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 norm al cell growth and division, DNA repair and apoptosis. Mutations in th is gene usually give rise to a conformationally altered protein which is stably expressed at high levels. We have studied TP53 protein accum ulation in routinely prepared cytosols from 1491 human primary breast cancer specimens (median follow-up of patients alive, 66 months), usin g a quantitative luminometric immunoassay (LIA). The TP53-LIA values v aried between 0 and 153.53 (median 0.20 ng/mg protein). Median TP53 le vels were significantly higher in ER-and PgR-negative tumors. In Cox u nivariate 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, includi ng age, menopausal status, tumor size, nodal status and steroid hormon e receptor status, TP53 accumulation when analyzed as a dichotomized v ariable, was an independent factor for predicting the rate of relapse with a relative relapse rate (95% confidence limits) of 1.39 (1.19-1.6 3). In conclusion, the LIA for the TP53 protein can easily be performe d 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.