Role and prognostic significance of tumor necrosis factor-related apoptosis-inducing ligand death receptor DR5 in nonsmall-cell lung cancer and precursor lesions

Authors

  • Wendy A. Cooper MBBS, BSc(Med),

    Corresponding author
    1. Department of Anatomical Pathology, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia
    • Department of Anatomical Pathology, Royal Prince Alfred Hospital, Missenden Rd., Camperdown NSW 2050 Australia
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    • Fax: (011) 61-2-9515-8405

  • Maija R.J. Kohonen-Corish PhD,

    1. Cancer Research Program, Garvan Institute of Medical Research and St Vincent's Clinical School, Faculty of Medicine, University of New South Wales, Sydney, New South Wales, Australia
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    • M.K.-C. is a Cancer Institute New South Wales Fellow.

  • Liqing Zhuang MD,

    1. Department of Anatomical Pathology, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia
    2. Discipline of Pathology, Faculty of Medicine, University of Sydney, Sydney, New South Wales, Australia
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  • Brian McCaughan MBBS,

    1. Department of Cardiothoracic Surgery, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia
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  • Catherine Kennedy,

    1. Strathfield Private Hospital, Sydney, New South Wales, Australia
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  • Gavin Screaton BMBCh, MRCP, DPhil,

    1. Imperial College, Royal Postgraduate Medical School, Hammersmith Hospital, London, United Kingdom
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  • Robert L. Sutherland PhD,

    1. Cancer Research Program, Garvan Institute of Medical Research and St Vincent's Clinical School, Faculty of Medicine, University of New South Wales, Sydney, New South Wales, Australia
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  • C-Soon Lee MD

    1. Discipline of Pathology, Faculty of Medicine, University of Sydney, Sydney, New South Wales, Australia
    2. Bosch Institute and Central Clinical School, University of Sydney, Sydney, New South Wales, Australia
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Abstract

BACKGROUND.

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).

METHODS.

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.

RESULTS.

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.

CONCLUSIONS.

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.

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