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

Rudolph, P ; Alm, P LU ; Heidebrecht, H J ; Bolte, H ; Ratjen, V ; Baldetorp, B LU ; Fernö, M LU ; Olsson, H LU orcid and Parwaresch, R (1999) In Journal of the National Cancer Institute 91(3). p.8-271
Abstract

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... (More)

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.

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organization
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Contribution to journal
publication status
published
subject
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
in
Journal of the National Cancer Institute
volume
91
issue
3
pages
8 pages
publisher
Oxford University Press
external identifiers
  • pmid:10037106
  • scopus:0033518604
  • pmid:10037106
ISSN
1460-2105
DOI
10.1093/jnci/91.3.271
language
English
LU publication?
yes
additional info
The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Pathology, (Lund) (013030000), Oncology, MV (013035000)
id
c5fb32b3-3921-4076-9219-292a084dcb57 (old id 1114357)
date added to LUP
2016-04-01 16:39:09
date last changed
2022-01-28 21:12:12
@article{c5fb32b3-3921-4076-9219-292a084dcb57,
  abstract     = {{<p>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.</p><p>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.</p><p>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&lt;.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.</p><p>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.</p>}},
  author       = {{Rudolph, P and Alm, P and Heidebrecht, H J and Bolte, H and Ratjen, V and Baldetorp, B and Fernö, M and Olsson, H and Parwaresch, R}},
  issn         = {{1460-2105}},
  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}},
  language     = {{eng}},
  month        = {{02}},
  number       = {{3}},
  pages        = {{8--271}},
  publisher    = {{Oxford University Press}},
  series       = {{Journal of the National Cancer Institute}},
  title        = {{Immunologic proliferation marker Ki-S2 as prognostic indicator for lymph node-negative breast cancer}},
  url          = {{http://dx.doi.org/10.1093/jnci/91.3.271}},
  doi          = {{10.1093/jnci/91.3.271}},
  volume       = {{91}},
  year         = {{1999}},
}