| 1. |
- Carneiro, Ana, et al.
(författare)
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A prognostic model for soft tissue sarcoma of the extremities and trunk wall based on size, vascular invasion, necrosis, and growth pattern.
- 2011
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Ingår i: Cancer. - : Wiley. - 1097-0142 .- 0008-543X. ; Dec, s. 1279-1287
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND:: In soft tissue sarcoma, better distinction of high-risk and low-risk patients is needed to individualize treatment and improve survival. Prognostic systems used in clinical practice identify high-risk patients based on various factors, including age, tumor size and depth, histological type, necrosis, and grade. METHODS:: Whole-tumor sections from 239 soft tissue sarcomas of the extremities were reviewed for the following prognostic factors: size, vascular invasion, necrosis, and growth pattern. A new prognostic model, referred to as SING (Size, Invasion, Necrosis, Growth), was established and compared with other clinically applied systems. RESULTS:: Size, vascular invasion, necrosis, and peripheral tumor growth pattern provided independent prognostic information with hazard ratios of 2.2-2.6 for development of metastases in multivariate analysis. When these factors were combined into the prognostic model SING, high risk of metastasis was predicted with a sensitivity of 74% and a specificity of 85%. Moreover, the prognostic performance of SING compared favorably with other widely used systems. CONCLUSIONS:: SING represents a promising prognostic model, and vascular invasion and tumor growth pattern should be considered in soft tissue sarcoma prognostication. Cancer 2010. © 2010 American Cancer Society.
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| 2. |
- Carneiro, Ana, et al.
(författare)
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Ezrin expression predicts local recurrence and development of metastases in soft tissue sarcomas.
- 2011
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Ingår i: Journal of Clinical Pathology. - : BMJ. - 1472-4146 .- 0021-9746. ; 64, s. 689-694
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Tidskriftsartikel (refereegranskat)abstract
- Background Ezrin is a cytoskeletal protein involved in tumour growth and invasion. Ezrin expression has been suggested to play a role in metastasis in paediatricosteosarcoma and rhabdomyosarcoma. Aim To evaluate the prognostic role of ezrin in a large series of soft tissue sarcoma of the extremities and trunk wall. Methods Ezrin expression was evaluated by immunohistochemistry on tissue microarrays from a mixed series of 256 soft tissue sarcomas. The expression patterns were correlated to local recurrence and metastasis as well as to established prognostic factors in soft tissue sarcoma. Results Increased ezrin expression predicted development of metastasis (HR=1.8, 95% CI 1.1 to 2.8; p=0.007) and local recurrence, also after adjustment for surgical margin (HR=2.4, 95% CI 1.4 to 4.3; p=0.02). Correlations to established prognostic factors showed strong associations between ezrin and necrosis (OR=3.9, p<0.0001) and ezrin and growth pattern (OR=3.1, p=0.03). Conclusions Ezrin independently predicts development of local recurrences and metastases in soft tissue sarcomas. The possibility of preoperative evaluation makes ezrin a potential marker for identification of high-risk sarcoma patients who would benefit from neoadjuvant therapy.
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| 3. |
- Carneiro, Ana, et al.
(författare)
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Indistinguishable genomic profiles and shared prognostic markers in undifferentiated pleomorphic sarcoma and leiomyosarcoma: different sides of a single coin?
- 2009
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Ingår i: Laboratory Investigation. - : Elsevier BV. - 1530-0307 .- 0023-6837. ; 89, s. 668-675
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Tidskriftsartikel (refereegranskat)abstract
- Soft tissue sarcoma (STS) diagnostics and prognostics are challenging, particularly in highly malignant and pleomorphic subtypes such as undifferentiated pleomorphic sarcoma (UPS) and leiomyosarcoma (LMS). We applied 32K BAC arrays and gene expression profiling to 18 extremity soft tissue LMS and 31 extremity soft tissue UPS with the aim of identifying molecular subtype signatures and genomic prognostic markers. Both the gains/losses and gene expression signatures revealed striking similarities between UPS and LMS, which were indistinguishable using unsupervised hierarchical cluster analysis and significance analysis for microarrays. Gene expression analysis revealed just nine genes, among them tropomyosin beta, which were differentially expressed. Loss of 4q31 (encompassing the SMAD1 locus), loss of 18q22, and tumor necrosis were identified as independent predictors of metastasis in multivariate stepwise Cox regression analysis. Combined analysis applying loss of 4q31 and 18q22 and the presence of necrosis improved the area under receiver operating characteristic curve for metastasis prediction from 0.64 to 0.86. The extensive genetic similarities between extremity soft tissue UPS and LMS suggest a shared lineage of these STS subtypes and the new and independent genetic prognosticators identified hold promise for refined prognostic determination in high-grade, genetically complex STS.Laboratory Investigation advance online publication, 16 March 2009; doi:10.1038/labinvest.2009.18.
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| 4. |
- Fernebro, Josefin, et al.
(författare)
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Genetic profiling differentiates second primary tumors from metastases in adult metachronous soft tissue sarcoma.
- 2008
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Ingår i: Sarcoma. - : Hindawi Limited. - 1357-714X .- 1369-1643. ; 2008:2009 Feb 2
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Tidskriftsartikel (refereegranskat)abstract
- Purpose. Patients with soft tissue sarcomas (STS) are at increased risk of second primary malignancies, including a second STS, but distinction between metastases and a second primary STS is difficult. Patients and Methods. Array-based comparative genomic hybridization (aCGH) was applied to 30 multiple STS of the extremities and the trunk wall from 13 patients. Different histotypes were present with malignant fibrous histiocytomas/undifferentiated pleomorphic sarcomas being the predominant subtype. Results. aCGH profiling revealed genetic complexity with multiple gains and losses in all tumors. In an unsupervised hierarchical cluster analysis, similar genomic profiles and close clustering between the first and subsequent STS were identified in 5 cases, suggesting metastatic disease, whereas the tumors from the remaining 8 patients did not cluster and showed only weak pairwise correlation, suggesting development of second primary STS. Discussion. The similarities and dissimilarities identified in the first and second STS suggest that genetic profiles can be used to distinguish soft tissue metastases from second primary STS. The demonstration of genetically different soft tissue sarcomas in the same patient suggests independent tumor origin and serves as a reminder to consider development of second primary STS, which has prognostic and therapeutic implications.
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| 5. |
- 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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