Prognostic value of TP53 protein accumulation in human primary breast cancer: an analysis by luminometric immunoassay on 1491 tumor cytosols.
The tumor suppressor gene TP53 is implicated in the regulation of normal cell growth and division, DNA repair and apoptosis. Mutations in this gene usually give rise to a conformationally altered protein which is stably expressed at high levels. We have studied TP53 protein accumulation in routinely prepared cytosols from 1491 human primary breast cancer specimens (median follow-up of patients alive, 66 months), using a quantitative luminometric immunoassay (LIA). The TP53-LIA values varied between 0 and 153.53 (median 0.20 ng/mg protein). Median TP53 levels were significantly higher in ER- and PgR-negative tumors. In Cox univariate regression analysis, when analyzed as a continuous variable, increasing TP53 levels were related with a poor relapse-free survival (p < 0.01). In multivariate analysis for relapse-free survival, including age, menopausal status, tumor size, nodal status and steroid hormone receptor status, TP53 accumulation, when analyzed as a dichotomized variable, was an independent factor for predicting the rate of relapse with a relative relapse rate (95% confidence limits) of 1.39 (1.19-1.63). In conclusion, the LIA for the TP53 protein can easily be performed on cytosols routinely prepared for steroid hormone receptor analysis, it is a quantitative assay, and it may be useful in establishing the relation of TP53 accumulation and breast cancer prognosis.
Berns
E M
EM
Division of Endocrine Oncology (Department of Medical Oncology), Dr. Daniel den Hoed Cancer Center, Rotterdam, The Netherlands. Berns@bidh.azr.nl
De Witte
H H
HH
Klijn
J G
JG
Willman
K
K
Look
M P
MP
Meijer-Van Gelder
M E
ME
Benraad
T J
TJ
Foekens
J A
JA
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000737:chemistry*; D003600:Cytosol / Q000737:chemistry; D005260:Female; D006801:Humans; D007118:Immunoassay; D008875:Middle Aged; D011379:Prognosis; D016159:Tumor Suppressor Protein p53 / Q000032:analysis* / Q000276:immunology
D016159:Tumor Suppressor Protein p53