title: Multicentric breast cancer: clonality and prognostic studies.
abstract: Clonality of multicentric breast cancer has traditionally been difficult to assess. We aimed to assess this using analysis of TP53 status (expression and mutation status). These results were then incorporated into an analysis of prognostic factors in multicentric tumours in a 10-year follow up study. Clonal status of multicentric breast cancer foci (n = 88 foci) was determined by immunohistochemical and molecular studies of TP53 in a total of 40 patients. Prognostic factors from these patients were also compared with 80 age- and stage-matched controls with unicentric breast cancer from the Royal Marsden NHS Foundation Trust Breast Cancer Database. Our results indicate that multicentric breast cancer foci were polyclonal within an individual patient in at least 10 patients (25%) with respect to immunohistochemical staining and in four patients (10%) with respect to abnormal band shifts on single strand conformational polymorphism (SSCP) molecular analysis. No individual variable was predictive of multicentric or unicentric disease. However, there was a worse overall survival in the multicentric breast cancer patients in whom at least two cancer foci stained positively on TP53 immunohistochemistry compared with the matched control group (P = 0.04). In conclusion, these results suggest that a proportion of multicentric breast cancer foci are polyclonal with respect to TP53 status and that TP53 over-expression predicts for a poorer prognosis in multicentric breast cancer.
authors.affiliation: The Institute of Cancer Research, Cotswold Road, Sutton, Surrey SM2 5NG, UK. Rosalind.Eeles@icr.ac.uk
authors.forename: R
authors.initials: R
authors.lastname: Eeles
authors.forename: G
authors.initials: G
authors.lastname: Knee
authors.forename: S
authors.initials: S
authors.lastname: Jhavar
authors.forename: J
authors.initials: J
authors.lastname: Mangion
authors.forename: S
authors.initials: S
authors.lastname: Ebbs
authors.forename: G
authors.initials: G
authors.lastname: Gui
authors.forename: S
authors.initials: S
authors.lastname: Thomas
authors.forename: M
authors.initials: M
authors.lastname: Coppen
authors.forename: R
authors.initials: R
authors.lastname: A'hern
authors.forename: S
authors.initials: S
authors.lastname: Gray
authors.forename: C
authors.initials: C
authors.lastname: Cooper
authors.forename: J
authors.initials: J
authors.lastname: Bartek
authors.forename: J
authors.initials: J
authors.lastname: Yarnold
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology*; D016022:Case-Control Studies; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D011379:Prognosis; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism
chemical_list: C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53