Abstract CN07-03: Natural history of bronchial preneoplasia

Abstract

Abstract Preinvasive bronchial lesions defined as dysplasia and carcinoma in-situ (CIS) have been considered as precursors of squamous cell carcinoma of the lung. The risk and rate of progression of preinvasive lesions to invasive squamous cell carcinoma as well as the mechanism of progression or regression are incompletely understood. The evidence for the multistage, stepwise progression model is weak with relatively few documented lesions that progress through normal to hyperplasia, metaplasia and various grades of dysplasia to CIS and then to invasive carcinoma. Collective data from longitudinal studies using autofluorescence bronchoscopy directed sequential bronchial biopsies from the Netherlands, Canada, France, and Japan as well as published data suggest that the time to development of CIS or invasive squamous cell carcinoma from precursor lesions does not follow an anticipated trend from a stepwise progression model. Aside from severe dysplasia that has the shortest progression time, there is no pattern between the baseline pathology and the time of development of CIS or invasive cancer. The presence of dyspalsia or CIS is a field cancerization risk marker for lung cancer both in the central airways and peripheral lung. Specific genetic alterations and host factors such as the inflammatory load and levels of anti-inflammatory proteins in the lung likely influence the progression or regression of pre-invasive lesions. Recently, using integrative genomic approach, combining high-resolution comparative genomic hybridization and gene expression microarray profiles, the focal amplification of an oncogene -BRF2 in chromosome region 8p12 was found to be specific for development of lung squamous cell carcinoma through the increase of Pol III mediated transcription. BRF2 was frequently activated in carcinoma in situ and dysplasia (PLoS Med 7(7): e1000315. doi:10.1371/journal.pmed.1000315). Molecular analysis of rare lesions that progress from normal, hyperplasia, metaplasia or dysplasia to CIS or invasive cancer will shed further light on the key molecular determinants driving development to an invasive phenotype versus those associated with tobacco smoke damage. Citation Information: Cancer Prev Res 2010;3(12 Suppl):CN07-03.