Comparison between p53 protein measurements using the luminometric immunoassay and immunohistochemistry with detection of p53 gene mutations using cDNA sequencing in human breast tumors.
1998 (English)In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 79, no 4, 376-383 p.Article in journal (Refereed) Published
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 comparedwith those obtained with immunohistochemistry (IHC) on microwave-treated paraffin sections and the p53specific luminometric immunoassay (LIA) on cytosols, all from the same individuals. Thirty-sevenmutations were found using cDNA sequencing and were categorized into A) missense mutations in theevolutionarily 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 defected all 16. In category B, 10 of 13 and 7 of 13mutations were detected, respectively. Some of the samples in category A had a very high p53 proteincontent 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 Iof 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 p53mutations 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.
Place, publisher, year, edition, pages
1998. Vol. 79, no 4, 376-383 p.
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-57016DOI: 10.1002/(SICI)1097-0215(19980821)79:4<376::AID-IJC12>3.0.CO;2-3ISI: 000075117600012OAI: oai:DiVA.org:uu-57016DiVA: diva2:84925