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Toxicologic Pathology
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Articles

Detection of Pre-Invasive Lung Cancer: Technical Aspects of the LIFE Project

Gordon P. Flake1, M. Patricia Rivera2, William K. Funkhouser2, Susan J. Maygarden2, Kellen L. Meadows3, Elizabeth H. Long4, Pat S. Stockton1, Tina C. Jones1, Hyeon Woo Yim3,7, Robbert J.C. Slebos5 and Jack A. Taylor3,6

1 Laboratory of Experimental Pathology, National Institute of Environmental Sciences, NIH, Research Triangle Park, NC 27709, USA
2 Multidisciplinary Thoracic Oncology Program, UNC Hospitals, Chapel Hill, NC 27514, USA
3 Laboratory of Molecular Carcinogenesis, National Institute of Environmental Sciences, NIH, Research Triangle Park, NC 27709, USA
4 Social and Scientific Systems, Incorporated, Durham, NC 27703, USA
5 Departments of Cancer Biology and Otolaryngology, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA
6 Epidemiology Branch, National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health (NIH), Department of Health and Human Services (DHHS), Research Triangle Park, NC 27709, USA

Correspondence: Address correspondence to: Dr. G. Flake, Laboratory of Experimental Pathology, National Institute of Environmental Health Sciences, P.O. Box 12233, MD B3-06, 111 T.W. Alexander Drive, Bldg. 101, Research Triangle Park, NC 27709, USA; e-mail:flake{at}niehs.nih.gov

Lung cancer is the leading cause of cancer deaths in both men and women in the United States. The LIFE (Light Induced Fluorescence Endoscopy) Project was initiated at the University of North Carolina Medical Center in November, 1999, for the dual purposes of (1) detecting pre-invasive lung cancer in high-risk patients and (2) studying the molecular biology of pre-invasive lesions of the bronchus for possible development of molecular biomarkers. Of the 47 patients enrolled, all were current or former tobacco smokers, except for 1. Fluorescence endoscopy was utilized, in addition to white light bronchoscopy, to increase the detection of intraepithelial lesions. Adjacent biopsies were submitted for permanent and frozen sections, respectively, from four predetermined sites as well as from any abnormal areas. The snap-frozen specimens were cryostat sectioned, and the mucosal epithelial cells laser capture microdissected for DNA analysis. The great majority of specimens yielded sufficiently abundant and intact DNA to accomplish the molecular objectives. Histologic concordance of adjacent permanent and frozen sections was equivalent to the concordance of adjacent permanent sections, suggesting that frozen section diagnosis was adequate for the research purpose of correlating histology with molecular analysis.

Key Words: Pre-invasive lung cancer • bronchial dysplasia • fluorescence endoscopy • frozen sections • laser capture microdissection

Toxicologic Pathology, Vol. 35, No. 1, 65-74 (2007)
DOI: 10.1080/01926230601052659


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