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- Title
Immunologic proliferation marker Ki-S2 as prognostic indicator for lymph node-negative breast cancer.
- Authors
Rudolph, Pierre; Alm, Per; Heidebrecht, Hans-Jurgen; Bolte, Hendrik; Ratjen, Virgo; Baldetorp, Bo; Ferno, Marten; Olsson, Hakan; Parwaresch, Reza; Rudolph, P; Alm, P; Heidebrecht, H J; Bolte, H; Ratjen, V; Baldetorp, B; Fernö, M; Olsson, H; Parwaresch, R
- Abstract
<bold>Background: </bold>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.<bold>Methods: </bold>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.<bold>Results: </bold>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.<bold>Conclusions: </bold>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.
- Subjects
IMMUNOHISTOCHEMISTRY; CELL proliferation; MONOCLONAL antibodies; PROGNOSIS; BREAST cancer
- Publication
JNCI: Journal of the National Cancer Institute, 1999, Vol 91, Issue 3, p271
- ISSN
0027-8874
- Publication type
journal article
- DOI
10.1093/jnci/91.3.271