| 1. |
- Kuhling, H, et al.
(författare)
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Expression of cyclins E, A, and B, and prognosis in lymph node-negative breast cancer
- 2003
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Ingår i: Journal of Pathology. - : Wiley. - 0022-3417. ; 199:4, s. 424-431
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Tidskriftsartikel (refereegranskat)abstract
- Unexpected outcomes in breast cancer demand a refinement of prognostic criteria. This study therefore investigated the prognostic relevance of cyclin expression in a cohort of 332 T1-T2 NO infiltrating ductal carcinomas with long-term follow-up (median 99 months). By univariate analysis, tumour size, histopathological grade, hormone receptor content, cyclin E, cyclin B, and the Ki-S5 (Ki-67) index significantly predicted disease-specific and metastasis-free survival. Cyclin A did not achieve statistical significance. In a multivariate analysis, both cyclin E [relative risk (RR) 2.01, p = 0.021] and cyclin B (RR 1.85, p = 0.033) were selected as independent prognosticators of metastasis-free survival when the Ki-67 index was omitted, but (only cyclin E expression was associated with disease-specific survival (RR 2.56, p = 0.006). When Ki-67 was included as a covariate, cyclin E lost its significance with respect to disease-specific survival but remained significant for metastasis-free survival. In an analogous analysis including Ki-67, the number of concurrently overexpressed cyclins did not attain statistical significance regarding disease-specific survival but was selected as the leading predictor of metastatic disease. It is concluded that combined overexpression of cyclins may imply genetic instability enhancing metastatic potential, but that survival ultimately depends on the proliferative activity of tumour cells. Copyright (C) 2003 John Wiley Sons, Ltd.
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| 2. |
- Rudolph, P, et al.
(författare)
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Correlation between p53, c-erbB-2, and topoisomerase II alpha expression, DNA ploidy, hormonal receptor status and proliferation in 356 node-negative breast carcinomas : prognostic implications
- 1999
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Ingår i: Journal of Pathology. - 0022-3417. ; 187:2, s. 16-207
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Tidskriftsartikel (refereegranskat)abstract
- Various new prognostic indicators have been identified for mammary carcinomas, but the issue of their significance remains unsettled. The prognostic impact of p53, c-erbB-2, and topoisomerase II alpha expression was investigated in relation to standard prognostic factors for carcinomas of the breast and to the tumour cell growth fraction. Paraffin-embedded specimens of 356 node-negative infiltrating ductal carcinomas were stained immunohistochemically using a polyclonal antiserum to c-erbB-2, and the monoclonal antibodies DO-1 (p53), Ki-S4 (topoisomerase II alpha), and Ki-S5 (Ki-67). The patients were followed for a median duration of 99 months. Both p53 and c-erbB-2 were significantly associated with high tumour grade, large tumour size, DNA aneuploidy, lack of steroid hormone receptors, young age, and increased topoisomerase II alpha and Ki-67 expression levels. The correlation of p53 and c-erbB-2 was not significant. Topoisomerase II alpha and Ki-67 scores closely paralleled each other, indicating that both reflect the proliferative activity of tumour cells. A univariate analysis of overall (OS), specific (SS), and disease-free survival (DFS) revealed all the above-mentioned parameters to be statistically significant except patient age, which was relevant only to overall survival. Multivariate analysis with inclusion of all covariates selected tumour size and proliferation (topoisomerase II alpha and Ki-67) indices as independent predictors of survival in all three models. No additional information was gained by p53 or c-erbB-2. It is concluded that the proliferative activity, as assessed by topoisomerase II alpha or Ki-67 immunostaining, is the most useful indicator of breast cancer prognosis, except for tumour size.
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| 3. |
- Rudolph, P, et al.
(författare)
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Differential prognostic impact of the cyclins E and B in premenopausal and postmenopausal women with lymph node-negative breast cancer
- 2003
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136. ; 105:5, s. 674-680
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Tidskriftsartikel (refereegranskat)abstract
- Searching for new prognostic factors, we investigated the influence of cyclin expression on breast cancer prognosis. A total of 273 archival tumor specimens from patients with pT1/pT2 NO breast cancers treated by surgery and local irradiation were immunostained for cyclins E, A and B. Outcome was evaluated as metastasis-free (MFS) and diseasespecific survival (DSS) over a median observation period of 99 months. In postmenopausal women, DSS was significantly predicted by cyclin E, and in premenopausal patients by cyclin B. No statistical significance was found for cyclin A. When the prognostic impact of cyclins was compared to that of standard prognostic indicators in a multivariate analysis, both cyclin E and cyclin B were selected as independent predictors of survival in postmenopausal and premenopausal patients, respectively. After inclusion of Ki-67 in the model, cyclin E lost its significance, whereas cyclin B remained the only independent prognostic factor with a hazard ratio of 4.5 (p = 0.026) for tumor-related death. Assessment of cyclin expression may, therefore, refine current prognostic models if considered in relation to menopausal status. The prognostic relevance of cyclins is likely attributable to an influence on proliferation, cell survival and genetic instability. Awareness of the molecular mechanisms leading to deregulated cyclin expression may guide decisions for risk-adapted therapy regimens.
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| 4. |
- Rudolph, P, et al.
(författare)
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Immunologic proliferation marker Ki-S2 as prognostic indicator for lymph node-negative breast cancer
- 1999
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 1460-2105 .- 0027-8874. ; 91:3, s. 8-271
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Tidskriftsartikel (refereegranskat)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 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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