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ABSTRACT: 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.
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.
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.
SING represents a promising prognostic model, and vascular invasion and tumor growth pattern should be considered in soft tissue sarcoma prognostication.
Cancer 03/2011; 117(6):1279-87. · 4.77 Impact Factor
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ABSTRACT: Mesenchymal stromal cells (MSC) are multipotent cells that can be isolated from a number of human tissues. In cancer, MSC have been implicated with tumor growth, invasion, metastasis, drug resistance and were even suggested as possible tumor-initiating cells in osteosarcoma (OS). However, MSC from OS and their possible tumor origin have not yet been thoroughly investigated. Therefore, primary OS mesenchymal progenitors and OS-derived MSC were studied. OS samples contained very high frequencies of mesenchymal progenitor cells as measured by the colony-forming unit fibroblast (CFU-F) assay (median: 1,117 colonies per 10(5) cells, range: 133-3,000, n = 6). This is considerably higher compared to other human tissues such as normal bone marrow (BM) (1.3 ± 0.2 colonies per 10(5) cells, n = 8). OS-derived MSC (OS-MSC) showed normal MSC morphology and expressed the typical MSC surface marker profile (CD105/CD73/CD90/CD44/HLA-classI/CD166 positive, CD45/CD34/CD14/CD19/HLA-DR/CD31 negative). Furthermore, all OS-MSC samples could be differentiated into the osteogenic lineage, and all but one sample into adipocytes and chondrocytes. Genetic analysis of OS-MSC as well as OS-derived spheres showed no tumor-related chromosomal aberrations. OS-MSC expression of markers related to tumor-associated fibroblasts (fibroblast surface protein, alpha-smooth muscle actin, vimentin) was comparable to BM-MSC and OS-MSC growth was considerably affected by tyrosine kinase inhibitors. Taken together, our results demonstrate that normal, non-malignant mesenchymal stroma cells are isolated from OS when MSC culture techniques are applied. OS-MSC represent a major constituent of the tumor microenvironment, and they share many properties with BM-derived MSC.
International Journal of Cancer 09/2010; 129(2):319-30. · 5.44 Impact Factor
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ABSTRACT: Angiosarcoma is a rare complication of breast cancer treatment. In order to define predictors, clinical presentation, and outcome, we characterized a population-based 50-year cohort of angiosarcomas after breast cancer. Clinical data were collected from all females with previous breast cancer who developed angiosarcomas/lymphangiosarcomas on the thoracic wall/upper extremity between 1958 and 2008 in the Southern Swedish health care region. In total, 31 angiosarcomas developed at a median age of 71 years. The patients formed two distinct groups; 14 females treated for breast cancer with radical mastectomy and radiotherapy 1949-1988 developed angiosarcomas in edematous arms (Stewart-Treves syndrome) after median 11 years, and 17 females treated by segmental resection, anti-hormonal treatment and radiotherapy 1980-2005 developed angiosarcomas in the irradiated field on the thoracic wall after median 7.3 years. The clinical presentations were heterogeneous and included hematoma-like lesions, multiple bluish-reddish nodules, and asymptomatic lumps. The overall 5-year survival was 16%. In this population-based cohort, the early angiosarcomas developed in edematous arms after radical mastectomies, whereas more recent cases occurred after a shorter time period in the irradiated fields following breast conserving surgery. We conclude that the clinical presentation of angiosarcomas has changed, parallel with altered treatment principles for breast cancer.
Breast Cancer Research and Treatment 08/2010; 122(3):883-7. · 4.43 Impact Factor
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ABSTRACT: Endothelin (ET)-1 has been implicated in the atherosclerotic process and during inflammation. Similarity in the development process of giant cell arteritis (GCA) and atherosclerosis exists. Several ET receptor antagonists have been developed, principally to target cardiovascular disease states. High doses of corticosteroids currently are used in the treatment of GCA, whereas other treatments are not as reliably effective. The present study was performed to elucidate the role for ET-1, ET(A), and ET(B) receptors in GCA.
Experimental, retrospective immunohistochemical study of temporal arteries using archival formalin-fixed, paraffin-embedded tissue.
The study included 10 patients with GCA and 10 control patients with clinically suspected GCA but diagnosed not to have GCA.
Immunohistochemistry, with anti ET-1, anti-ET(A), and anti-ET(B) antibodies, was performed on formalin-fixed and paraffin-embedded temporal arteries.
Endothelin-1, ET(A), and ET(B) receptor immunostaining intensities were quantified.
Temporal arteries from the patients with GCA showed the typical histologic features, including intimal thickening, disruption or loss of the elastic lamina, and inflammatory infiltrates of lymphocytes, macrophages, and multinucleated giant cells. These features were associated with increased ET-1 and ET(B) receptor immunoreactivity in the medial layer of the temporal arteries and endothelial cells in patients with GCA compared with the controls. The increased ET-1 and ET(B) receptor immunoreactivity occurred in vascular smooth muscle cells (SMCs) and multinucleated giant cells. The ET-1 and ET(B) receptor immunoreactivity correlated with the degree of systemic inflammation. No changes were observed in ET(A) receptor expression in SMCs or endothelial cells compared with controls.
The results suggest a role for ET-1 and ET(B) receptors in GCA. Inhibiting the ET system may provide a corticosteroid-sparing alternative in the treatment of GCA.
Ophthalmology 03/2010; 117(3):628-36. · 5.45 Impact Factor
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ABSTRACT: Currently, giant cell arteritis (GCA) is primarily treated with corticosteroids or immunomodulating agents, but there is interest in identifying other noncorticosteroid alternatives. Similarities exist in the injury pathways between GCA and atherosclerosis. Angiotensin II is a vasoactive peptide involved in vessel inflammation during atherosclerosis, and angiotensin II receptor inhibitors are effective in preventing atherosclerosis. The present study was performed to elucidate the role of angiotensin type 1 (AT(1)) and type 2 (AT(2)) receptors in GCA.
Experimental retrospective immunohistochemical study of temporal arteries using archival formalin-fixed, paraffin-embedded tissue.
Ten patients with GCA and 10 control patients, who were clinically suspected of having GCA but were diagnosed as not having GCA, were included.
Immunohistochemistry, using anti-AT(1) and anti-AT(2) antibodies, was performed on formalin-fixed and paraffin-embedded temporal arteries.
AT(1) and AT(2) receptor immunostaining intensity was quantified.
Hematoxylin-eosin-stained sections of temporal arteries from patients with GCA showed intimal hyperplasia, internal elastic lamina degeneration, and band-shaped infiltrates of inflammatory cells, including lymphocytes, histocytes, and multinucleated giant cells. AT(1) receptor staining was primarily observed in the medial layer of the temporal arteries and was higher in the patients with GCA than in the control patients. This was a result of increased AT(1) receptor immunostaining of both vascular smooth muscle cells and infiltrating inflammatory cells. Only faint immunostaining was seen for AT(2) receptors, primarily in the endothelial cells, and to a lesser extent on the smooth muscle cells. Immunostaining with antibodies for the AT(2) receptor was similar in the patients with GCA and in controls.
These results suggest that AT(1) receptors play a role in the development of GCA. Inhibition of the angiotensin system may thus provide a noncorticosteroid alternative for the treatment of GCA.
The author(s) have no proprietary or commercial interest in any materials discussed in this article.
Ophthalmology 06/2009; 116(5):990-6. · 5.45 Impact Factor
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ABSTRACT: This study aims to determine the diagnostic accuracy of fine-needle aspiration cytology (FNAC) of primary leiomyosarcoma (LMS) of soft tissue and to review diagnostic criteria and adjunctive methods, which can contribute to a confident diagnosis. We evaluated the preoperative FNAC in 89 patients with primary LMS for the following: cytomorphology and correspondence of FNA to histological features of excised tumors and clinical data. In addition, the utility of adjunctive techniques was analyzed and other spindle-cell lesions in the differential diagnoses were discussed. An unequivocal, malignant diagnosis was rendered by FNAC in 78 cases; 74 tumors were diagnosed as sarcoma, of which 31 as LMS or suspicion of LMS. In addition, three smears were labeled as malignant tumor, one as carcinoma metastasis, and three as neurilemmoma. Seven aspirates were inconclusive and one insufficient. On reevaluation, the diagnostic smears in most cases contained tumor cell fascicles with an admixture of dispersed cells or stripped nuclei. The most common cells were spindle cells with elongated, blunt-ended, segmented or fusiform nuclei, and round/polygonal cells, often with rounded or indented nuclei. In addition, 51 cases showed pleomorphic, often multinucleated cells. Osteoclasts, intranuclear vacuoles, and mitoses occurred in 14, 47, and 27 cases, respectively. Thus, most high-grade LMSs have cytologic features that allow diagnosis of sarcoma. Ancillary studies can confirm the diagnosis of LMS and help in the correct interpretation of predominant spindle-cell or epitheloid-cell smears resembling neurilemoma or carcinoma, respectively.
Diagnostic Cytopathology 10/2006; 34(9):597-604. · 1.16 Impact Factor
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ABSTRACT: Adjuvant treatment with adriamycin has been suggested to improve results after liver transplantation for hepatocellular cancer. Here we have applied an animal model for evaluation of treatment with adriamycin and/or cyclosporine A on liver tumour growth. Three chemically induced rat liver tumours with various degree of differentiation were transferred to the spleens of syngenic rats. Each recipient group was divided into four subgroups, treated with adriamycin and/or cyclosporine A or none of the drugs. When the tumour was well differentiated no proliferation was found in any of the subgroups. When the tumour exhibited a more pronounced dysplasia, adriamycin stimulated tumour growth. This effect was further increased by cyclosporine. In the animals transplanted with the most aggressive tumour, adriamycin inhibited tumour growth. When given together with cyclosporine this inhibition was counteracted. These data suggest that adriamycin, especially when given together with cyclosporine, may have a stimulatory effect on liver tumour cell growth.
Transplant International 09/2005; 18(8):992-1000. · 2.92 Impact Factor
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ABSTRACT: The purpose of this study was to evaluate the effects of hepatic vein occlusion by stent-graft used in transjugular intrahepatic portosystemic shunt (TIPS). The experiments were performed in six healthy pigs under general anesthesia. Following percutaneous transhepatic implantation of a port-a-cath in the right hepatic vein, TIPS was created with a stent-graft (Viatorr; W L Gore, Flagstaff, AZ, USA). The outflow from the hepatic vein, blocked by the stent-graft was documented by injection of contrast medium and repeated injections of (99)Tc(m)-labeled human serum albumin through the port-a-cath. After 2 weeks, the outflow was re-evaluated, the pigs were sacrificed, and histopathologic examination of the liver was performed. Occlusion of the hepatic vein by a stent-graft had a short and temporary effect on the outflow. Histopathological examination from the affected liver segment showed no divergent pattern. Stent-grafts used in TIPS block the outflow from the liver vein, but do not have a prolonged circulatory effect and do not affect the liver parenchyma.
CardioVascular and Interventional Radiology 29(1):120-3. · 2.09 Impact Factor
