Testing of functional integrity of p53 protein in primary breast cancer by a rapid quantitative p53-p21 double assay may improve the clinical value of p53.
We hypothesized that inclusion of p21(WAF1), an indicator of biological function, into the p53 assay might improve the clinical value of p53 in breast cancer diagnosis. In primary breast carcinomas (n = 146) and healthy/benign controls (n = 40), the p53 protein was quantified by luminescence immunoassay. The p21 protein was simultaneously measured by quantitative ELISA in a representative subgroup of breast cancers (n = 52) and controls (n = 17). In controls, p53 but not p21 was detectable. In almost all cancer tissues, p53 and p21 expression could be quantified. There was no correlation between the concentrations of both proteins. However, if p53 exceeded a threshold of 1.0 ng/mg protein, p21 expression was significantly reduced compared with samples with p53 below threshold. p21 was normally distributed in the low-p53 subpopulation, but not in the high-p53 group. The histologic parameter 'grade III' was more often found (p = 0.002) in tumors with p53 >1.0 ng/mg protein than in those with p53 below the threshold. Histological criteria of high tumor malignancy were found more often in cases with high p53 but low p21. Consequently, in clinical routine, a quantitative double assay of p53 and p21(WAF1) might help to discriminate breast cancers with preserved or impaired/lost p53 function.
Westhof
Gregor
G
Department of Obstetrics and Gynecology, University of Witten/Herdecke School of Medicine, Witten, Germany. gregor@westhof.com
Olbrecht
Michael
M
Wolff
Manfred
M
Schiermeier
Sven
S
Zimmermann
Ralf C
RC
Hatzmann
Wolfgang
W
D014408:Biomarkers, Tumor / Q000032:analysis; D001940:Breast / Q000737:chemistry; D001943:Breast Neoplasms / Q000175:diagnosis*; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000032:analysis*; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods*; D005260:Female; D006801:Humans; D049449:Luminescence; D051736:Proto-Oncogene Proteins c-mdm2 / Q000032:analysis; D016159:Tumor Suppressor Protein p53 / Q000032:analysis* / Q000235:genetics
D014408:Biomarkers, Tumor; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016159:Tumor Suppressor Protein p53; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2