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Immunologic proliferation marker Ki-S2 as prognostic indicator for lymph node-negative breast cancer

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Author

Summary, in English

BACKGROUND: Proper treatment of lymph node-negative breast cancer depends on an accurate prognosis. To improve prognostic models for this disease, we evaluated whether an immunohistochemical marker for proliferating cells, Ki-S2 (a monoclonal antibody that binds to a 100-kd nuclear protein expressed in S, G2, and M phases of the cell cycle), is an accurate indicator of prognosis.

METHODS: We studied 371 Swedish women with lymph node-negative breast cancer; the median follow-up time was 95 months. The fraction of tumor cells in S phase was assessed by flow cytometry, and tumor cell proliferation was measured immunohistochemically with the monoclonal antibodies Ki-S2 and Ki-S5 (directed against the nuclear antigen Ki-67). A combined prognostic index was calculated on the basis of the S-phase fraction, progesterone receptor content, and tumor size.

RESULTS: In multivariate analyses that did or did not (263 and 332 observations, respectively) include the S-phase fraction and the combined prognostic index, the Ki-S2 labeling index (percentage of antibody-stained tumor cell nuclei) emerged as the most statistically significant predictor of overall survival, disease-specific survival, and disease-free survival (all two-sided P<.0001). In the risk group defined by a Ki-S2 labeling index of 10% or less, life expectancy was not statistically significantly different from that of age-matched women without breast cancer, whereas the group with a high Ki-S2 labeling index had an increased risk of mortality of up to 20-fold.

CONCLUSIONS: Cellular proliferation is a major determinant of the biologic behavior of breast cancer. Prognosis is apparently best indicated by the percentage of cells in S through M phases of the cell cycle. Measurement of the Ki-S2 labeling index of a tumor sample may improve a clinician's ability to make an accurate prognosis and to identify patients with a low risk of recurrence who may not need adjuvant therapy.

Publishing year

1999-02-03

Language

English

Pages

8-271

Publication/Series

Journal of the National Cancer Institute

Volume

91

Issue

3

Document type

Journal article

Publisher

Oxford University Press

Topic

  • Cancer and Oncology

Keywords

  • Adult
  • Aged
  • Aged, 80 and over
  • Analysis of Variance
  • Antibodies, Monoclonal
  • Antigens, Neoplasm
  • Biomarkers, Tumor
  • Breast Neoplasms
  • Disease-Free Survival
  • Female
  • Flow Cytometry
  • Humans
  • Immunohistochemistry
  • Ki-67 Antigen
  • Lymphatic Metastasis
  • Middle Aged
  • Predictive Value of Tests
  • Prognosis
  • S Phase
  • Survival Analysis
  • Sweden

Status

Published

ISBN/ISSN/Other

  • ISSN: 1460-2105