Fluorescence Bronchoscopy and Molecular Characterization of Abnormal Bronchial Lesions: Novel Approaches for Early Detection of Lung Cancer in High Risk Patients

Despite intensive research efforts, there are still no simple and effective screening tools to detect early lung cancer. The majority of newly diagnosed patients have higher stage, often disseminated, non-resectable disease. A better understanding of the natural biology and molecular abnormalities in early lung lesions may aid in the development of more effective screening tools. This study will investigate the effectiveness of bronchoscopy by white light (WL) alone and in combination with Lung Imaging Fluorescence Endoscopy (LIFE) for the detection of early lung lesions in patients with a high risk for developing lung cancer. LIFE is a FDA approved adjunct to WL bronchoscopy for the screening of lung cancer and this study will provide a standardized setting in which a direct comparison between a combination of WL and LIFE versus traditional WL bronchoscopy can be made.

In addition, the study will set the stage for the collection of a unique set of biopsy specimens that will be used to learn more about the natural biology and the molecular changes in early lung lesions. We will study abnormalities in p53 by immunohistochemistry and by molecular analyses. The p53 results will be compared with histological grade and with genomic instability. Measures for genomic instability will be the loss of chromosomal information and cellular aneuploidy. Recent advances in molecular pathology, such as the development of Laser Capture Microdissection (LCM), have made the molecular profiling of these extremely small lesions feasible. The information obtained by these techniques will be used for comparison with clinical and exposure information. Future plans include the culturing of bronchial epithelial cells to study genomic instability in the multistep process of cancer progression. It is our hope that the application of these new technologies will improve the early detection of human lung cancer and provide insight into the natural biology and molecular changes of early lung lesions which may progress towards overt cancers.

Despite intensive research efforts, there are still no simple and effective screening tools to detect early lung cancer. The majority of newly diagnosed patients have higher stage, often disseminated, non-resectable disease. A better understanding of the natural biology and molecular abnormalities in early lung lesions may aid in the development of more effective screening tools. The Lung Imaging Fluorescence Endoscopy (LIFE) is FDA approved as an adjunct to WL bronchoscopy for the screening of lung cancer.

Using the LIFE unit, this study will set the stage for the collection of a unique set of biopsy specimens that will be used to learn more about the natural biology and molecular changes in early lung lesions. We will study abnormalities in p53 by immunohistochemistry and by molecular analyses. The p53 results will be compared with histological grade and with genomic instability. Measures for genomic instability will be the loss of chromosomal information and cellular aneuploidy. Recent advances in molecular pathology, such as the development of Laser Capture Microdissection (LCM), have made the molecular profiling of these extremely small lesions feasible. The information obtained by these techniques will be used for comparison with clinical and exposure information. Future plans include the culturing of bronchial epithelial cells to study genomic instability in the multistep process of cancer progression. It is our hope that the application of these new technologies will improve the early detection of human lung cancer and provide insight into the natural biology and molecular changes of early lung lesions which may progress towards overt cancers.

Eligibility Criteria:
* INCLUSION CRITERIA:

Previously resected stage I, II and IIIa lung cancers.

Prior head and neck carcinoma.

Bronchogenic carcinoma in a first degree relative.

Smoking history of more than 15 pack-years current or past.

Previously treated for Hodgkin's Disease.

Abnormal sputum cytology with negative radiographs.

EXCLUSION CRITERIA:

Patients with a current clinically detectable lung cancer.

Age lower than 35 years.

Pregnant or possibly pregnant.

Patients with any contraindications to bronchoscopy.

Severe underlying medical conditions such as unstable angina, uncompensated congestive heart failure, severe airway obstruction (FEV1) less than 0.8 L), or uncontrolled hypertension.

Patients with a bleeding disorder or patients on anticoagulant therapy.

Use of chemopreventive drugs (retinoids) or photosensitizing agents (hematoporphyrin derivatives) within 3 months prior to initial bronchoscopy.

Life expectancy less than 3 months.

Patients who received chemotherapy or radiotherapy within 6 months prior to initial bronchoscopy.