| 1. |
- Bagwell, C B, et al.
(författare)
-
Optimizing flow cytometric DNA ploidy and S-phase fraction as independent prognostic markers for node-negative breast cancer specimens
- 2001
-
Ingår i: Cytometry. - : Wiley. - 0196-4763 .- 1097-0320. ; 46:3, s. 121-135
-
Tidskriftsartikel (refereegranskat)abstract
- Developing a reliable and quantitative assessment of the potential virulence of a malignancy has been a long-standing goal in clinical cytometry. DNA histogram analysis provides valuable information on the cycling activity of a tumor population through S-phase estimates; it also identifies nondiploid populations, a possible indicator of genetic instability and subsequent predisposition to metastasis. Because of conflicting studies in the literature, the clinical relevance of both of these potential prognostic markers has been questioned for the management of breast cancer patients. The purposes of this study are to present a set of 10 adjustments derived from a single large study that optimizes the prognostic strength of both DNA ploidy and S-phase and to test the validity of this approach on two other large multicenter studies. Ten adjustments to both DNA ploidy and S-phase were developed from a single node-negative breast cancer database from Baylor College (n = 961 cases). Seven of the adjustments were used to reclassify histograms into low-risk and high-risk ploidy patterns based on aneuploid fraction and DNA index optimum thresholds resulting in prognostic P values changing from little (P < 0.02) or no significance to P < 0.000005. Other databases from Sweden (n = 210 cases) and France (n = 220 cases) demonstrated similar improvement of DNA ploidy prognostic significance, P < 0.02 to P < 0.0009 and P < 0.12 to P < 0.002, respectively. Three other adjustments were applied to diploid and aneuploid S-phases. These adjustments eliminated a spurious correlation between DNA ploidy and S-phase and enabled them to combine independently into a powerful prognostic model capable of stratifying patients into low, intermediate, and high-risk groups (P < 0.000005). When the Baylor prognostic model was applied to the Sweden and French databases, similar significant patient stratifications were observed (P < 0.0003 and P < 0.00001, respectively). The successful transference of the Baylor prognostic model to other studies suggests that the proposed adjustments may play an important role in standardizing this test and provide valuable prognostic information to those involved in the management of breast cancer patients.
|
|
| 2. |
- Baldetorp, Bo, et al.
(författare)
-
DNA and cell cycle analysis as prognostic indicators in breast tumors revisited
- 2001
-
Ingår i: Clinics in Laboratory Medicine. - 0272-2712 .- 1557-9832. ; 21:4, s. 875-
-
Tidskriftsartikel (refereegranskat)abstract
- Both DNA ploidy and S-phase ploidy are promising prognostic factors for node-negative breast cancer patients. Based largely on the analysis of one large study, much of the reported problems with these factors have been caused by some unappreciated complexities in categorizing DNA ploidy into low- and high-risk groups and the lack of some necessary adjustments to eliminate unwanted correlations between DNA S-phase and ploidy. When both DNA ploidy and S-phase are compensated properly, they become independent prognostic markers, forming a powerful prognostic model.
|
|
| 3. |
- 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.
|
|
| 4. |
- Barkardottir, Rosa B, et al.
(författare)
-
Haplotype analysis in Icelandic and Finnish BRCA2 999del5 breast cancer families
- 2001
-
Ingår i: European Journal of Human Genetics. - : Springer Science and Business Media LLC. - 1476-5438 .- 1018-4813. ; 9:10, s. 773-779
-
Tidskriftsartikel (refereegranskat)abstract
- The 999del5 mutation is the single, strong BRCA2 founder mutation in Iceland and the most common BRCA1/2 founder mutation in Finland. To evaluate the origin and time since spreading of the 999del5 mutation in Iceland and in Finland, we constructed haplotypes with polymorphic markers within and flanking the BRCA2 gene in a set of 18 Icelandic and 10 Finnish 999del5 breast cancer families. All Icelandic families analysed shared a common core haplotype of about 1.7 cM. The common ancestors for the Icelandic families studied were estimated to trace back to 340-1000 years, not excluding the possibility that the mutation was brought to Iceland during the settlement of the country. Analysis of the Finnish families revealed two distinct haplotypes. A rare one, found in three families in the old settlement region in southwestern Finland, shared a four-marker (0.5 cM) core haplotype with the Icelandic 999del5 haplotype. A distinct approximately 6 cM haplotype was shared by seven 999del5 Finnish families estimated to have a common ancestry 140-300 years ago. These families cluster in two geographical regions in Finland, in the very same area as those with the rare haplotype and also in the most eastern, late settlement region of Finland. The results may indicate a common ancient origin for the 999del5 mutation in Iceland and in Finland, but distinct mutational events cannot be ruled out. The surprising finding of the same mutation in two completely different haplotypes in a sparsely populated area in Finland may suggest gene conversion.
|
|
| 5. |
- Boiesen, P, et al.
(författare)
-
Histologic grading in breast cancer--reproducibility between seven pathologic departments. South Sweden Breast Cancer Group
- 2000
-
Ingår i: Acta Oncologica. - : Informa UK Limited. - 1651-226X .- 0284-186X. ; 39:1, s. 41-45
-
Tidskriftsartikel (refereegranskat)abstract
- Histologic grade, including tubular formations, nuclear grade, and mitotic activity, is a well-documented prognostic factor in breast cancer. In comparison with other prognostic parameters, the evaluation of histologic grade is cheap and can be performed, in principle, in all cases of breast cancer. One possible disadvantage is that the evaluation may vary between different pathological departments. The aim of the present work was therefore to study the reproducibility of the histologic grading system by distributing haematoxylin-erythrosin-stained slides from 93 invasive breast cancers to the seven pathology departments within the southern healthcare region of Sweden. The evaluation was performed blindly and without any knowledge of other clinical parameters. In 31% of the cases the same histologic grade was obtained for all departments. The overall mean kappa was 0.54, indicating a moderate reproducibility. Of the three factors included in histologic grade, the agreement was best for tubular formations and poorest for nuclear grade and mitotic activity. The overall moderate reproducibility should be considered when the clinical usefulness of histologic grading is compared with other prognostic instruments.
|
|
| 6. |
|
|
| 7. |
- Borgfeldt, Christer, et al.
(författare)
-
High tumor tissue concentration of urokinase plasminogen activator receptor is associated with good prognosis in patients with ovarian cancer
- 2003
-
Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136. ; 107:4, s. 658-665
-
Tidskriftsartikel (refereegranskat)abstract
- volved in tumor growth and metastasis. We assayed the components of the uPA system in homogenates of 64 primary epithelial ovarian tumors and 5 metastases and evaluated the association of these parameters to prognosis in the 51 malignant cases. The levels of uPA, PAI-2 and the uPA: PAI-I complex increased with progressive loss of histological differentiation (P-trend <0.001, <0.05 and <0.001). The level of PAI-I was higher in poorly than in well/moderately differentiated tumors (p = 0.03). The content of uPAR was lower in benign tumors as compared to borderline malignancies (p = 0.002), invasive primary tumors (p < 0.001), and metastases (p = 0.002). Surprisingly, the level of uPAR was lower in poorly differentiated as compared to both borderline (p = 0.01) and well differentiated malignant tumors (p = 0.005). Also, the level of uPAR was lower in advanced as compared to early stages of the disease (P-trend = 0.002). The median follow-up time for patients was 5.8 years. High tumor tissue levels of uPAR were associated with longer postoperative survival (HR = 0.4, 95% CI = 0.2-0.8, p = 0.01). In contrast, shorter survival was evident in patients with high tumor levels of uPA from 2 years on after operation (HR = 4.6, 95% CI = 1.2-17, p = 0.02). High tPA levels tended to be associated with shorter overall survival after 2 years (HR = 2.9, 95% 95% Cl = 0.9-9.8, p = 0.08). Although high tumor tissue content of uPAR was associated with a less aggressive phenotype characterized by well differentiated histology and longer survival, low content of uPAR in the poorly differentiated tumors and metastases presumably results from increased elimination of uPAR. (C) 2003 Wiley-Liss, Inc.
|
|
| 8. |
- Chebil, G, et al.
(författare)
-
Comparison of immunohistochemical and biochemical assay of steroid receptors in primary breast cancer - Clinical associations and reasons for discrepancies
- 2003
-
Ingår i: Acta Oncologica. - : Informa UK Limited. - 1651-226X .- 0284-186X. ; 42:7, s. 719-725
-
Tidskriftsartikel (refereegranskat)abstract
- Estrogen ( ER) and progesterone receptor (PgR) status was analysed in paraffin-embedded breast cancer material with immunohistochemical (IHC) technique and compared with corresponding analyses in cytosols ( CYT). ER showed the same status (positive/negative) with both methods in 88% of the samples (352/ 402). The concordance was also high for PgR status (81% [321/394]). Besides values near cut-off, heterogeneity in the distribution of receptor positive and negative nuclei within a tumour sample was the main reason for discordances. Histological type, presence of sclerosis, necrosis and non-invasive cells, and technical artefacts seem to be of only limited importance for explaining discordances. All patients have been treated with adjuvant tamoxifen for two years. The two subgroups, which were ERCYT+/ ERIHC+ or ERCYT-/ERIHC+, both had a significantly better progression-free survival (PFS; median follow-up: almost 6 years) than the ERCYT -/ERIHC- group (p< 0.001 and p = 0.007, respectively). The remaining group, ERCYT+/ERIHC-, had an intermediate PFS. For PgR, the associations with PFS were weaker, with significantly better PFS than the PgR(CYT)-/PgR(IHC)- group being found only for the PgR(CYT)+/PgR(IHC) - group (p = 0.03).
|
|
| 9. |
|
|
| 10. |
|
|
