| pubmed-article:9699530 | pubmed:abstractText | The p53 mutational status of 226 representative primary breast cancer samples, derived from a population-based cohort, was analyzed using cDNA-based sequencing. The results were compared with those obtained with immunohistochemistry (IHC) on microwave-treated paraffin sections and the p53 specific luminometric immunoassay (LIA) on cytosols, all from the same individuals. Thirty-seven mutations were found using cDNA sequencing and were categorized into A) missense mutations in the evolutionarily conserved regions; B) missense mutations outside the evolutionarily regions; and C) deletions, insertions and nonsense mutations. Using optimal cut-off values, LIA detected 15 of 16 missense mutations in category A, in which IHC detected all 16. In category B, 10 of 13 and 7 of 13 mutations were detected, respectively. Some of the samples in category A had a very high p53 protein content when measured with the LIA, the reason for this being discussed. IHC detected 0 of 5 stop codon and 0 of 3 deletions/insertions mutations, while the LIA method detected 2 of 5 stop codon mutations and 1 of 3 deletion/insertion mutations. Compared with cDNA sequencing, protein analyses using optimal cut-off values resulted in an overall sensitivity and specificity of 64.9% and 89.9%, respectively, for the LIA method. Corresponding values were 72.2% and 92% for IHC. In addition, patients from whom p53 mutations could be detected by cDNA sequencing had a statistically significant (p = 0.0137) shorter survival, which was not readily apparent using the alternative LIA or IHC approaches at optimal cut-off values. | lld:pubmed |
