PURPOSE: The outcome of precancerous bronchial lesions is not well known, and their management is subject to controversy. Many molecular alterations are present in preinvasive lesions, but no one has been assessed to predict the evolution of the lesion. The purpose of this study was to analyze the outcome of high grade precancerous lesions according to their molecular profile.
METHODS: 21 severe dysplasia and 27 carcinoma in situ (CIS) in 33 patients were followed-up using repeated autofluorescence bronchoscopy over a 11 years period. Microdissection and PCR analysis were performed on the paraffin tissue sections to assess loss of heterozygosity (LOH) and microsatellite instability on chromosome 3p, 5q, and 9p. Histology and molecular status at baseline were compared between the progressing, stable and regressing lesions.
RESULTS: The median follow-up was 65 months. Among 14 lesions that progressed 13 were CIS, whereas 35% of stable and 82% of regressing lesions were severe dysplasia (p=0,0001). 3p and 9p LOH were more frequent in CIS than in severe dysplasia (p=0,02). In the whole group of lesions, 3p LOH, or at least one LOH were strongly associated with progression (p=0,0002, and p=0.03, respectively). 5q LOH and microsatellite instability were not associated with the outcome of the lesions. A therapeutic strategy based on the presence of 3p or 9p LOH, would have led to overtreat 4 lesions but would have missed only one among the 14 progressing lesions.
CONCLUSION: Baseline histology and 3p and 9p LOH analysis appear to be useful to predict the outcome of high grade precancerous lesions.
CLINICAL IMPLICATIONS: Our data suggest the possible use of a simple, 3p and 9p LOH based management decision tree of high grade precancerous lesions.
DISCLOSURE: Mathieu Salaun, No Financial Disclosure Information; No Product/Research Disclosure Information