| 1. |
- Baldetorp, Bo, et al.
(författare)
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Reproducibility in DNA flow cytometric analysis of breast cancer: comparison of 12 laboratories' results for 67 sample homogenates
- 1995
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Ingår i: Cytometry. - : Wiley. - 0196-4763 .- 1097-0320. ; 22:2, s. 115-127
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Tidskriftsartikel (refereegranskat)abstract
- Flow cytometric (FCM) DNA analysis yields information on ploidy status and the S-phase fraction (SPF), variables of prognostic importance in breast cancer. The clinical value of the SPF is currently being evaluated in prospective randomized trials. The widespread use of FCM DNA analysis emphasizes the importance of reproducibility (both intra- and interlaboratory). In this study, 67 nuclear suspensions of breast cancer samples were analyzed by 12 laboratories routinely performing FCM DNA analysis in breast cancer. No general guidelines were imposed; each laboratory used its own standard protocols. For DNA ploidy status (diploid vs. non-diploid), agreement was complete for 79% (53/67) of the samples, compared with 64% (43/67) of samples when tetraploidy was considered [i.e., euploid (diploid+tetraploid) vs. aneuploid (the remaining non-diploid)]. For the SPF, pairwise comparison of the results of all 12 laboratories yielded a mean Spearman's rank correlation of 0.78 (range: 0.54-0.93). For those 39 samples being categorized in low or high SPF by all laboratories, all agreed in 14 samples (36%). Similar patterns were obtained with kappa measures, agreement being good for ploidy status (diploid vs. non-diploid; overall kappa = 0.87 and 0.74 for euploid vs. aneuploid), but moderate for the SPF [overall kappa = 0.47 (for low SPF vs. high SPF vs. "no SPF reported")]. Discrepancies were chiefly attributable to differences in the categorization of the S-phase values, rather than in FCM procedures, other critical differences being in the detection and interpretation of near-diploid and small non-diploid cell populations, the definition of tetraploidy, and the choice and execution of the method used for S-phase estimation. Based on the observations of this study, detailed guidelines for FCM analysis and interpretation of data are proposed in the Appendix. Some issues remain, however, e.g., to standardize a method for S-phase calculation and tetraploid definition.
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| 2. |
- Fernö, Mårten, et al.
(författare)
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Recurrence-free survival in breast cancer improved by adjuvant tamoxifen--especially for progesterone receptor positive tumors with a high proliferation
- 1995
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Ingår i: Breast Cancer Research and Treatment. - 1573-7217. ; 36:1, s. 23-34
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Tidskriftsartikel (refereegranskat)abstract
- Although the beneficial effect on breast cancer of adjuvant tamoxifen (TAM) is well established, in the series studied by our group this effect seems to have been restricted to patients with steroid receptor (especially progesterone receptor (PgR)) positive tumors. However, as some patients with PgR-positive tumors manifested recurrence despite adjuvant TAM treatment, the question arose whether some other biological factor(s) could be used to identify these non-responding cases. The level of the S-phase fraction (SPF), as measured by flow cytometry, has been shown to be a useful prognostic marker, prognosis being better in cases where the SPF is low than in those where it is high. The aim of the present study was to relate the prognosis after adjuvant TAM to SPF among patients with PgR-positive tumors. In the PgR-positive group as a whole, the effect of TAM on prognosis was more pronounced in the high SPF group than in the low SPF group (p = 0.005) the respective decrease in 3 year recurrence rate was from 19 to 43% and from 17 to 9%. Multivariate analysis of the data for the TAM-treated group showed the level of PgR concentration (low positive vs. high positive), lymph node status, and tumor size to be independent predictive factors, but not the level of SPF (i.e. high vs. low). By contrast, among patients not treated with TAM, the SPF was a strong independent prognostic factor. To sum up, SPF was a strong independent predictor of outcome only for patients receiving no systemic adjuvant therapy, but not in patients receiving adjuvant TAM. Patients with PgR-positive and high S-phase tumors derived more benefit from TAM than patients with PgR-positive and low SPF tumors.
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| 3. |
- Gudmundsson, Thorkell E, et al.
(författare)
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The prognostic information of DNA ploidy and S-phase fraction may vary with histologic grade in endometrial carcinoma
- 1995
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Ingår i: Acta Oncologica. - : Informa UK Limited. - 1651-226X .- 0284-186X. ; 34:6, s. 803-812
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Tidskriftsartikel (refereegranskat)abstract
- DNA ploidy and S-phase fraction (SPF) were determined by flow cytometry on paraffin-embedded tumor material from 243 patients treated during 1980-1985. Patients with well differentiated and moderately differentiated tumors without solid areas (n = 351) formed a low-risk group (corrected 5-year survival 90%). Twenty-four patients, dead of disease within 5 years, were compared with 52 survivors. The estimated death risk was higher for those with SPF > or = 8.0% compared with those with SPF < 8.0% (odds ratio = 18.2; p < 0.001). SPF was the only independent prognostic factor in a multivariate analysis also including age, clinical stage and grade of differentiation. Patients with moderately differentiated tumors with solid areas or poorly differentiated tumors (n = 208) were regarded as a high-risk group. There was a difference in survival according to ploidy; the corrected 5-year survival was 75% for 106 patients with diploid tumors compared with 44% for those with non-diploid tumors (p < 0.0001). In a multivariate analysis DNA ploidy, age and clinical stage were independent prognostic factors, whereas SPF was no longer significant. Thus, DNA ploidy and SPF have different prognostic values depending on histological grade of endometrial carcinoma.
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