| 1. |
- 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.
|
|
| 2. |
- Fernö, Mårten, et al.
(författare)
-
Preoperative fine needle aspiration from human breast cancer is a valuable sampling material for progesterone receptor and cytometric DNA analysis
- 1996
-
Ingår i: Acta Oncologica. - : Informa UK Limited. - 1651-226X .- 0284-186X. ; 35:S8, s. 19-25
-
Tidskriftsartikel (refereegranskat)abstract
- In a breast cancer series (n = 54), preoperative fine needle aspiration (FNA) was compared with biopsy at primary surgery as a source of material for the determination of progesterone receptor (PgR) content by enzyme immuno assay. The respective results manifested a strong correlation (r(s) = 0.82). The fact that PgR content was usually higher in FNA samples than in the corresponding biopsy samples and the finding that 11% of the tumours were PgR positive in FNA but PgR negative in the corresponding biopsy samples suggest a greater proportion of malignant cells to be obtained with FNA than in surgical biopsy. In another breast cancer series (n = 50), corresponding comparisons for DNA flow cytometry showed concordance in ploidy status (diploid vs. non-diploid) in 84% of cases and a strong correlation in S-phase fraction values (r(s) = 0.70). At DNA image cytometry, concordant results (Auer I + II vs. Auer III + IV) were obtained in 87% of the cases. To sum up, FNA seems to be a useful sampling technique for PgR determination and DNA cytometry.
|
|
| 3. |
- Fernö, Mårten, et al.
(författare)
-
Recurrence-free survival in breast cancer improved by adjuvant tamoxifen--especially for progesterone receptor positive tumors with a high proliferation
- 1995
-
Ingår i: Breast Cancer Research and Treatment. - 1573-7217. ; 36:1, s. 23-34
-
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.
|
|
| 4. |
- Fernö, Mårten, et al.
(författare)
-
Urokinase plasminogen activator, a strong independent prognostic factor in breast cancer, analysed in steroid receptor cytosols with a luminometric immunoassay
- 1996
-
Ingår i: European Journal of Cancer. - : Elsevier BV. - 1879-0852 .- 0959-8049. ; 32a:5, s. 793-801
-
Tidskriftsartikel (refereegranskat)abstract
- Urokinase plasminogen activator (uPA) is involved in the activation of different proteases which participate in the degradation of extracellular matrix, thereby enhancing the invasive capacity of tumour cells. uPA has been shown to be of prognostic importance in breast cancer. We have analysed uPA with a new luminometric immunoassay (LIA), applicable in cytosol samples routinely used for oestrogen-receptor (ER) and progesterone-receptor (PgR) analyses. At a cut-off value of 0.62 ng uPA/mg protein, 33% (230/688) samples were classified as representing high uPA tumours. High uPA content was found to be associated with shorter recurrence-free survival (median observation time: 42 months), ER and PgR negativity, increased p53 expression, DNA non-diploidy and a high S-phase fraction (SPF), but not with lymph node involvement or tumour size (< or = 20 mm versus > 20 mm). In the subgroup of patients not treated with systemic adjuvant therapy, multivariate analysis showed uPA to be an independent prognostic factor together with lymph node status and SPF. If these results can be reproduced, uPA may be a factor suitable for inclusion in a prognostic index.
|
|
| 5. |
- Gudmundsson, Thorkell E., et al.
(författare)
-
Methodological aspects of flow cytometry DNA analysis in endometrial carcinoma, with special reference to sampling and reproducibility
- 1996
-
Ingår i: Acta Oncologica. - : Informa UK Limited. - 1651-226X .- 0284-186X. ; 35:8, s. 999-1006
-
Tidskriftsartikel (refereegranskat)abstract
- Two adjacent paraffin-embedded sections manifested concordance in ploidy status in 96% of cases (45/47), and the standard deviation (SD) for SPF was 2.7%. Analysis of 'micro-heterogeneity', within a distance of < or = 700 microm, yielded results for concordant ploidy status in 94% of cases, and the SD for SPF was 1.9% (n = 17). Frozen and paraffin-embedded material yielded concordant results for ploidy status in 87% (39/45) of cases, and SPF values were significantly lower (mean difference 1.5%) in the frozen samples. Diagnostic and repeat curettage material yielded concordant results for DNA ploidy status in 85% (40/47) of cases, and no significant difference in mean SPF (12% vs. 11%) was found. Discordant DNA ploidy results were attributable to small differences in the DNA histograms influencing the interpretation of near-diploid, near-tetraploid and small non-diploid cell populations, and the influence of debris on SPF estimation. On the basis of our findings and the practical advantage we recommend paraffin-embedded material from diagnostic curettage for FCM DNA analysis; the results are available sooner and the handling and transportation of tumor samples is more convenient.
|
|
| 6. |
- Gudmundsson, Thorkell E, et al.
(författare)
-
The prognostic information of DNA ploidy and S-phase fraction may vary with histologic grade in endometrial carcinoma
- 1995
-
Ingår i: Acta Oncologica. - : Informa UK Limited. - 1651-226X .- 0284-186X. ; 34:6, s. 803-812
-
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.
|
|
| 7. |
- Gustafson, Pelle, et al.
(författare)
-
Flow cytometric S-phase fraction in soft-tissue sarcoma: prognostic importance analysed in 160 patients
- 1997
-
Ingår i: British Journal of Cancer. - 1532-1827. ; 75:1, s. 94-100
-
Tidskriftsartikel (refereegranskat)abstract
- We could determine the S-phase fraction (SPF) by flow cytometric DNA analysis of paraffin archival material in 160 of 260 patients with soft-tissue sarcoma of extremity and trunk wall. The prognostic value of SPF was compared with other clinicopathological factors. The median follow-up time was 16 (6-31) years. In a univariate analysis, deep tumour location, increasing tumour size and histological malignancy grade, microscopic tumour necrosis, vascular invasion, DNA non-diploidy and high SPF (>3.0%) were associated with poor metastasis-free survival. In a multivariate analysis, microscopic tumour necrosis and high SPF were independently prognostic for metastasis. Used in combination with tumour size, microscopic tumour necrosis and vascular invasion, SPF could identify a group of patients with a 5-year metastasis-free survival rate of 0.97. This group constituted one-quarter of all patients. Patients with low SPF who did recur had a prolonged clinical course both as regards metastases and local recurrence. We conclude that SPF is a valuable adjunct in prognostication in soft-tissue sarcoma.
|
|
| 8. |
- Kjellén, Elisabeth, et al.
(författare)
-
A Phase I/II Evaluation of Metoclopramide as a Radiosensitiser in Patients with Inoperable Squamous Cell Carcinoma of the Lung
- 1995
-
Ingår i: European Journal of Cancer. - : Elsevier BV. - 1879-0852 .- 0959-8049. ; 31:13-14, s. 2196-2202
-
Tidskriftsartikel (refereegranskat)abstract
- The feasibility of administering metoclopramide (MCA) as a radiosensitizer has been evaluated in 23 patients with a pathological or cytological diagnosis of a squamous cell carcinoma of the lung, clinically evaluated as inoperable. All patients received 40-60 Gy radiotherapy fractionated into 1.8 Gy fractions 5 times per week (Monday-Friday). Two MCA treatment regimens were used: (i) MCA at 2 mg/kg administered by intravenous infusion 1-2 h prior to radiotherapy 3 times per week (Monday, Wednesday, Friday); and (ii) MCA at 1 mg/kg administered by intravenous infusion 1-2 h prior to radiotherapy 5 times per week (Monday-Friday). 11 of the 23 patients treated with radiotherapy and MCA had none to mild pneumonitis or fibrosis and another 8 of the 23 had moderate levels. No patient had their therapy interrupted due to radiation-related side-effects. The MCA-related side-effects were as expected, i.e. 78% of the patients experienced sedation/tiredness and 48% expressed restlessness/anxiety symptoms. Both the total dose and serum levels of MCA were significantly associated to the MCA side-effect profile. Tumour response, duration of tumour response and survival were significantly positively correlated to the total and weekly doses of MCA administered to the patients during their radiotherapy treatment. These favourable phase II data have justified the initiation of a phase II/III randomised multicentred trial being carried out in Europe to evaluate MCA as a radiosensitiser.
|
|
| 9. |
- Koul, Anjila, et al.
(författare)
-
Identification of TP53 gene mutations in uterine corpus cancer with short follow-up
- 1997
-
Ingår i: Gynecologic Oncology. - : Elsevier BV. - 1095-6859 .- 0090-8258. ; 67:3, s. 295-302
-
Tidskriftsartikel (refereegranskat)abstract
- The involvement of the TP53 tumor suppressor gene in uterine corpus cancer was investigated by single-stranded conformation polymorphism and sequence analysis of its exons 4 to 10. Mutations were found in 12 (18.5%) of 65 cases. Ten of these 12 were single-base substitutions (8 missense and 2 nonsense mutations), whereas 2 were frame-shifting mutations. TP53 gene mutations correlated significantly with advanced surgical stage of disease (P = 0.006) and unfavorable tumor histology types (P = 0.003), whereas the association to myometrial wall invasion did not reach statistical significance (P = 0.054). TP53 gene mutations also correlated significantly with allelic loss at TP53 locus (P = 0.024), absence of estrogen (P = 0.045) and progesterone receptors (P = 0.001), DNA nondiploidy (P = 0.002), and high S-phase fraction values (P = 0.002). Our results suggest that inactivation of the TP53 checkpoint function is associated with disease transition into a stage of rapid progression and spread.
|
|
| 10. |
- Persson, Karin, et al.
(författare)
-
Chromosomal aberrations in breast cancer: a comparison between cytogenetics and comparative genomic hybridization
- 1999
-
Ingår i: Genes, Chromosomes and Cancer. - 1045-2257. ; 25:2, s. 115-122
-
Tidskriftsartikel (refereegranskat)abstract
- The analysis of chromosomal imbalances in solid tumors using comparative genetic hybridization (CGH) has gained much attention. A survey of the literature suggests that CGH is more sensitive in detecting copy number aberrations than is karyotyping, although careful comparisons between CGH and cytogenetics have not been performed. Here, we compared cytogenetics and CGH in 29 invasive breast cancers after converting the karyotypes into net copy number gains and losses. We found 15 tumors (56%) with a significant agreement between the two methods and 12 tumors (44%) where the methods were in disagreement (two cases failed CGH analysis). Interestingly, in 13 of the 15 tumors where the two methods were concordant, there was also a strong correlation between chromosome index and DNA index by flow cytometry. In the opposite situation, i.e., when chromosome and DNA indices were not matching, there was disagreement between cytogenetics and CGH in 10 of the 12 tumors. Of the discordant cases, all except one had a "simple" abnormal karyotype. Unresolved chromosomal aberrations (marker chromosomes, homogeneously staining regions, double minutes) could not completely explain the differences between CGH and karyotyping. A likely explanation for the discrepancies is that the methods analyzed different cell populations. Gains and losses found by CGH represented the predominant (often aneuploid) clone, whereas the abnormal, near-diploid karyotypes represented minor cell clone(s), which, for unknown reasons, had a growth advantage in vitro.
|
|
