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Role of biomarkers for early detection of lung cancer and chemoprevention

¹ Dept of Pathology, University of Colorado Health Sciences Centre and ² Dept of Pathology, Denver Veterans Administration Medical Centre, Denver, USA

CORRESPONDENCE: F.R. Hirsch, University of Colorado Cancer Center, Dept of Pathology, University of Colorado Health Sciences Center, 4200 East Ninth Avenue, B216 Denver, CO 80262. Fax: 30 31511835. E-mail: Fred.Hirsch@UCHSC.edu

Keywords: early detection, lung cancer, molecular biology, pathology, review

Received: November 8, 2001
Accepted January 23, 2002

This study was supported by National Cancer Institute Grants CA 58187 from the Specialized Programme of Research Excellence (SPORE)-Lung and the Lung Cancer Biomarkers and Chemoprevention Consortium, by a Career Development Grant for F.R. Hirsch from The International Association for the Study of Lung Cancer/Cancer Research Foundation of America and by a seed grant from the Colorado SPORE-Lung Programme to D.T. Merrick.

Abstract

Lung cancer is the leading cause of cancer deaths in developed countries. The poor prognosis associated with this disease is closely related to the fact that most lung cancer patients are not identified until their malignancy has reached an advanced stage.

Recent advances have added to the understanding of the morphological and molecular characteristics of preinvasive bronchial lesions and early lung cancers. Such information is being used to provide new tests for the detection of lung cancer at early or preinvasive stages, and for identifying targets for therapeutic intervention that can prevent progression to advanced disease. Laser induced fluorescence endoscope bronchoscopy has improved the sensitivity with which preinvasive dysplastic bronchial lesions and early invasive malignancies can be detected. Morphological features of such lesions have been described and can be monitored by follow-up bronchoscopies in order to validate potential chemoprevention treatments.

Distinct morphological characteristics such as angiogenic squamous dysplasia also suggest that processes like angiogenesis are present early in the development of lung cancer. Furthermore, tissue obtained from these early lesions has been used to describe alterations in the expression of a number of factors that distinguish these early lesions from normal bronchial epithelium. This could provide molecular markers and targets for the detection and treatment of early lung cancer. Studies to detect these alterations by polymerase chain reaction and/or immunhistochemical analyses of easily obtained specimens such as sputa are helping identifing molecular markers that could be utilized in effective screening programmes.

The current article reviews new findings regarding the molecular biology of preinvasive bronchial lesions and early lung cancers, and describes new developments regarding their application in the early detection and chemoprevention of lung cancer.

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