title: Prognostic impact of proliferation-associated factors MIB1 (Ki-67) and S-phase in node-negative breast cancer.
abstract: MIB1 proliferation rate (MIB1-PR) and total S-phase fraction (SPF) were retrospectively determined in formalin-fixed, paraffin-embedded sections of 90 primary node-negative breast carcinomas. None of the patients had received adjuvant systemic therapy. Median follow-up in patients still alive at the time of analysis was 37.5 months (16-72 months). Immunostaining of Ki-67 antigen was performed using the monoclonal antibody MIB1 and the APAAP technique. An adjacent 50-microm paraffin section was used for flow cytometric S-phase determination. Results were compared to established clinicopathological prognostic factors. MIB1-PR was significantly correlated to grading (P = 0.018); SPF was significantly correlated with tumour size (P = 0.041) and inversely with steroid hormone receptor status (P = 0.03). A significant correlation between MIB1-PR and SPF was found in aneuploid (P = 0.025) but not in diploid tumours (P = 0.164). In univariate analysis, both MIB1-PR (optimized cut-off of 25%) and SPF (optimized cut-off of 8%) were significant prognostic factors for disease-free survival (DFS) (MIB1-PR, P = 0.0224; SPF, P = 0.0028). In multivariate analysis, however, only SPF remained significant; it was the strongest prognostic factor for DFS (P = 0.0073), stronger than MIB1-PR or established clinicopathological prognostic factors. We thus conclude that MIB1-PR and SPF provide additional prognostic information in node-negative breast cancer. However, in our study, flow cytometrically determined SPF had the greater prognostic impact.
authors.affiliation: Institut für Allgemeine Pathologie und Pathologische Anatomie, Munich,Germany.
authors.forename: P
authors.initials: P
authors.lastname: Dettmar
authors.forename: N
authors.initials: N
authors.lastname: Harbeck
authors.forename: C
authors.initials: C
authors.lastname: Thomssen
authors.forename: L
authors.initials: L
authors.lastname: Pache
authors.forename: P
authors.initials: P
authors.lastname: Ziffer
authors.forename: K
authors.initials: K
authors.lastname: Fizi
authors.forename: F
authors.initials: F
authors.lastname: Jänicke
authors.forename: W
authors.initials: W
authors.lastname: Nathrath
authors.forename: M
authors.initials: M
authors.lastname: Schmitt
authors.forename: H
authors.initials: H
authors.lastname: Graeff
authors.forename: H
authors.initials: H
authors.lastname: Höfler
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000737:chemistry* / Q000473:pathology*; D005260:Female; D005434:Flow Cytometry; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000032:analysis*; D008198:Lymph Nodes / Q000473:pathology; D008875:Middle Aged; D011003:Ploidies; D011379:Prognosis; D012189:Retrospective Studies; D016196:S Phase / Q000502:physiology*
chemical_list: D019394:Ki-67 Antigen