Detection of morphological and genetic changes of the bronchial mucosa by autofluorescence bronchoscopy in heavy smokers
Abstract
The aim of the study was to estimate morphological and genetic changes of the bronchial mucosa in relation to autofluorescence bronchoscopy (AFB) findings, and to evaluate the benefit of the method for detection of early bronchogenic carcinoma in a high-risk population. 232 smokers with cigarette exposure higher than 30 pack-years and with FEV1 lower than 70 % of the predicted value, scheduled for bronchoscopy as a part of their standard diagnostic work up, were enrolled in the study. AFB with the Onco-LIFE system was performed following standard white light bronchoscopy (WLB).
Biopsies were taken from positive or suspicious areas in WLB or AFB and also from areas vrith normal appearance. The samples were examined by histological and molecular genetic methods.
From a total of 474 biopsies, 398 were suitable for analysis. Normal bronchial mucosa, inflammation, hyperplasia/squamous metaplasia or mild dysplasia were found in 309 (77.6 %) biopsies, which were classified as negative.
The 89 (22.4 %) positive biopsies included 24 moderate/severe dysplasias, 7 carcinomas in-situ, one microinvasive carcinoma and 57 invasive carcinomas. The overall histology-based sensitivity and specificity values after excluding invasive carcinoma were 31.3 % and 91.6 % for WLB and 34.4 % and 80.3 % for AFB, respectively.
The lower specificity of AFB was statistically significant. In detecting premalignant changes, AFB was not more effective than WLB.
Molecular assessment of histologically negative samples (n = 97) demonstrated a significantly higher incidence of loss of heterozygosity (LOH) in the mismatch repair gene region on the short arm of chromosome 3 (D3S1611) and in one locus in the tumour suppressor gene region of chromosome 9 (D9S259), and higher expression of mRNA telomerase subunit hTERT in biopsies from sites positive in AFB than in randomly sampled biopsies, suggesting higher sensitivity of AFB in detection of early stages of Ccircinogenesis in comparison with standard histology. According to our results, AFB is not effective for the detection of histologically proven preneoplastic changes. but it is useful in detecting earlier stages of carcinogenesis manifested only by genetic alterations.