C., Chiappori, A., Haura, E., Tanvetyanon, T., Antonia, S., Cantor, A., Bepler, G. (2007). Feasibility and Efficacy of Molecular Analysis-Directed Individualized Therapy in Advanced Non-Small-Cell Lung Cancer. JCO 25: 2741-2746 [Abstract] [Full Text]  
• Niedernhofer, L. J., Bhagwat, N., Wood, R. D., Zhou, S.-F., Panasci, L., Cohen, V., Bepler, G., Zheng, Z., Chen, T. (2007). ERCC1 and Non-Small-Cell Lung Cancer. NEJM 356: 2538-2541 [Full Text]  
• Cosgrove, J. (2007). Using molecular markers as a means of predicting prognosis and outcomes in the treatment of lung cancer. Thorax 62: 535-535 [Full Text]