Molecular Mechanisms of Bronchial Dysplasia in High-Risk Patients

该方案旨在收集有关肺支气管粘膜癌细胞自然进展的信息。在与博士合作。富兰克林广场医院肺科和肿瘤科的William Krimsky和William McGuire，我们将接受在对空气消化系统恶性肿瘤高风险患者进行支气管镜筛查时获得的正常和病理活检标本。组织将使用标准的柔性支气管镜获得，该支气管镜包括带有相机单元的自动荧光支气管镜（AFB）系统。AFB用于检测肺支气管黏膜的恶性和癌前病变，其敏感性可达95%以上，经常检测到痰细胞学上未检出的病变（Lam et al ., 1993; Pasic et al ., 2003; Loewen et al ., 2006）。癌前和附近健康上皮的活检标本将被分开：一半将被送到富兰克林广场病理学系的布鲁萨德博士那里，另一半将被送到国家衰老研究所的凯文·贝克尔博士那里。基因表达谱分析将在正常和发育不良的标本上进行，以试图确定对支气管上皮内瘤变的发生和进展至关重要的分子途径。这是一项对来自20例患者的成对活检标本的初步研究，以确定从非常小的组织标本中获得可靠的GEP数据的可行性，并将GEP数据与每个标本的病理分类进行比较，以确定活检中的细胞异质性是否表明需要在未来的研究中结合激光捕获显微解剖。

This protocol is designed to gather information about the natural progression of cancerous cells in the bronchial mucosa of the lung. In collaboration with Drs. William Krimsky and William McGuire of the Franklin Square Hospital Pulmonary and Oncology Divisions, we will receive normal and pathologic biopsy specimens obtained during screening bronchoscopies performed in patients at high risk for aerodigestive malignancies. The tissue will be obtained using a standard flexible bronchoscope that includes an Autofluoescence Brochoscopy (AFB) system with a camera unit. AFB is used in to detect malignant and premalignant lesions in the bronchial mucosa of the lung and has been shown to have a sensitivity rate of over 95%, often detecting lesions that are missed on sputum cytology (Lam et al, 1993; Pasic et al, 2003; Loewen et al, 2006). Biopsy specimens from premalignant and nearby healthy epithelium will be divided: half will be sent to Dr. Broussard of Franklin Square Department of Pathology, and the remaining half will be delivered to Dr. Kevin Becker at the National Institute on Aging. Gene expression profiling will be performed on normal and dysplastic specimens in an attempt to identify molecular pathways that are important for the development and progression of bronchial intra-epithelial neoplasia. This is a pilot study of paired biopsy specimens from 20 patients to determine the feasibility of obtaining reliable GEP data from very small tissue specimens, and to compare GEP data with pathologic classification of each specimen to determine if cellular heterogeneity within biopsies indicates the need to incorporate laser capture microdissection in future studies.