p53 and chromosome 3 abnormalities, characteristic of malignant lung tumours, are detectable in preinvasive lesions of the bronchus.
Bronchial epithelial dysplasia is believed to precede invasive squamous cell carcinoma of the lung. Six paired dysplasia and tumour samples were distinguished histologically in sections of formalin-fixed paraffin-embedded lung tissue from patients with lung cancer. Additionally, samples of dysplastic bronchial epithelium were obtained from patients without lung tumours. Microdissection of the unstained sections provided dysplastic and tumour samples from which DNA was prepared for comparison with the patients' constitutional genotype, using polymerase chain reaction-based restriction fragment length polymorphism analysis. All six samples of tumour and the paired adjacent samples of bronchial dysplasia showed loss of heterozygosity (LOH) at loci on the short arm of chromosome 3. Five of the six cases showed involvement of the p53 gene as assessed by LOH at the AccII site within the gene, and by immunoreactivity to CM-1, an antibody which recognizes the mutated form of the p53 protein in paraffin-embedded material. Of the dysplastic samples, obtained from patients without invasive tumours, all three showed LOH at 3p; one sample showed LOH at the AccII polymorphic locus within the p53 gene, and another sample, uninformative at this locus, stained positively with this antibody. These results indicate that somatic genetic changes are present in preinvasive lesions in the bronchus.
Sundaresan
V
V
Medical Research Council, Clinical Oncology and Radiotherapeutics Unit, Cambridge, UK.
Ganly
P
P
Hasleton
P
P
Rudd
R
R
Sinha
G
G
Bleehen
N M
NM
Rabbitts
P
P
D001483:Base Sequence; D001980:Bronchi / Q000473:pathology* / Q000648:ultrastructure; D002869:Chromosome Aberrations; D002893:Chromosomes, Human, Pair 3; D016158:Genes, p53; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D008969:Molecular Sequence Data; D009154:Mutation; D010641:Phenotype; D011230:Precancerous Conditions / Q000235:genetics*