| 1. |
- Ahlén, J, et al.
(författare)
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Malignant Fibrous Histiocytoma, Aggressive Fibromatosis and Benign Fibrous Tumors Express mRNA for the Metalloproteinase Inducer EMMPRIN and the Metalloproteinases MMP-2 and MT1-MMP
- 2001
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Ingår i: Sarcoma. - : Hindawi Limited. - 1357-714X .- 1369-1643. ; 5:3, s. 143-9
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Tidskriftsartikel (refereegranskat)abstract
- Purpose:Extracellular matrix metalloproteinase inducer (EMMPRIN) has been shown to stimulate fibroblasts to production of matrix metalloproteinases (MMPs). MMPs comprise a family of proteolytic enzymes implicated in the degradation of extracellular matrix which has been proposed to be one of the essential steps in tumor invasion and metastases. In the present study we investigated the expression and location of mRNAs forEMMPRIN, matrix metalloproteinase-2 (MMP-2), and membrane-type 1 matrix metalloproteinase (MT1-MMP) in mesenchymal tumors with different tendencies to recur or metastasize.Subjects:Eight malignant fibrous histiocytomas (MFH), seven aggressive fibromatosis (AF), and six benign fibrous tumors (BF).Method:The mRNA-expression ofEMMPRIN,MMP-2andMT1-MMPwere studied using mRNAin situhybridization technique.Results:The mRNA-expression ofEMMPRIN,MMP-2andMT1-MMPrespectively were found at varying frequency and level in all tumor types. The mRNAs corresponding toEMMPRINandMMP-2were seen in neoplastic cells as well as in endothelial cells both inside and outside the tumor pseudo-capsule, whereasMT1-MMPwas seen only within the tumors. The estimated mRNA levels ofEMMPRINandMMP-2covariated significantly. Overall, the highest expression was found in the MFH tumors and the lowest levels in the BF tumors.Discussion:These findings suggest that the MMP-inducerEMMPRINand the extracellular matrix degrading system involving the metalloproteinasesMMP-2andMT1-MMPis frequently activated in mesenchymal tumors. The covariation betweenEMMPRINandMMP-2support previous findings that EMMPRIN may be an inducer of MMP-2. The high levels ofMMP-2mRNA in MFH indicate a relationship between the proteolytic activity ofMMP-2and the tumor aggressiveness.
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| 2. |
- Ericson Lindquist, Kajsa, et al.
(författare)
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Immunohistochemical Loss of the DNA Mismatch Repair Proteins MSH2 and MSH6 in Malignant Fibrous Histiocytomas.
- 2004
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Ingår i: Sarcoma. - 1357-714X. ; 8:4, s. 123-127
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Soft tissue sarcomas (STS) account for less than 1% of all malignancies and constitute a heterogeneous tumor entity in which malignant fibrous histiocytomas (MFH) represent one-third and are characterized by a lack of type-specific differentiation. A defective mismatch repair (MMR) system cause the familial cancer syndrome hereditary non-polyposis colorectal cancer (HNPCC), and since occasional MFH have been described in HNPCC patients we assessed the contribution of defective MMR to the development of MFH.Methods: MMR status was characterized in a series of 209 histopathologically reviewed MFH. Tissue microarray sections from the tumors were immunohistochemically stained for the MMR proteins MLH1, MSH2 and MSH6, and cases with aberrant staining were further characterized for microsatellite instability.Results and Discussion: Two of the 209 STS-a storiform-pleomorphic MFH and a myxofibrosarcoma-showed concomitant loss of MSH2 and MSH6, but retained staining for MLH1 on both cases. The myxoid tumor also had a microsatellite unstable phenotype. These findings, together with previous observations of defective MMR in pleomorphic STS, indicate that these tumors may be part of the HNPCC-associated tumor spectrum and demonstrate that MMR defects occur in a small subset of STS.
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| 3. |
- Fernebro, Josefin, et al.
(författare)
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Focus on the tumor periphery in MRI evaluation of soft tissue sarcoma: infiltrative growth signifies poor prognosis
- 2006
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Ingår i: Sarcoma. - 1357-714X. ; 2006, s. 21251-21251
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Tidskriftsartikel (refereegranskat)abstract
- Purpose. Infiltrative microscopical peripheral growth of soft tissue sarcomas (STS) has been shown to be of prognostic importance and preoperative risk stratification could individualize neoadjuvant treatment. Patients and methods. We assessed peripheral tumour growth pattern on preoperative MRI from 78 STS. The findings were correlated to histopathology and to outcome. Results. The MRI-based peripheral tumour growth pattern was classified as pushing in 34 tumours, focally infiltrative in 25, and diffusely infiltrative in 19. All tumours with diffuse infiltration on MRI also showed microscopical infiltration, whereas MRI failed to identify infiltration in two-thirds of the microscopically infiltrative tumours. Diffusely infiltrative growth on MRI gave a 2.5 times increased risk of metastases (P = .01) and a 3.7 times higher risk of local recurrence (P = .02). Discussion. Based on this observation we suggest that MRI evaluation of STS should focus on the peripheral tumour growth pattern since it adds prognostic information of value for decisions on neoadjuvant therapies.
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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. |
- Jönsson, Peter, et al.
(författare)
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Chest wall sarcoma: outcome in 22 patients after resection requiring thoracic cage reconstruction.
- 1998
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Ingår i: Sarcoma. - : Hindawi Limited. - 1357-714X .- 1369-1643. ; 2:3-4, s. 143-147
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Tidskriftsartikel (refereegranskat)abstract
- Purpose. To evaluate the outcome after resection of malignant chest wall sarcoma, requiring reconstruction of the chest wall.Subjects. Twenty-two patients, 15 with primary tumours, were operated on in our institution between 1983 and 1996. Four patients underwent surgery after a previous intralesional or marginal excision and three patients because of a local recurrence.Methods. The tumour was resected 'en bloc', including skin, muscle and thoracic skeleton. When necessary, adjacent organs invaded by the tumour, such as lung, pericardium and diaphragm, were also removed to obtain a wide margin. Reconstruction of the chest wall was performed with Marlex mesh (n=9), methylmethacrylate cement (n=2) or a Marlex methylmethacrylate 'sandwich' (n=11).Results. The median tumour size was 9.5 (2-20) cm. The most common type of tumour was chondrosarcoma (12 cases). No patient died in hospital. Five patients required reoperation because of complications, two patients because of loosening of the acrylate prosthesis, two because of necrosis of soft tissue coverage and one was reoperated because of bleeding. Four patients died of generalized tumour disease between 5 and 77 months after surgery and one patient died of a local recurrence 32 months after the primary operation. Seventeen patients are alive, with a median follow-up of 36 (4-162) months. Microscopic radicality (negative margin) was achieved in 17 patients but 5 of these had local recurrences. Two of five patients with positive margins had a local recurrence of the tumour. Of the seven patients with local recurrences, two also developed metastases.Discussion. Large chest wall sarcomas can be successfully resected and the chest wall reconstructed with low morbidity and mortality.
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| 6. |
- Kåbjörn-Gustafsson, Christina, et al.
(författare)
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Cell Senescence in Myxoid/Round Cell Liposarcoma
- 2014
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Ingår i: Sarcoma. - : Hindawi Limited. - 1357-714X .- 1369-1643. ; 2014:Article ID 208786
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Tidskriftsartikel (refereegranskat)abstract
- Myxoid/round cell liposarcoma (MLS/RCLS) is the second most common liposarcoma type and characterized by the fusion oncogenes FUS-DDIT3 or EWSR1-DDIT3. Previous analysis of cell cycle regulatory proteins revealed a prominent expression of G1-cyclins, cyclin dependent kinases and their inhibitors but very few cells progressing through the G1/S boundary. Here, we extend the investigation to proteins involved in cell senescence in an immunohistochemistry based study of 17 MLS/RCLS cases. Large subpopulations of tumor cells expressed the RBL2 pocket protein and senescence associated heterochromatin 1γ and IL8 receptor β. We conclude that MLS/RCLS tissues contain major populations of senescent tumor cells and this may explain the slow growth rate of this tumor type.
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| 7. |
- Kåbjörn-Gustafsson, Christina, et al.
(författare)
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DDIT3 Expression in Liposarcoma Development
- 2014
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Ingår i: Sarcoma. - : Hindawi Limited. - 1357-714X .- 1369-1643. ; 2014
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Tidskriftsartikel (refereegranskat)abstract
- Liposarcomas are mesenchymal tumors containing variable numbers of lipoblasts or adipocytes. The most common entities, well differentiated/dedifferentiated liposarcoma (WDLS/DDLS) and myxoid/round cell liposarcoma (MLS/RCLS), are both characterized by genetic rearrangements that affect the expression of the transcription factor DDIT3. DDIT3 induces liposarcoma morphology when ectopically expressed in a human fibrosarcoma. The role of DDIT3 in lipomatous tumors is, however, unclear. We have analyzed the expression of DDIT3 in 37 cases of liposarcoma (WDLS/DDLS n = 10, MLS/RCLS n = 16, and pleomorphic liposarcomas (PLS) n = 11) and 11 cases of common benign lipomas. Major cell subpopulations of WDLS/DDLS and MLS/RCLS tumors were found to express DDIT3 or the derived fusion protein, whereas PLS cases showed only a few positive cells. The lipomas contained large subpopulations expressing DDIT3. No correlation between numbers of DDIT3 expressing cells and numbers of lipoblasts/adipocytes was found. In vitro adipogenic treatment of two DDIT3 expressing cell lines induced lipid accumulation in small subpopulations only. Our results suggest a dual, promoting and limiting, role for DDIT3 in the formation of lipoblasts and liposarcoma morphology.
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| 8. |
- Nilsson, G, et al.
(författare)
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Detection of EWS/FLI-1 by Immunostaining. An Adjunctive Tool in Diagnosis of Ewing's Sarcoma and Primitive Neuroectodermal Tumour on Cytological Samples and Paraffin-Embedded Archival Material
- 1999
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Ingår i: Sarcoma. - : Hindawi Limited. - 1357-714X .- 1369-1643. ; 3:1, s. 25-32
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Tidskriftsartikel (refereegranskat)abstract
- Purpose.Recently we showed that the 68-kDa fusion protein derived from theEWS/FLI1hybrid gene can be specifically detected by Western blotting using a polyclonal antibody to the C-terminal of FLI1 on biopsy material from Ewing's sarcoma. The aim of this study was to investigate whether this antibody also could be used for immunocytochemistry and immunohistochemistry in diagnosis of Ewing's sarcoma.Methods.Immunostaining on paraffin-embedded archival material, fine-needle aspirates and tumour touch imprints from Ewing's sarcomas and primitive neuroectodermal tumours (PNET) for detection of the fusion protein was performed. Most cases were also analysed by Western blotting.Tumours of differential diagnostic importance were also included.Results. Eighty per cent (12/15 cases) of the Ewing tumours exhibited a positive immunoreactivity for the FLI1 antibody. The signal was mainly localised in the nuclei of the tumour cells, which seems reasonable sinceEWS/FLI1is a transcription factor. The signal was found to be specific since it did not appear when the blocking peptide was added to the antibody solution.Moreover, two other types of small-round cell tumours (i.e. neuroblastoma and alveolar rhabdomyosarcoma) were negative as well as most normal tissues.Discussion.Immunostaining of histological and cytological specimens with the FLI1 antibody can be of diagnostic relevance in Ewing tumours carrying t(11;22).The absence of immunoreactivity in non-Ewing cells is most likely due to a low expression of the wild-type FLI1 protein.
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| 9. |
- Nordemar, D, et al.
(författare)
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Intra-Articular Synovial Sarcomas: Incidence and Differentiating Features from Localized Pigmented Villonodular Synovitis
- 2015
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Ingår i: Sarcoma. - : Hindawi Limited. - 1357-714X .- 1369-1643. ; 2015, s. 903873-
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Tidskriftsartikel (refereegranskat)abstract
- Purpose.To determine the incidence of intra-articular synovial sarcomas and investigate if any radiological variables can differentiate them from localized (unifocal) pigmented villonodular synovitis (PVNS) and if multivariate data analysis could be used as a complementary clinical tool.Methods.Magnetic resonance images and radiographs of 7 cases of intra-articular synovial sarcomas and 14 cases of localized PVNS were blindedly reviewed. Variables analyzed were size, extra-articular growth, tumor border, blooming, calcification, contrast media enhancement, effusion, bowl of grapes sign, triple signal intensity sign, synovial low signal intensity, synovitis, age, and gender. Univariate and multivariate data analysis, the method of partial least squares-discriminant analysis (PLS-DA), were used. Register data on all synovial sarcomas were extracted for comparison.Results.The incidence of intra-articular synovial sarcomas was 3%. PLS-DA showed that age, effusion, size, and gender were the most important factors for discrimination between sarcomas and localized PVNS. No sarcomas were misclassified as PVNS with PLS-DA, while some PVNS were misclassified as sarcomas.Conclusions.The most important variables in differentiating intra-articular sarcomas from localized PVNS were age, effusion, size, and gender. Multivariate data analysis can be helpful as additive information to avoid a biopsy, if the tumor is classified as most likely being PVNS.
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| 10. |
- Rechl, Victor, et al.
(författare)
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Factors Influencing the Outcome of Patients with Primary Ewing Sarcoma of the Sacrum.
- 2024
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Ingår i: Sarcoma. - 1357-714X. ; 2024
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Tidskriftsartikel (refereegranskat)abstract
- Ewing sarcoma (EwS) is a rare and highly malignant bone tumor primarily affecting children, adolescents, and young adults. The pelvis, trunk, and lower extremities are the most common sites, while EwS of the sacrum as a primary site is very rare, and only few studies focusing on this location are published. Due to the anatomical condition, local treatment is challenging in sacral malignancies. We analyzed factors that might influence the outcome of patients suffering from sacral EwS.We retrospectively analyzed data of the GPOH EURO-E.W.I.N.G 99 trial and the EWING 2008 trial, with a cohort of 124 patients with localized or metastatic sacral EwS. The study endpoints were overall survival (OS) and event-free survival (EFS). OS and EFS were calculated using the Kaplan-Meier method, and univariate comparisons were estimated using the log-rank test. Hazard ratios (HRs) with respective 95% confidence intervals (CIs) were estimated in a multivariable Cox regression model.The presence of metastases (3y-EFS: 0.33 vs. 0.68; P < 0.001; HR=3.4, 95% CI 1.7 to 6.6; 3y-OS: 0.48 vs. 0.85; P < 0.001; HR=4.23, 95% CI 1.8 to 9.7), large tumor volume (≥200ml) (3y-EFS: 0.36 vs. 0.69; P=0.02; HR=2.1, 95% CI 1.1 to 4.0; 3y-OS: 0.42 vs. 0.73; P=0.04; HR=2.1, 95% CI 1.03 to 4.5), and age ≥18years (3y-EFS: 0.41 vs. 0.60; P=0.02; HR=2.6, 95% CI 1.3 to 5.2; 3y-OS: 0.294 vs. 0.59; P=0.01; HR=2.92, 95% CI 1.29 to 6.6) were revealed as adverse prognostic factors.Young age seems to positively influence patients` survival, especially in patients with primary metastatic disease. In this context, our results support other studies, stating that older age has a negative impact on survival. Tumor volume, metastases, and the type of local therapy modality have an impact on the outcome of sacral EwS. Level of evidence: Level 2. This trial is registered with NCT00020566 and NCT00987636.
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| 11. |
- Seinen, Jojanneke, et al.
(författare)
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Delays in the management of retroperitoneal sarcomas.
- 2010
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Ingår i: Sarcoma. - : Hindawi Limited. - 1357-714X .- 1369-1643. ; 2010
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Tidskriftsartikel (refereegranskat)abstract
- Retroperitoneal sarcomas are rare and treatment should optimally be centralized. Despite successful centralization with 90% of the patients referred prior to surgery, delays occur, which led us to assess lead times in a population-based series. Method. Patients diagnosed with retroperitoneal sarcoma in the southern Sweden health care region 2003-2009 were eligible for the study. Data on referrals and diagnostic investigations were collected from clinical files from primary health care, local hospitals, and from the sarcoma centre. Lead times were divided into patient delays and health care delays caused by primary health care, local hospitals, or procedures at the sarcoma centre. Results. Complete data were available from 33 patients and demonstrated a median patient delay of 23 days (0-17 months) and median health care delay of 94 days (1-40 months) with delays of median 15 days at the general practitioner, 36 days at local hospitals, and 55 days at the sarcoma centre. Conclusion. Centralization per se is not sufficient for optimized and efficient management. Our findings suggest that delays can be minimized by direct referral of patients from primary health care to sarcoma centers and indicate that development of coordinated diagnostic packages could shorten delays at the sarcoma centre.
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| 12. |
- Söderlund, V, et al.
(författare)
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Diagnosis of high-grade osteosarcoma by radiology and cytology: a retrospective study of 52 cases
- 2004
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Ingår i: Sarcoma. - : Hindawi Limited. - 1357-714X .- 1369-1643. ; 8:1, s. 31-6
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Tidskriftsartikel (refereegranskat)abstract
- The diagnostic value of combined radiology and fine needle aspiration cytology (FNAC) was retrospectively assessed in a consecutive series of 52 patients with high-grade osteosarcoma. The series was divided into typical and atypical osteosarcomas according to radiological features and site. Thirty-two of 33 radiologically typical osteosarcoma cases were correctly diagnosed by cytology; one lesion was diagnosed as sarcoma NOS. Nineteen osteosarcoma cases were radiographically atypical. Six of these were diagnosed as osteosarcoma and another six as sarcoma NOS. In three cases another type of sarcoma was suggested. One case was falsely classified as benign. FNAC of three cases were non-diagnostic. Overall, the diagnostic difficulties pertained to the radiologically atypical cases. Notably, four of these also posed considerable difficulties in the histopathological assessment prompting external consultation. Our study suggests that open biopsy can be obviated in high-grade osteosarcomas exhibiting typical radiological features, i.e., in two-thirds.
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| 13. |
- Söderlund, V, et al.
(författare)
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Representativeness of radiologically guided fine-needle aspiration biopsy of bone lesions
- 2002
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Ingår i: Sarcoma. - : Hindawi Limited. - 1357-714X .- 1369-1643. ; 6:2, s. 61-8
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Tidskriftsartikel (refereegranskat)abstract
- The consistency of the cellular yield as obtained by radiologically guided fine-needle aspiration biopsy (FNAB) was investigated in 29 cases with bone lesions. Aspirates from three different sites of the same lesion were analysed randomly and independently by two cytologists unaware of the clinical and radiological findings.The series was grouped cytologically into four categories: (1) benign, (2) sarcoma, (3) other malignancy, (4) non-conclusive. A lesion was considered cytologically homogenous, when all three aspirates were identically categorised. Among 29 lesions, 13 and 12, respectively, were assessed as homogeneous by the two cytologists. In the remaining lesions, heterogeneity almost exclusively pertained to the mixture of conclusive and non-conclusive aspirates. An alternative diagnosis was suggested in one case by each cytologist. Comparison of the two cytologists' assessments showed that 21 cases were compliant, i.e., no inter-observer difference in 63 out of 87 aspirates. In the remaining eight cases (24 aspirates), non-compliance was mainly due to differences between the cytologists in the ratio of conclusive versus non-conclusive aspirates. Only the analysis of one and the same aspirate resulted in two different diagnoses. A correct diagnosis was given by the cytologists in 22 and 23 cases, incorrect in two and non-conclusive in five and four, respectively.Our cytological study of bone lesions, albeit limited, suggests that true tumour heterogeneity is rare. The non-compliance between the two cytologists and the diagnostic difficulties should mainly be attributed to the blind, random approach of the study.The main problem of FNAB pertains to the high rate of non-conclusive aspirates.This, however, does not entail an increased risk of incorrect diagnosis, but rather prompts repeat FNAB.
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| 14. |
- Åkerman, Måns
(författare)
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Fine-needle aspiration cytology of soft tissue sarcoma: benefits and limitations.
- 1998
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Ingår i: Sarcoma. - : Hindawi Limited. - 1357-714X .- 1369-1643. ; 2:3-4, s. 155-161
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Tidskriftsartikel (refereegranskat)abstract
- Purpose. Examine the benefits and limitations of fine-needle aspiration cytology (FNA) used as the definitive diagnostic method before treatment.Method. Review of the 25 year experience at a multidisciplinary musculo-skeletal centre where FNA is the primary diagnostic approach to soft tissue sarcoma in the extremities and trunk wall and the experience of various experts in the field.Results. FNA has several benefits compared with coarse needle or open surgical biopsy. The most important are rapid preliminary diagnosis, no need for hospitalization and anaesthesia, negligible complications and fear for tumour cell spread. With the collected experience gained during the years a reliable diagnosis of sarcoma is the rule in general and specific-type diagnoses are possible in many histotypes, especially when the cytologic examination is supplemented with ancillary diagnostics. The most important limitations are inability to hit small deep-seated sarcoma and some diagnostic pitfalls such as the correct diagnosis of spindle cell neoplasms, variants of benign lipomatous tumours and 'new soft tissue tumour entities'.Discussion. Optimal use of FNA calls for certain requirements such as centralization, experience in soft tissue tumour cytology-histopathology, the FNA technique and close co-operation between the orthopaedic surgeon and cytopathologist.
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