title: Prognostic value of TP53 protein accumulation in human primary breast cancer: an analysis by luminometric immunoassay on 1491 tumor cytosols.
abstract: 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.
authors.affiliation: Division of Endocrine Oncology (Department of Medical Oncology), Dr. Daniel den Hoed Cancer Center, Rotterdam, The Netherlands. Berns@bidh.azr.nl
authors.forename: E M
authors.initials: EM
authors.lastname: Berns
authors.forename: H H
authors.initials: HH
authors.lastname: De Witte
authors.forename: J G
authors.initials: JG
authors.lastname: Klijn
authors.forename: K
authors.initials: K
authors.lastname: Willman
authors.forename: M P
authors.initials: MP
authors.lastname: Look
authors.forename: M E
authors.initials: ME
authors.lastname: Meijer-Van Gelder
authors.forename: T J
authors.initials: TJ
authors.lastname: Benraad
authors.forename: J A
authors.initials: JA
authors.lastname: Foekens
mesh_terms: 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
chemical_list: D016159:Tumor Suppressor Protein p53