| 1. |
- Alvegård, Thor, et al.
(författare)
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Cellular DNA content and prognosis of high-grade soft tissue sarcoma: the Scandinavian Sarcoma Group experience
- 1990
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Ingår i: Journal of Clinical Oncology. - 1527-7755. ; 8:3, s. 538-547
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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. |
- Choong, P F, et al.
(författare)
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Prognostic value of Ki-67 expression in 182 soft tissue sarcomas. Proliferation--a marker of metastasis?
- 1994
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Ingår i: APMIS : acta pathologica, microbiologica, et immunologica Scandinavica. - 1600-0463. ; 102:12, s. 915-924
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Tidskriftsartikel (refereegranskat)abstract
- Soft tissue sarcomas (STS) are characterized by deregulated proliferation. Ki-67 is a cell cycle antigen which may be elevated in proliferative states. We analysed Ki-67 expression in fixed and embedded tissues from STS in order to examine associations between proliferation, primary tumour characteristics, and metastasis. One hundred and eighty-two adult patients with trunk wall or extremity STS were treated at our institution between 1980 and 1992 (35 developed local recurrence and 56 developed metastases). Median follow-up time for survivors was 6 years (1-13). We used a semiquantitative score to the assess percentage of Ki-67-positive cells: < or = 10% (n = 86), > 10-25% (n = 57), > 25-50% (n = 30), > 50-75% (n = 7), > 75-100% (n = 2). Increasing Ki-67 expression correlated positively with tumour size, malignancy grade, necrosis, vascular invasion, S-phase fraction, and metastasis. A Ki-67 index Ki-D < or = 10% (n = 86) and > 10% (n = 96) defined two groups who had 84% and 56% 3-year metastasis-free survival (p = 0.0001), respectively. Tumours with Ki-D > 10 were typically large, high grade, necrotic, DNA aneuploid, and had intravascular invasion and a higher S-phase fraction. Ki-67 expression may be helpful in predicting survival of patients with soft tissue sarcomas.
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| 3. |
- Dreinhofer, KE, et al.
(författare)
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DNA ploidy in soft tissue sarcoma: Comparison of flow and image cytometry with clinical follow-up in 93 patients : comparison of flow and image cytometry with clinical follow-up in 93 patients
- 2002
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Ingår i: Cytometry. - : Wiley. - 0196-4763. ; 50:1, s. 19-24
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Tidskriftsartikel (refereegranskat)abstract
- In soft tissue sarcoma, the prognostic importance of DNA ploidy status is limited. One possible explanation may be technical; small nondiploid stemlines will he diluted in relation to the presence of normal diploid cells and may not be detected by flow cytometry (FCM). We assessed DNA ploidy status in 93 tumors with both FCM and image cytometry (ICM). ICM may permit the exclusion of nonrelevant cells. The ability of the two methods to detect nondiploid stemlines was compared, as were the prognostic consequences. The patients (54 males) had a median age of 69 years. Surgical procedures were performed on all patients. None of the patients had received preoperative radiotherapy or chemotherapy. FCM and ICM were performed with standard methods. The prognostic value was assessed with univariate and multivariate analysis. In 82 of the 93 tumors, a concordant ploidy status by FCM and ICM was found. In 5 FCM type 1-2 tumors (diploid), the identification of nondiploid stemlines by ICM did not influence the metastatic rates. Increasing tumor size, histotype other than liposarcoma, increasing malignancy grade, tumor necrosis, and ICM nondiploidy were univariate prognostic factors for metastasis. In a multivariate analysis, only tumor size larger than 9 cm was a prognostic factor. In about 10% of the tumors, a discrepancy between FCM and ICM ploidy status was found, but we could not find a consistent prognostic consequence of this. Neither FCM nor ICM ploidy status was an independent prognostic factor. (C) 2002 Wiley-Liss, Inc.
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| 4. |
- Gustafson, Pelle, et al.
(författare)
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Flow cytometric S-phase fraction in soft-tissue sarcoma: prognostic importance analysed in 160 patients
- 1997
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Ingår i: British Journal of Cancer. - 1532-1827. ; 75:1, s. 94-100
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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.
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| 5. |
- Gustafson, Pelle, et al.
(författare)
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Liposarcoma: a population-based epidemiologic and prognostic study of features of 43 patients, including tumor DNA content
- 1993
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 55:4, s. 541-546
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Tidskriftsartikel (refereegranskat)abstract
- Different conceptions exist regarding the epidemiology and prognosis of liposarcoma, and several classification systems are in use. We analyzed a population-based, 25-year series of 43 patients with liposarcoma of the extremity or trunk wall. Follow-up was complete. The annual incidence was 0.12/10(5). The thigh was the most common location. One of 6 tumors was subcutaneous. Deep-seated tumors were larger than s.c. tumors. Among the 42 surgically treated patients, grade II (4-grade scale) was the most common malignancy grade. Four tumors were well-differentiated, 24 were predominantly myxoid, 4 predominantly round-cell, and 10 were predominantly of pleomorphic type. The 5-year metastasis-free survival rate was 69%. By univariate analysis increasing malignancy grade, tumor necrosis, vascular invasion, mitotic count, subtype other than well-differentiated, and high cellularity were prognostic for metastatic disease. However, in the multivariate analysis only tumor necrosis was an independent risk factor. Tumor necrosis should be considered when prognosis of liposarcoma of the extremity and trunk wall is evaluated.
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| 6. |
- Gustafson, Pelle, et al.
(författare)
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Soft tissue leiomyosarcoma. A population-based epidemiologic and prognostic study of 48 patients, including cellular DNA content
- 1992
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Ingår i: Cancer. - 1097-0142. ; 70:1, s. 114-119
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND. Leiomyosarcoma of soft tissue is a rare tumor. There are different opinions regarding epidemiology and prognosis. METHODS. Epidemiology and prognosis were analyzed in a consecutive, population-based series of 48 patients with subcutaneous and deep-seated leiomyosarcoma in the extremities and trunk wall with a complete follow-up of a minimum of 3 years. Cutaneous tumors were not included. RESULTS. The annual incidence was 0.13/10(5). The ratio of men to women was 1.2, and the median age was 65 years. The thigh was the most common location. Almost half of the tumors were subcutaneous. The median tumor size was 6 cm (range, 1-25 cm). All patients were treated with surgery, and in 19 cases it was combined with adjuvant radiation therapy or chemotherapy. The cumulative 5-year survival rate was 64%. Multivariate analysis indicated that age of 60 years or greater (relative risk [RR] = 8) and intratumoral vascular invasion (RR = 4) were independent risk factors for death resulting from tumor. DNA aneuploidy (RR = 4) and tumor necrosis (RR = 3) were associated with poor prognosis, but did not reach statistic significance. CONCLUSIONS. Advanced age, vascular invasion, and DNA aneuploidy could be used to identify prognostic subgroups.
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| 7. |
- Mandahl, Nils, et al.
(författare)
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Comparative cytogenetic and DNA flow cytometric analysis of 150 bone and soft-tissue tumors
- 1993
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 53:3, s. 358-364
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Tidskriftsartikel (refereegranskat)abstract
- Samples from 48 benign and 102 malignant bone and soft-tissue tumors were analyzed cytogenetically and by DNA flow cytometry. Clonal chromosome abnormalities were found in 82 tumors and normal karyotypes in 68; 61 tumors were DNA-non-diploid and 89 were diploid. The cytogenetically abnormal tumors were used for comparison between the 2 types of investigation; 45 of these tumors were DNA-diploid and 37 were DNA-non-diploid. There was, with few exceptions, good correspondence between the quantitative estimates of genomic changes by the 2 methods, indicating that the cells cytogenetically analyzed from short-term cultures are representative of the in vivo cell populations. Discrepancies were primarily found in cases with indexes above 1.5, in which the DNA index was higher than the chromosome index. The chromosome analysis suggested that skewed stemline (G0/G1) peaks in the diploid region in DNA histograms indicate the presence of cell populations with small net quantitative genomic changes, although not all such populations were detected by DNA flow cytometric analysis. The view that one of the peaks in bimodal stemline DNA histograms with narrow peaks represents a non-diploid cell population was also corroborated. On average, the cell populations giving rise to double stemlines in DNA histograms showed quantitatively larger genomic changes than those that gave rise to broad or skewed diploid G0/G1 peaks. The findings indicate that these histogram profiles are not artifactual but reflect chromosomal changes in the tumor parenchyma.
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| 8. |
- Nilbert, Mef, et al.
(författare)
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Complex karyotypic changes, including rearrangements of 12q13 and 14q24, in two leiomyosarcomas
- 1990
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Ingår i: Cancer Genetics and Cytogenetics. - 0165-4608. ; 48:2, s. 217-223
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 9. |
- Seinen, Jojanneke M, et al.
(författare)
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Prognostic value of proliferation in pleomorphic soft tissue sarcomas: a new look at an old measure.
- 2012
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Ingår i: Human Pathology. - : Elsevier BV. - 1532-8392 .- 0046-8177.
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Tidskriftsartikel (refereegranskat)abstract
- Though proliferation has repeatedly shown a prognostic role in sarcomas, it has not reached clinical application. We performed a comprehensive evaluation of the prognostic role of 5 proliferation measures in a large series of soft tissue sarcomas of the extremities and the trunk wall. One hundred ninety-six primary soft tissue sarcomas of the extremities and the trunk wall were subjected to DNA flow cytometry for quantification of S-phase fraction and to immunohistochemical evaluation of Ki-67, Top2a, p21, and p27Kip1. In univariate analysis, positive expression of Ki-67 (hazard ratio = 4.5, CI = 1.6-12.1), Top2a (hazard ratio = 2.2, CI = 1.2-3.5) and high S-phase fraction (hazard ratio = 1.8, CI = 1.2-3.7) significantly correlated with risk for metastasis. When combined with currently used prognostic factors, Ki-67, S-phase fraction and Top2a fraction contributed to refined identification of prognostic risk groups. Proliferation, as assessed by expression of Ki-67 and Top2a and evaluation of S-phase fraction and applied to statistical decision-tree models, provides prognostic information in soft tissue sarcomas of the extremity and trunk wall. Though proliferation contributes independently to currently applied prognosticators, its role is particularly strong when few other factors are available, which suggests a role in preoperative decision-making related to identification of high-risk individuals who would benefit from neoadjuvant therapy.
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