| 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. |
- Baldetorp, Bo, et al.
(författare)
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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
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Ingår i: Cytometry. - : Wiley. - 0196-4763 .- 1097-0320. ; 13:6, s. 577-585
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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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| 3. |
- Baldetorp, Bo, et al.
(författare)
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Proliferative index obtained by DNA image cytometry. Does it add prognostic information in Auer IV breast cancer?
- 1998
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Ingår i: Analytical and Quantitative Cytology and Histology. - 0884-6812. ; 20:2, s. 144-152
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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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| 4. |
- 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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| 5. |
- 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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| 6. |
- Fernö, Mårten, et al.
(författare)
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Flow cytometric DNA ploidy analysis of soft tissue sarcomas. A comparative study of preoperative fine needle aspirates and postoperative fresh tissues and archival material
- 1990
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Ingår i: Analytical and Quantitative Cytology and Histology. - 0884-6812. ; 12:4, s. 251-258
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 7. |
- 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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| 8. |
- 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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| 9. |
- Gustafson, Pelle, et al.
(författare)
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Prognostic implications of various models for calculation of S-phase fraction in 259 patients with soft tissue sarcoma
- 1999
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Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 1532-1827 .- 0007-0920. ; 79, s. 1205-1209
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Tidskriftsartikel (refereegranskat)abstract
- The S-phase fraction (SPF) in flow cytometric DNA histograms in soft tissue sarcoma (STS) can be calculated in various ways. The traditional planimetric method of Baisch has been shown to be prognostic, but is hampered by a failure rate of around 40%. We therefore tested other models to see if this rate could be decreased with retained prognostic value. In 259 STS of the locomotor system the SPF was calculated according to Baisch and with commercial parametric MultiCycle software using different corrections for background. Using the Baisch model, 159 histograms could be evaluated for SPF. The 5-year metastasis-free survival rate (MFSR) was 0.94 for the low-risk group (defined with SPF), and 0.53 for the high-risk group. In the low-risk group, four of the seven patients who developed metastasis did so after 5 years Using the MultiCycle software, SPF could be calculated in 253 tumours. Depending on type of background correction used, the 5-year MFSR varied between 0.67 and 0.82 for the low-risk group, and between 0.47 and 0.53 for the high-risk group. The late metastasis pattern in the low-risk group was never seen using the MultiCycle software. We conclude that in paraffin archival material, calculation of SPF according to Baisch is preferable in clinical use due to better separation between low-risk and high-risk groups, and also the possibility to identify patients who metastasize late.
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| 10. |
- 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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