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Mutations, tissue accumulations, and serum levels of p53 in patients with occupational cancers from asbestos and silica exposure
Author(s) -
HusgafvelPursiainen Kirsti,
Kannio Annamaria,
Oksa Panu,
Suitiala Tuula,
Koskinen Heikki,
Partanen Riitta,
Hemminki Kari,
Smith Steven,
RosenstockLeibu Rachel,
BrandtRauf Paul W.
Publication year - 1997
Publication title -
environmental and molecular mutagenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1
H-Index - 87
eISSN - 1098-2280
pISSN - 0893-6692
DOI - 10.1002/(sici)1098-2280(1997)30:2<224::aid-em15>3.0.co;2-f
Subject(s) - immunohistochemistry , biology , mutagen , asbestos , mutant , pathology , exon , microbiology and biotechnology , gene , dna damage , dna , medicine , genetics , immunology , materials science , metallurgy
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 alterations 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 tumors; the agreement between mutational and immunohistochemical analyses was significant (κ˘ = 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 (κ˘ = 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. Environ. Mol. Mutagen. 30:224–230, 1997. © 1997 Wiley‐Liss, Inc.