Microsatellite gene instability and abnormality of mismatch gene proteins in human lung cancer from chromate-exposed workers

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Our previous study for human lung cancer from chromate-exposure workers have revealed that chromate exposure induce the particular mutation pattern in the p53 gene of human lung cancer (Biochem Biophys Res Com 139, 95-100, 1997). In this study, we examined the genomic instability in 40 Lung cancers from 33 chromate-exposure workers and 29 lung cancers patients without chromate exposure (control samples) using 6 microsatellite markers. Thirty (75.0%) of the 40 tumors with chromate exposure showed RER+. On the other hand, only 4 (13.3%) of the 29 tumors without chromate exposure showed the replication error-positive phenotype (RER+). The frequency of RER+ in tumors with chromate exposure was higher than that in tumors without chromate exposure (p<0.0001). Moreover, the duration of chromate exposure but not Brinkman index may be associated with numbers of MSI positive.To clarify the relationship between RER+ and the abnormality of mismatch repair gene, we examined the expressions of hMLH1 and hMSH2 protein in 28 chromate lung cancers and 28 non-chromate lung cancers by immunohistochemistry. All 28 non-chromate lung cancers strongly expressed both hMLH1 and hMSH proteins. On the other hand, 14 (50%) of 28 chromate lung cancers moderately or weakly expressed hMLH protein. Eight (29%) of 28 chromate lung cancers moderately or weakly expressed hMSH protein. It is possible that RER+ in chromate lung cancer may be due to the abnormality of mismatch repair genes.