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B Baldetorp

Publications and source records attributed to B Baldetorp.

At least 73 records · Page 4Linked to original sources

Prognostic potential of flow cytometric S-phase and ploidy prospectively determined in primary breast carcinomas.

In a prospective study of a consecutive breast cancer series accumulated in the period 1978-82, the S-phase fraction (SPF) and ploidy status were determined by flow cytometry performed on cell nuclei derived from samples of 580 primary tumors. Sixty percent of the tumors were non-diploid. After correction for debris the median SPF values were 7.3% overall, 12% for non-diploid tumors, and 2.9% for diploid tumors (2.6% when nodal subsets N2 and N3 and cases with metastases at presentation were excluded). The SPF values correlated both to tumor size (p = 0.008) and to the number of positive axillary lymph nodes (p = 0.03). At clinical follow-up in 1986, 467 unilateral breast cancer patients who had undergone radical treatment for cure could be evaluated with respect to the prognostic value of both the SPF value and ploidy status. The median duration of follow-up was then 59 months (range 2-90), and the median time-to-recurrence 24 months (range 2-69, n = 137). At follow-up in 1991, 201/467 of the patients had died, the median duration of follow-up being 50 months (range 2-126) for the decreased, and 119 (range 6-148) for the survivors. In multivariate analysis (Cox's proportional hazards models), the strongest independent predictors of distant recurrence-free survival (DRFS) were the number of positive axillary lymph nodes (p less than 0.0001), the debris-corrected SPF value alone (p = 0.003, versus p = 0.05 for uncorrected value), and ploidy status combined with the corrected SPF value (p = 0.0002). When age was taken into account, both the corrected SPF value and the ploidy-SPF combination were predictors of crude survival (p = 0.006 and p = 0.002, respectively). In univariate life-table analysis, the 5-year DRFS rate was 93% in node-negative (N0) cases with an SPF less than 7.3%, as compared to 80% in those with an SPF greater than or equal to 7.3% (p = 0.005). Among node-positive cases, the prognostic value of the SPF was confined to those with 1-3 positive nodes, the 5-year DRFS rate being 68% in cases with an SPF less than 7.3%, as compared to 40% in cases with an SPF greater than or equal to 7.3% (p = 0.01).(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

Prognostic significance of flow cytometric DNA analysis and estrogen receptor content in breast carcinomas--a 10 year survival study.

The prospective prognostic significance of flow cytometry derived DNA-ploidy status, the level of the S-phase fraction (SPF), estrogen receptor (ER) content, and combinations of these factors, was evaluated with respect to overall survival (OS) in a series of 516 breast cancer patients who were without signs of residual or distant disease after primary completed treatment. The median duration of survival follow-up time was ten years (range, 95-148 months) for surviving patients. Of the single factors, ER was the only significant predictor among node-negative patients; the ten-year OS rate was 71% in cases with ER-rich tumors vs. 62% for ER-poor tumors (p = 0.03). Where tumors were both non-diploid and ER-poor, the ten-year OS rate was 58%, as compared to 75% for the remaining node-negative patients (p = 0.003), who constituted a low-risk group whose survival was comparable with that in the age-matched normal population. Among patients with 1-3 positive nodes, the ten-year OS rate was 65% in patients whose tumors had an SPF < 7.3% vs. 50% if the SPF was > or = 7.3% (p = 0.01), and 58% in cases with ER-rich tumors vs. 45% where the tumors were ER-poor (p = 0.02). In a multivariate analysis, apart from age and menopausal status the combination of ploidy status and ER content was the significant (p = 0.002) predictor of OS in node-negative patients. Thus, combining ploidy and ER status, both of which are variables easily determined, enabled the selection of a subgroup of patients at high risk of relapse and reduced survival whose prognosis should be improved by effective adjuvant systemic treatment, whereas the remaining low risk N0 patients can not be expected to derive any survival benefit from adjuvant therapy since their predicted survival is already on a par with that of the general population.

Adult↗

Flow cytometry DNA analysis and prediction of loco-regional recurrences after mastectomy in breast cancer.

The study concerns whether DNA flow cytometry and estrogen receptor analysis might help predict which breast cancer patients, particularly node-positive ones, were at the greatest risk of developing loco-regional recurrence (LRR). Such patients would best benefit from postoperative radiotherapy following modified radical mastectomy and axillary lymph node dissection. After this type of surgery, 506 patients were followed up for a median time of nearly 5 years. Among the 235 patients given postoperative radiotherapy, the loco-regional control rate was 100% in N0 cases (n = 93), 94% in cases with 1-3 positive nodes (n = 90), 93% in cases with 4-9 positive nodes (n = 43), and 67% in cases with 10 or more positive nodes (n = 9). Among the 271 non-irradiated patients, the corresponding figures for loco-regional control were 91% in N0 cases (n = 141), 71% in cases with 1-3 positive nodes (n = 84), 65% in cases with 4-9 positive nodes (n = 31), and 67% in cases with 10 or more positive nodes (n = 15). Ploidy status, level of S-phase fraction, estrogen receptor content, and primary tumor size did not, in the present material, yield significant additional information with regard to the risk of LRR in the different nodal subgroups, a finding confirmed in multivariate analysis where the only significant predictor of LRR was the number of positive nodes (p = 0.01). Adjuvant tamoxifen treatment could not replace postoperative radiotherapy for achieving loco-regional tumor control, the overall rate of which was 81% among patients treated with tamoxifen only (n = 117), as compared with 98% among those also treated with radiotherapy (n = 54) (p = 0.003).

Breast Neoplasms↗

Flow cytometric DNA index and S-phase fraction in breast cancer in relation to other prognostic variables and to clinical outcome.

One frequently used classification of flow cytometric DNA ploidy status (diploid versus nondiploid) was compared with a division into seven ploidy classes based on DNA index (DI) and number of cell populations (hypodiploid, diploid, near-hyperdiploid, hyperdiploid, tetraploid, hypertetraploid, and multiploid). The latter ploidy classification showed a better correlation with prognosis and other prognostic factors (i.e., lymph node involvement, estrogen and progesterone receptor status, and S-phase fraction). The improvement in correlation was mainly due to the identification of near-hyperdiploid cases (DI 1.00-1.14) which could be combined with the diploid cases to form a group with favourable prognosis. In contrast to cases with a small increase in DNA content (near-hyperdiploid), those with a small decrease of DNA content (hypodiploid) manifested a more aggressive disease. In multivariate analysis, S-phase fraction (SPF) was a more important prognostic factor than both the improved or the conventional ploidy classification.

Adolescent↗

Proliferation and DNA ploidy in malignant breast tumors in relation to early oral contraceptive use and early abortions.

In 175 premenopausal breast cancer patients, a history of oral contraceptive (OC) use before 20 years of age was significantly associated with higher tumor cell proliferative activity, as indicated by a higher S-phase fraction (SPF), and a higher fraction of DNA aneuploid tumors, compared with later or never users (P = 0.05 and p = 0.01, respectively). The higher SPF among early OC users was apparent in patients with aneuploid tumors but not in patients with euploid tumors. Abortions (spontaneous or induced) before the first full-term pregnancy also were associated with a higher SPF compared with other young patients with breast cancer (P = 0.03). Adjusting for parity and abortions or OC use, respectively, an early OC use was associated with a 43% higher SPF and early abortions were associated with 49% higher SPF. Younger patients had a higher SPF and a higher frequency of aneuploid tumors, but this was found to be because the users of OC had a lower median age at diagnosis. Among never users, no significant age relationship was seen for SPF or the frequency of aneuploidy. For the DNA analyses there is a selection of patients with breast cancer with larger tumors, and therefore the conclusions drawn in this article may not be generalizable to patients with smaller primary tumors, e.g., cases diagnosed at breast cancer screening. The higher tumor proliferative activity and frequency of aneuploidy in early OC users are in line with previously reported findings of worse prognostic indicators and a worse survival in early users of OC compared with other young women with breast cancer.

Abortion, Induced↗

Analysis of peripheral blood lymphocyte phenotype and function during dexamethazone treatment of progressive multiple sclerosis.

Five patients with chronic progressive multiple sclerosis (MS) and three control patients with lumbar disc herniation were treated with dexamethazone during 14 days. The effect on peripheral blood T-cell subsets and on the proliferative response of peripheral blood mononuclear cells (PBMC) to pokeweed mitogen (PWM) and anti-mu antibody was analyzed. Before treatment, the proportion of CD3+ and CD4+ PBMC was similar in MS and control patients, but the proportion of CD8+ and DR+ PBMC was lower and the PBMC were less responsive to anti-mu stimulation in MS patients compared to controls. Steroid treatment induced reversible granulocytosis and lymphocytosis. CD3+ and CD4+ cells increased and DR+ cells decreased in MS patients but not in controls. Proliferation of anti-mu stimulated PBMC increased in MS-patients during the two weeks of treatment, but decreased in controls. The enhancement in the MS patients of pre-existing immune abnormalities suggests that a cautious attitude is warranted in the use of steroid treatment in chronic progressive MS.

Adult↗

ERBB2 amplification in breast cancer with a high rate of proliferation.

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.

Adult↗

Flow cytometric DNA content in Kaposi's sarcoma by histologic stage. Comparison with angiosarcoma.

Kaposi's sarcoma occurs as a multicentric proliferation of endothelial cells. A lesion may progress through several histologic stages, culminating in a lesion consisting of spindle cells with marked nuclear atypia that may be indistinguishable from angiosarcoma. To assess the relationship between the nuclear DNA content and the stage, 29 paraffin-embedded biopsy specimens from 25 cases of Kaposi's sarcoma were classified according to their histologic stage and flow cytometric DNA ploidy status. The findings were compared with those in 14 angiosarcomas (5 postmastectomy angiosarcomas, 6 other cutaneous angiosarcomas and 3 angiosarcomas of deep tissues). The Kaposi's sarcoma specimens studied included samples with irregular lymphatic-like channels (stage 1), transition to spindle cells (stage 1t2), nodular spindle-cell aggregates (stage 2), scattered atypical spindle cells (stage 2t3) and histologic features indistinguishable from those of angiosarcoma (stage 3). Of the 25 Kaposi's sarcoma specimens of stage 2 or less, 17 had a diploid DNA distribution while an additional 8 had broad diploid G0G1 peaks (peridiploid, with a coefficient of variation greater than 7.5%, present in similar proportions in stages 1, 1t2 and 2). One of three stage 2t3 lesions showed tetraploidy while the single stage 3 specimen (from the leg) was aneuploid, with a DNA index (DI = 1.16) similar to that of four of the five postmastectomy angiosarcomas (DI = 1.14 to 1.20). An additional three angiosarcomas also showed nondiploid distributions (DI = 1.16, 1.98 and 2.13, respectively); the remainder were diploid or peridiploid. These results support previous cytogenetic data suggesting a normal karyotype in Kaposi's sarcoma up to stage 2, with atypia beginning as cells acquire numerical and structural chromosomal aberrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Indicators of prognosis in node-negative breast cancer.

Measures of the proliferative activity of tumor cells have prognostic value in patients with node-negative breast cancer. We studied 367 women in southern Sweden who had undergone surgical resection for such cancer. Tumor specimens were analyzed with DNA flow cytometry in order to estimate both the DNA content (ploidy) and the fraction of cells in the synthetic phase of the cell cycle (S phase). The median duration of follow-up was four years; 28 percent of the patients received adjuvant therapy, usually with tamoxifen (n = 83). A multivariate analysis based on complete data on 250 patients included the following covariates: age (greater than or equal to 75, 50 to 74, and less than or equal to 49 years), tumor size (less than or equal to 20 vs. greater than 20 mm), concentration of estrogen and progesterone receptors (less than 10 vs. greater than or equal to 10 fmol per milligram of protein), ploidy (diploid vs. nondiploid), and S-phase category (fraction of cells in S phase: less than 7.0 percent, 7.0 to 11.9 percent, and greater than or equal to 12 percent). The S-phase fraction yielded the most prognostic information, followed by progesterone-receptor status and tumor size. A prognostic model based on these three variables identified 37 percent of the patients as constituting a high-risk group with a fourfold increased risk of distant recurrence. In the remaining 63 percent of the patients, the five-year overall survival rate (92 +/- 4 [+/- SE] percent) did not differ from the expected age-adjusted rate for Swedish women. We conclude that a prognostic index that includes indicators of the proliferative activity of tumor cells may be able to identify women with node-negative breast cancer in whom the risk of recurrence is sufficiently low that adjuvant chemotherapy can be avoided.

Age Factors↗

Complex karyotypic changes, including rearrangements of 12q13 and 14q24, in two leiomyosarcomas.

Cytogenetic investigation of short-term cultures from two leiomyosarcomas revealed complex karyotypic changes in both cases. The first tumor, a subcutaneous leiomyosarcoma of the knee, had the karyotype 70-80,XY, +X, +Y, +1, +1, +2, +2, +3, +3, +4, +4, +7, +7, +8, +8, +9, +10, +15, +15, +16, +16, +18, +19, +20, +21, +21, +22, +22,t(?;5)(5;21)(?;q35p11;q11), t(?;5)(5;21)(?;q35p11;q11), +del(11)(q22),der(13)t(12;13)(q13;q22),der(14)t(9;14)(p11;p11), +14p+, +t(20;?)(q13;?), +t(20;?)(q13;?), +2 mar. A polyploidized clone with 120-150 chromosomes was also observed. DNA flow cytometry revealed only one abnormal peak, corresponding to a DNA index of 1.76. The other tumor, a uterine leiomyosarcoma, had the karyotype 61-67, X, -X, +1, +3, +5, +6, +7, +8, +9, +12, +13, +15, +t(1;1)(p32;q32), +der(1)t(1;8)(p13;q11), +del(2)(p11), +del(2)(q22), +del(2)(q22), +del(3)(p13), +i(5p),t(8;14)(q24;q24), +der(8)t(8;14) (q24;q24), +del(10)(p12),der(11)t(11;15)(p15;q11),t(16;?)(p13;?),t(16;?)(q24;?), der dic(17) (17pter----cen----17q25::hsr::17q25----cen----17pte r), +t(19;?)(p13;?), +der dic(20)(20pter----cen----20q12::hsr::20q12----cen----+ ++20pter), +mar. The DNA index was 1.59. The finding in these leiomyosarcomas of rearrangements of the same regions of chromosomes 12 and 14 that are involved in the tumor-specific t(12;14)(q14-15;q23-24) of uterine leiomyoma indicates that the same genes in 12q and 14q might be important in the pathogenesis of benign and malignant smooth muscle tumors.

Aged↗

Flow cytometry in primary breast cancer: improving the prognostic value of the fraction of cells in the S-phase by optimal categorisation of cut-off levels.

The use of continuous prognostic variables is clinically impractical, and arbitrarily chosen cut-off points can result in a loss of prognostic information. Here we report findings from a study of primary breast cancer, showing how the prognostic value of the fraction of cells in the S-phase of the cell cycle (SPF), as measured by flow cytometry, can be affected by the SPF cut-off level(s) adopted. It was possible to evaluate the SPF in 566 (94%) of 603 consecutive cases where fresh frozen specimens were available in a tumour bank at our department. Clinically, all patients were without distant spread at the time of diagnosis, and the median duration of follow-up was 4 years. Using different survival end-points and chi 2 values for each cut-off level, two optimal cut-off points, at the 7% and 12% levels, were consistently obtained for the SPF. Furthermore, both disease-free survival and the relative risk of recurrence exhibited a non-linear relationship with SPF values; the curves implied that the prognosis was better among patients with SPF values about 2-5% than in patients with lower SPF values (parabolic shape), though the relationship with higher SPF values approached linearity. The non-linearity of the curves is incompatible with the general use of the median SPF as a prognostic cut-off value. An alternative procedure might be to use two cut-off levels, one to distinguish patients with the lowest SPF values (i.e. within the parabolic survival curve) from those with higher values (i.e. with a survival curve approaching linearity), the other to distinguish between patients with intermediate SPF values and those with high values (i.e. within the almost linear part of the survival curve). The 7% and 12% obtained here would be suitable for this purpose. We conclude that prognostic information can be gained by dividing the SPF into three prognostic categories (less than 7.0%, 7.0-11.9% and greater than or equal to 12%), instead of using the median SPF level.

Adult↗

Cellular DNA content and prognosis of high-grade soft tissue sarcoma: the Scandinavian Sarcoma Group experience.

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.

Adolescent↗

Flow cytometric DNA ploidy analysis of soft tissue sarcomas. A comparative study of preoperative fine needle aspirates and postoperative fresh tissues and archival material.

Flow cytometric (FCM) DNA ploidy measurements on frozen fresh samples of soft tissue sarcomas were compared with the corresponding analyses on preoperative fine needle aspirates and postoperative formalin-fixed archival tissues from the same tumors. A concordance in ploidy status (diploid versus non-diploid) was obtained for 63% of the fresh tissue-fine needle aspiration (FNA) sample comparisons and for 85% of the fresh tissue-archival material comparisons. The majority of discordances in the fresh tissue-FNA sample comparisons could be explained by FNA sampling errors. In the remaining discordant cases (3 of 27 FNA sample comparisons and 6 of 40 archival material comparisons), sampling errors could not explain the differences in ploidy status. The discordant cases were evenly distributed among the different sampling methods. Method reproducibility was not responsible for the differences in ploidy determinations; tumor heterogeneity may be an explanation for the discrepancies. This study showed that archival soft tissue sarcoma samples are as well suited for DNA ploidy analysis as are fresh frozen tissues.

Archives↗

Statistical evaluation of cell kinetic data from DNA flow cytometry (FCM) by the EM algorithm.

Flow cytometric DNA measurements yield the amount of DNA for each of a large number of cells. A DNA histogram normally consists of a mixture of one or more constellations of G0/G1-, S-, G2/M-phase cells, together with internal standards, debris, background noise, and one or more populations of clumped cells. We have modelled typical DNA histograms as a mixed distribution with Gaussian densities for the G0/G1 and G2/M phases, an S-phase density, assumed to be uniform between the G0/G1 and G2/M peaks, observed with a Gaussian error, and with Gaussian densities for standards of chicken and trout red blood cells. The debris is modelled as a truncated exponential distribution, and we also have included a uniform background noise distribution over the whole observation interval. We have explored a new approach for maximum-likelihood analyses of complex DNA histograms by the application of the EM algorithm. This algorithm was used for four observed DNA histograms of varying complexity. Our results show that the algorithm works very well, and it converges to reasonable values for all parameters. In simulations from the estimated models, we have investigated bias, variance, and correlations of the estimates.

Algorithms↗

Complex karyotypic anomalies in a bizarre leiomyoma of the uterus.

Cytogenetic investigation of short-term cultures from a bizarre leiomyoma of the uterus, a tumor type not hitherto karyotypically characterized, revealed two abnormal clones with multiple complex rearrangements. Three-fourths of the aberrant cells were hypodiploid with the composite karyotype 38-44,XX,-6,-7,-10, -11,+20,-22,r(1),der(2)(:2p23----cen----2q13::1q21---- 1qter),der(2)t(2; 9)(p21;q13),t(5;?)(q35;?), t(5;?),(q35;?),+der(5)t(5;15)(q11;q15), der(8)t(8;11)(q24;q13),t(15;?)(p12;?),der(16)t(12;16)(q13;p13),+r,+mar. The remaining abnormal mitoses were hypotetraploid, with chromosome numbers ranging from 74 to 86. These massively rearranged cells showed the same markers that were found in the hypodiploid clone, but in duplicate, indicating that this clone had arisen through polyploidization of hypodiploid cells. Flow cytometry revealed a DNA index of 1.03.

Female↗

Flow cytometry DNA ploidy and number of cell populations in the primary breast cancer and their correlation to the prognosis.

In a prospective study on 516 breast cancer patients flow cytometry DNA ploidy and number of cell populations (defined as number of DNA stem lines) detected in the primary tumor were evaluated for prognostic purposes. The median follow-up time was about 5 years. In the 241 node negative cases, those patients with three or more cell populations had the worst prognosis, with a distant recurrence-free survival rate of about 60% at five years compared to 90% in cases with only one cell population detected in the primary tumor. The number of tumor involved axillary lymph nodes was the outstanding prognostic indicator which was confirmed in 275 node positive patients; DNA ploidy and number of cell populations did not give any significant prognostic information in this group of patients.

Antineoplastic Agents↗

A sensitive method to introduce membrane-bound proteins into recipient cells based on affinity enrichment of lipid vesicles to the recipient cell prior to fusion.

A sensitive analytical procedure for studying membrane-bound structures has been developed. Membrane glycoproteins inserted into liposomes were transferred to recipient cells by use of a lectin, concanavalin A, bound to the cells as a bridge to generate proximity between the recipient cell and the glycoprotein-containing liposome, prior to exposure to the fusing agent, poly(ethylene glycol). Partially purified histocompatibility antigen from rats was introduced into the membrane of human lymphocytes. After treating the cells with poly(ethylene glycol) under fusion conditions, some of the antigen present in the preparation could not be eluted with alpha-methyl mannoside and EDTA, indicating that incorporation in the cell membrane had taken place. This antigen remained exposed on the lymphocyte surface for approximately 1 h as demonstrated by sensitivity of the lymphocytes to the lytic effect of an antiserum to the histocompatibility antigen in the presence of complement. Some of the lectin molecules seemed to be internalized in the cells but no induction of cell mitosis was observed. The described method gives an opportunity to work with small amounts of membrane proteins inserted into liposomes, introducing them into recipient cells for analysis of their biological activities.

Animals↗

Cell cycle phase-dependent induction of ornithine decarboxylase-antizyme.

The activities of ornithine decarboxylase (ODC) and ODC inhibitory protein (ODC-antizyme) were studied in Ehrlich ascites tumor cells, separated according to their position in the cell cycle by centrifugal elutriation. Release and/or synthesis of ODC-antizyme was induced by putrescine treatment. Each mouse received an intraperitoneal injection of 25 mumoles of putrescine at 0, 1, 2, and 3 hr after tumor transplantation. Tumor cells obtained from putrescine-treated and control mice at 4 hr after transplantation were separated into fractions representing all phases of the cell cycle. The cell cycle distribution of the tumor cells in each fraction was determined by flow cytometry. In control tumor cells the ODC activity exhibited two maxima; in late-G1/early-S and in late-S/G2. A marked decrease in ODC activity was observed in mid-S phase. This decrease coincided with maximum ODC-antizyme activity (revealed by putrescine treatment), suggesting that ODC-antizyme is involved in the regulation of ODC activity during the cell cycle.

Animals↗