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Träfflista för sökning "WFRF:(Fernö Mårten) ;pers:(Baldetorp Bo)"

Sökning: WFRF:(Fernö Mårten) > Baldetorp Bo

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1.
  • Alvegård, Thor, et al. (författare)
  • Cellular DNA content and prognosis of high-grade soft tissue sarcoma: the Scandinavian Sarcoma Group experience
  • 1990
  • Ingår i: Journal of Clinical Oncology. - 1527-7755. ; 8:3, s. 538-547
  • Tidskriftsartikel (refereegranskat)abstract
    • The nuclear DNA content of 148 high-grade soft tissue sarcomas of the extremities and trunk was determined by flow cytometry, using tumor material from paraffin-embedded tissue. The patients were part of a prospective randomized clinical trial on the efficacy of adjuvant single-agent chemotherapy with doxorubicin. Chemotherapy did not improve the metastasis-free survival (MFS). After a median follow-up time of 48 months (range, 2 to 97), a multivariate analysis of prognostic factors for developing metastatic disease was performed. DNA aneuploidy was found to be an independent prognostic risk factor in addition to histologic malignancy grade IV, intratumoral vascular invasion, tumor size over 10 cm, and male sex. Patients with none or one risk factor had a 5-year MFS of 79%, with two risk factors 65%, with three risk factors 43%, and with four and five risk factors 0%. About one half (78 of 148) of the patients with three factors or less belonged to a group with a MFS over 60%. The combination of different risk factors, including DNA aneuploidy, seems to be a useful prognostic model for soft tissue sarcomas, which could be of value to select high-risk patients for further trials with adjunctive therapy.
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2.
  • Baldetorp, Bo, et al. (författare)
  • Different calculation methods for flow cytometric S-phase fraction: prognostic implications in breast cancer? The Swedish Society of Cancer Study Group
  • 1998
  • Ingår i: Cytometry. - 0196-4763. ; 33:4, s. 385-393
  • Tidskriftsartikel (refereegranskat)abstract
    • S-phase fraction (SPF), estimated in the flow cytometric DNA histogram, is a prognostic factor in breast cancer. There are, however, some inherent difficulties in the estimation of SPF, such as the influence of debris, aggregates, and normal cells. Most of the available SPF calculation principles try to consider these difficulties, but so far no consensus has been reached with regard to which principle is to be recommended. The aim of the present study was to investigate the prognostic impact of SPF when estimated with different calculation methods in frozen breast cancer samples from 350 patients. Two nonparametric (Rman, Rmin/both rectangle) and three parametric (ACAS/DNA-base, ModFit, and MultiCycle) calculation methods, with and without correction for debris and aggregates, were used. The mean values for SPF varied from 4.3% (ACAS/DNA-base with correction for debris and aggregates) to 9.4% (MultiCycle without any correction for background). The pairwise correlation between methods varied considerably (R = 0.72-0.98). After categorization of SPF values into low SPF (lower two tertiles) and high SPF (upper tertile), all methods yielded statistically significant Pvalues for recurrence-free survival (median follow-up time 67 months), both univariately (0.0004-< 0.0001) and multivariately (0.048-0.0004), after adjusting for nodal status, tumor size, and estrogen receptor status. SPF with background correction did not yield lower P values than SPF without. Regardless of which method was used, SPF showed similar correlations with lymph node involvement, tumor size, and estrogen receptor content. In conclusion, as the mean value of SPF for different calculation methods varies, each laboratory must be restricted to use only one method. Background correction does not seem to improve the prognostic impact of SPF in DNA histograms. Based on the experiences obtained in the present study, S-phase calculation methods without background correction may therefore be the most suitable for routine evaluation of DNA histograms of fresh frozen breast cancer material (ModFit, MultiCycle, and Rman [the latter only for experienced operators]). The nonparametric Rmin, with an automatic setting of the region used for SPF calculation, may be an alternative, but suffers from the disadvantage of not being commercially available yet.
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3.
  • Baldetorp, Bo, et al. (författare)
  • Image cytometric DNA analysis in human breast cancer analysis may add prognostic information in diploid cases with low S-phase fraction by flow cytometry
  • 1992
  • Ingår i: Cytometry. - : Wiley. - 0196-4763 .- 1097-0320. ; 13:6, s. 577-585
  • Tidskriftsartikel (refereegranskat)abstract
    • Measurements of DNA ploidy can be performed either with image cytometry (ICM) or flow cytometry (FCM); both methods provide independent prognostic information in primary breast cancer. The aim of the present investigation was to compare the two methods and to relate the findings to prognosis (median follow-up 42 months). Concordance in ploidy status (diploid, tetraploid, aneuploid) was obtained in 76% of the samples (168/222). When the fraction of S-phase cells (SPF) from FCM analysis was also taken into consideration, four different groups of samples were obtained (Flow I-IV), which were considered to correspond to the Auer classification (Auer I-IV) of DNA histograms obtained from image cytometry. Complete concordance between the two techniques now was 70% (155/222). Samples classified as Flow I (diploid or near-diploid with low SPF) and Auer I had a distant metastasis rate of 3/60 (5%), as compared to 62/154 (40%) for all other combinations of the Flow and Auer classifications taken together. Thus, the only findings of prognostic importance were that some samples were Flow I but not Auer I, or vice versa. These two groups represent 17 (7.7%) and 14 (6.3%), respectively, of the total number of samples, and had frequencies of distant metastasis similar to those of the other high-risk groups, namely, 7/17 and 5/14, respectively. In a multivariate analysis, flow cytometric S-phase value was a stronger prognostic factor than either the Flow and Auer classification. We conclude that when routine FCM DNA analysis is used, diploid or near-diploid samples with a low S-phase value should be reanalyzed with ICM.
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4.
  • Baldetorp, Bo, et al. (författare)
  • Improved DNA flow cytometric, DNA ploidy, and S-phase reproducibility between 15 laboratories in analysis of breast cancer using generalized guidelines
  • 2003
  • Ingår i: Cytometry. - : Wiley. - 0196-4763 .- 1097-0320. ; 56A:1, s. 1-7
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundLack of generalized guidelines for DNA flow cytometric analysis (FCM) may be the main reason for its limited use in the clinical management of breast cancer.MethodsAfter an initial interlaboratory reproducibility study (Round I), we concluded that it was the evaluation of the DNA histograms rather than the technical performance of the analysis that was the main reason for discordant results between laboratories. Guidelines for the interpretation of DNA histograms were therefore drawn up. We present here data from a new reproducibility study (Round II) using these guidelines.ResultsFor 10 laboratories also participating in Round I, use of the guidelines increased the concordance in DNA ploidy status from 89% to 100% for the 46 samples used in both rounds. The concordance rate for SPF also increased; mean rs-value increased from 0.81 to 0.88, and mean kappa value (lower two-thirds versus upper third versus not reported) increased from 0.55 to 0.71. Five new laboratories, participating only in Round II, also agreed with the 10 original laboratories regarding DNA ploidy status. With the inclusion of all 15 laboratories, we obtained a mean rs-value of 0.81 and a mean kappa value of 0.72 for SPF.ConclusionsGeneralized guidelines for DNA FCM increase interlaboratory agreement, which is highly important in clinical routines and in multicenter studies. Furthermore, inexperienced FCM laboratories using generalized guidelines can produce and interpret DNA FCM data equally as well as experienced laboratories.
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5.
  • Baldetorp, Bo, et al. (författare)
  • Proliferative index obtained by DNA image cytometry. Does it add prognostic information in Auer IV breast cancer?
  • 1998
  • Ingår i: Analytical and Quantitative Cytology and Histology. - 0884-6812. ; 20:2, s. 144-152
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: To investigate whether the S + G2/M fraction (proliferative index) is a prognostic determinant in breast cancers classified as Auer IV. STUDY DESIGN: Prognostic evaluation of Auer IV DNA histograms with respect to the high versus low S + G2/M fraction, obtained by image cytometry on consecutive breast cancer imprint preparations. RESULTS: When studying recurrence-free survival (n = 136), the prognostic value of S + G2/M was found to vary with time: it was negligible before the median time to relapse (1.5 years) but thereafter statistically significant, in both univariate and multivariate analysis. The same pattern was found when overall survival was used as the end point; the effect was delayed to about the median time until death (three years). Tumors with a low S + G2/M fraction were smaller and more often estrogen receptor- and progesterone receptor-positive than those with a high S + G2/M fraction. CONCLUSION: According to ICM-DNA values corresponding to the S + G2/M region, patients with breast cancers classified as Auer IV can be divided into subgroups with different tumor characteristics and prognoses.
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6.
  • Baldetorp, Bo, et al. (författare)
  • Reproducibility in DNA flow cytometric analysis of breast cancer: comparison of 12 laboratories' results for 67 sample homogenates
  • 1995
  • Ingår i: Cytometry. - : Wiley. - 0196-4763 .- 1097-0320. ; 22:2, s. 115-127
  • 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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7.
  • Bergqvist, A, et al. (författare)
  • Uterus and endometrium: Flow cytometric DNA analysis in endometriotic tissue compared to normal uterine endometrium
  • 1996
  • Ingår i: Human Reproduction. - : Oxford University Press (OUP). - 0268-1161 .- 1460-2350. ; 11:8, s. 1731-1735
  • Tidskriftsartikel (refereegranskat)abstract
    • Endometriotic tissue sometimes shows an invasive pattern. but the growth regulation of the tissue is insufficiently characterized. In a research programme on factors regulating endometriotic growth, the DNA ploidy status and S-phase fraction (SPF) were studied. Fresh-frozen endometriotic tissue from 14 women and endometrium from 11 of them were studied using flow cytometry. A clear diploid pattern was seen in most cases of endometriotic (8/14) and endometrial (8/11) samples. In the remaining cases the G0/G1 peak was broad and skewed, which might indicate a near-diploid cell population. To clarify this, a second group was studied, consisting of 29 formalin-fixed endometriotic samples from 22 women and endometrium from five of them. All these samples were diploid, with one having a broad G0/G1 peak. No convincing difference in SPF between endometrium and endometriotic tissue was found, as the calculations had to be handled with caution because of debris in many samples. Although the study of fresh-frozen samples gave some indications of differences in DNA ploidy status, flow of cytometric DNA analysis of formalin fixed samples of endometriosis showed a diploid DNA pattern in all samples. In conclusion, DNA flow cytometry did not show a convincing aneuploid DNA pattern in endometriotic tissue.
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8.
  • Borg, Åke, et al. (författare)
  • c-myc amplification is an independent prognostic factor in postmenopausal breast cancer
  • 1992
  • Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 51:5, s. 687-691
  • Tidskriftsartikel (refereegranskat)abstract
    • The c-myc proto-oncogene was analyzed in 311 cases of primary breast cancer, in 8% of which it was found to be amplified, usually at moderately increased copy number (2-5 copies). The adjacent pvt gene was co-amplified with c-myc in all tumors analyzed. C-myc amplification was significantly correlated to a high S-phase fraction and to amplification of the c-erbB-2 proto-oncogene. Weak relationships were found between c-myc amplification and the presence of lymph-node metastasis, advanced stage, DNA non-diploidy and premenopausal status, but not tumor size, estrogen receptor or progesterone receptor status, or int-2 amplification. C-myc amplification, and especially a high gene copy number (greater than 5 copies), was significantly related to early recurrence and death in breast cancer, a relationship seen in both the lymph-node-negative and node-positive subcategories. A particularly strong correlation with poor clinical outcome was seen in postmenopausal patients (p greater than 0.0005), an association which persisted in multivariate survival analysis. We conclude that the activation of c-myc is indeed associated with rapidly growing and progressive breast cancer. Gene amplification, on the other hand, is relatively infrequent and occurs mostly at low copy number, implying that tumors are heterogeneous with respect to cell clones harboring c-myc amplification. An immunohistochemical assessment would more accurately illustrate the importance of c-myc activation in human breast cancer. However, the obvious instability of the c-myc transcript and translate suggests that c-myc is not a suitable prognostic marker for routine purposes.
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9.
  • Borg, Åke, et al. (författare)
  • ERBB2 amplification in breast cancer with a high rate of proliferation
  • 1991
  • Ingår i: Oncogene. - 1476-5594. ; 6:1, s. 137-143
  • Tidskriftsartikel (refereegranskat)abstract
    • The ERBB2 proto-oncogene was studied in 539 invasive primary breast tumors and was found amplified (2- greater than 30 copies) in 19%. Amplification was correlated to most known risk factors, including; large tumor size, lymph node positivity and many tumor involved nodes, advanced stage, low patient age (less than 40 years), non-diploidy and hypertetraploidy, and most significantly (P less than 0.00001) to the absence of steroid receptors and to a high rate of proliferation (flow cytometric determined S phase fraction). ERBB2 amplification was strongly associated (P less than 0.0001) with early recurrence and death in breast cancer among node-positive patients. This connection did not, however, remain in multivariate analyses. No correlations to clinical outcome were seen among node-negative patients. Similarly, non-diploid, but not diploid, amplified tumors were particularly aggressive. Furthermore, ERBB2 amplification was associated with a high rate of proliferation and poor prognosis in steroid receptor positive, but not receptor negative tumors. In progesterone receptor positive breast cancer, amplification was an independent and with node status equally powerful (P less than 0.0001) predictor of poor survival. It is concluded that ERBB2 activity is related to an increased tumor growth rate but not directly to metastasizing ability. Its clinical relevance as a prognostic factor may be in selecting a high risk subgroup of breast cancer, in general considered as being of good prognosis.
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10.
  • Borg, Åke, et al. (författare)
  • ERBB2 amplification is associated with tamoxifen resistance in steroid-receptor positive breast cancer
  • 1994
  • Ingår i: Cancer Letters. - : Elsevier BV. - 1872-7980 .- 0304-3835. ; 81:2, s. 137-144
  • Tidskriftsartikel (refereegranskat)abstract
    • Amplification and overexpression of the ERBB2 (HER-2/neu) oncogene has been implicated as contributing to the development of human breast cancer, and as a predictor of poor survival. In the present non-randomized study of 871 primary invasive breast tumours, ERBB2 activation was significantly correlated to a shorter disease-free and overall survival in the subgroup of patients receiving adjuvant tamoxifen therapy, but not in the untreated group. Further subcategorization demonstrated the relationship to poor prognosis to be confined to lymph node positive and steroid receptor-positive tumours. We suggest that steroid receptor and ERBB2-positive breast tumours are resistant to tamoxifen therapy and, supported by experimental evidence showing an oestrogen receptor dependent up-regulation of ERBB2 expression upon tamoxifen administration, possibly even growth stimulated by the drug.
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