title: Prognostic significance of p53 overexpression in primary breast cancer; a novel luminometric immunoassay applicable on steroid receptor cytosols.
abstract: A novel quantitative luminometric immunoassay (LIA) has been developed for the measurement of wild-type and mutant p53 protein in extracts from breast tumour tissue. The LIA was found to yield reliable estimates of p53 expression in cytosol samples routinely prepared for steroid receptor analysis as compared with results obtained with immunohistochemical analysis. The LIA was evaluated on 205 primary breast tumour cytosols prepared for steroid receptor analysis and stored frozen at -80 degrees C for 6-8 years, p53 protein being detected in 65% of the samples (range 0.01-23 ng mg-1 protein). Using an arbitrary cut-off value of 0.15 ng mg-1 protein, 30% of the tumours were classified as manifesting p53 overexpression. Significant and independent correlations were found to exist between p53 overexpression and shorter disease-free (P < 0.001) and overall survival (P = 0.039) at a median duration of follow-up of 50 months. p53 overexpression was related to low oestrogen receptor content and high proliferation rate (S-phase fraction). No relationship was found to tumour size or the presence of lymph node metastasis. Three tumours possessed an extremely high p53 content (> 10 ng mg-1 protein), all of which were of medullary or high-grade ductal type, oestrogen and progesterone receptor negative, DNA non-diploid, had S-phase fractions of > 22% and recurred within 1-2 years. In summary, a new sensitive and quantitative LIA suitable for routine analysis of p53 protein in steroid receptor cytosol preparations from breast tumours has been developed to confirm the prognostic importance of p53 protein accumulation in human breast cancer.
authors.affiliation: Department of Oncology, University Hospital, Lund, Sweden.
authors.forename: A
authors.initials: A
authors.lastname: Borg
authors.forename: J
authors.initials: J
authors.lastname: Lennerstrand
authors.forename: M
authors.initials: M
authors.lastname: Stenmark-Askmalm
authors.forename: M
authors.initials: M
authors.lastname: Fernö
authors.forename: A
authors.initials: A
authors.lastname: Brisfors
authors.forename: A
authors.initials: A
authors.lastname: Ohrvik
authors.forename: O
authors.initials: O
authors.lastname: Stål
authors.forename: D
authors.initials: D
authors.lastname: Killander
authors.forename: D
authors.initials: D
authors.lastname: Lane
authors.forename: J
authors.initials: J
authors.lastname: Brundell
mesh_terms: D001943:Breast Neoplasms / Q000737:chemistry* / Q000503:physiopathology / Q000648:ultrastructure; D003600:Cytosol / Q000737:chemistry; D005069:Evaluation Studies as Topic; D005260:Female; D015870:Gene Expression; D016158:Genes, p53; D006801:Humans; D007150:Immunohistochemistry; D008163:Luminescent Measurements; D009154:Mutation; D010641:Phenotype; D011379:Prognosis; D011960:Receptors, Estrogen / Q000032:analysis*; D011980:Receptors, Progesterone / Q000032:analysis*; D012189:Retrospective Studies; D016159:Tumor Suppressor Protein p53 / Q000032:analysis* / Q000096:biosynthesis / Q000235:genetics
chemical_list: D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D016159:Tumor Suppressor Protein p53