title: Widely dispersed p53 mutation in respiratory epithelium. A novel mechanism for field carcinogenesis.
abstract: Individuals with one aerodigestive tract malignancy have a high incidence of second primary aerodigestive tumors. The mechanism for this field effect has not been determined. We studied an individual with widespread dysplastic changes in the respiratory epithelium but no overt carcinoma. The entire tracheobronchial tree obtained at autopsy was embedded in paraffin, and bronchial epithelial cells were isolated by microdissection. DNA extracted from the microdissected cells was analyzed for point mutations in the p53 tumor suppressor gene. A single, identical point mutation consisting of a G:C to T:A transversion in codon 245 was identified in bronchial epithelium from 7 of 10 sites in both lungs. Epithelium at sites containing the p53 mutation was morphologically abnormal, exhibiting squamous metaplasia and mild to moderate atypia. No invasive tumor was found in the tracheobronchial tree or any other location. Cells from peripheral blood, kidney, liver, and lymph node exhibited no abnormality in the p53 gene. The widespread presence of a single somatic p53 point mutation in the bronchi of a smoker suggests that a single progenitor bronchial epithelial clone may expand to populate broad areas of the bronchial mucosa-a novel mechanism for field carcinogenesis in the respiratory epithelium that may be of importance in assessing individuals for risk of a second primary tumor as well as in devising effective strategies for chemoprevention of lung cancer.
authors.affiliation: Department of Pathology, University of Colorado Health Sciences Center, University of Colorado Cancer Center, Denver, Colorado 80262, USA. wilbur.franklin@uchsc.edu
authors.forename: W A
authors.initials: WA
authors.lastname: Franklin
authors.forename: A F
authors.initials: AF
authors.lastname: Gazdar
authors.forename: J
authors.initials: J
authors.lastname: Haney
authors.forename: I I
authors.initials: II
authors.lastname: Wistuba
authors.forename: F G
authors.initials: FG
authors.lastname: La Rosa
authors.forename: T
authors.initials: T
authors.lastname: Kennedy
authors.forename: D M
authors.initials: DM
authors.lastname: Ritchey
authors.forename: Y E
authors.initials: YE
authors.lastname: Miller
mesh_terms: D000368:Aged; D001980:Bronchi / Q000473:pathology*; D003062:Codon; D004848:Epithelium / Q000473:pathology; D005091:Exons; D005260:Female; D016158:Genes, p53; D006801:Humans; D008173:Lung Diseases, Obstructive / Q000235:genetics*; D008175:Lung Neoplasms / Q000209:etiology; D008297:Male; D017354:Point Mutation; D012150:Polymorphism, Restriction Fragment Length; D018807:Polymorphism, Single-Stranded Conformational; D012907:Smoking / Q000009:adverse effects*
chemical_list: D003062:Codon