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Role and prognostic significance of tumor necrosis factor-related apoptosis-inducing ligand death receptor DR5 in nonsmall-cell lung cancer and precursor lesions
Article first published online: 5 MAY 2008
Copyright © 2008 American Cancer Society
Volume 113, Issue 1, pages 135–142, 1 July 2008
How to Cite
Cooper, W. A., Kohonen-Corish, M. R.J., Zhuang, L., McCaughan, B., Kennedy, C., Screaton, G., Sutherland, R. L. and Lee, C.-S. (2008), Role and prognostic significance of tumor necrosis factor-related apoptosis-inducing ligand death receptor DR5 in nonsmall-cell lung cancer and precursor lesions. Cancer, 113: 135–142. doi: 10.1002/cncr.23528
- Issue published online: 20 JUN 2008
- Article first published online: 5 MAY 2008
- Manuscript Accepted: 13 FEB 2008
- Manuscript Revised: 7 FEB 2008
- Manuscript Received: 17 DEC 2007
- United Kingdom Medical Research Council
- Cancer Institute NSW
- National Health and Medical Research Council
- R. T. Hall Trust
- nonsmall cell lung carcinoma;
- TRAIL receptor;
The tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) death receptor, DR5, mediates proapoptotic signals and is implicated in the pathogenesis of many neoplasms including nonsmall-cell lung cancer (NSCLC).
In this study, immunohistochemical expression of DR5 was examined in 146 cases of stage I and II NSCLC as well as neoplastic precursor lesions and regional lymph node metastases using tissue microarrays.
High DR5 expression was observed in 67.1% of primary NSCLC, 55.6% of bronchial squamous carcinoma in situ, 40% of squamous metaplasia, as well as 76.5% of lymph node metastases. In all of these lesions, DR5 expression was significantly higher than in normal bronchial epithelium. Increased expression of DR5 correlated with poorly differentiated tumors and was inversely correlated with bronchioloalveolar carcinomas. There was no correlation with other clinicopathologic variables. A significant association was found between high DR5 expression and reduced overall survival in univariate analysis. Among smokers, high DR5 and tumor stage were independent predictors of reduced disease-free survival in multivariate analysis, however, DR5 was not an independent prognostic marker among the entire cohort of NSCLC.
These findings suggest that DR5 plays a role in the development of early-stage NSCLC and the high levels of DR5 expression suggest that these tumors may be susceptible to novel anticancer agents targeting the DR5 receptor and may improve patient survival, particularly for patients who are smokers. Cancer 2008. ©2008 American Cancer Society.