Immunologic proliferation marker Ki-S2 as prognostic indicator for lymph node-negative breast cancer
(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.
(Less)
- author
- Rudolph, P ; Alm, P LU ; Heidebrecht, H J ; Bolte, H ; Ratjen, V ; Baldetorp, B LU ; Fernö, M LU ; Olsson, H LU and Parwaresch, R
- organization
- publishing date
- 1999-02-03
- type
- 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<.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}}, }