title: Mutations, tissue accumulations, and serum levels of p53 in patients with occupational cancers from asbestos and silica exposure.
abstract: In order to determine the relationship between mutations, tissue accumulations, and serum levels of p53 in occupational cancers, we used denaturing gradient gel electrophoresis and DNA sequencing of exons 5-9 of the p53 gene, immunohistochemical analysis for tissue identification of mutant p53 protein, and enzyme-linked immunosorbent assay for serum levels of mutant p53 protein to examine for such alteration in a cohort of individuals with workplace exposure to asbestos or silica, and resultant lung cancers or mesotheliomas. DNA analysis detected mutations in 5 of 18 (28%) tumors, and tissue accumulations of protein were detected in 7 of 20 (35%) tumors; the agreement between mutational and immunohistochemical analyses was significant (kappa = 0.62, P = 0.002). Serum elevations of protein were detected in 4 of 11 (36%) cases with available serum samples; the agreement between tissue alterations and serum elevations was also significant (kappa = 0.71, P = 0.017). In addition, based on the analysis of banked samples, serum results tended to be consistent over time prior to the diagnosis of disease (positive predictive value = 0.67, negative predictive value = 0.83). These results suggest that serum levels of p53 are reasonably accurate in reflecting tissue alterations in p53 at the gene and/ or protein level and may be early biomarkers of disease risk.
authors.affiliation: Finnish Institute of Occupational Health, Helsinki, Finland.
authors.forename: K
authors.initials: K
authors.lastname: Husgafvel-Pursiainen
authors.forename: A
authors.initials: A
authors.lastname: Kannio
authors.forename: P
authors.initials: P
authors.lastname: Oksa
authors.forename: T
authors.initials: T
authors.lastname: Suitiala
authors.forename: H
authors.initials: H
authors.lastname: Koskinen
authors.forename: R
authors.initials: R
authors.lastname: Partanen
authors.forename: K
authors.initials: K
authors.lastname: Hemminki
authors.forename: S
authors.initials: S
authors.lastname: Smith
authors.forename: R
authors.initials: R
authors.lastname: Rosenstock-Leibu
authors.forename: P W
authors.initials: PW
authors.lastname: Brandt-Rauf
mesh_terms: D000328:Adult; D000368:Aged; D001195:Asbestosis / Q000235:genetics*; D001483:Base Sequence; D004586:Electrophoresis / Q000379:methods; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism; D008297:Male; D008654:Mesothelioma / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D009369:Neoplasms / Q000453:epidemiology / Q000235:genetics*; D016273:Occupational Exposure; D012829:Silicosis / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000097:blood* / Q000235:genetics / Q000378:metabolism
chemical_list: D016159:Tumor Suppressor Protein p53