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| 2. |
- Styring, Emelie, et al.
(författare)
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Key Roles for MYC, KIT and RET signaling in secondary angiosarcomas.
- 2014
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Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 1532-1827 .- 0007-0920. ; 111:2, s. 407-412
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Tidskriftsartikel (refereegranskat)abstract
- Background:Angiosarcomas may develop as primary tumours of unknown cause or as secondary tumours, most commonly following radiotherapy to the involved field. The different causative agents may be linked to alternate tumorigenesis, which led us to investigate the genetic profiles of morphologically indistinguishable primary and secondary angiosarcomas.Methods:Whole-genome (18k) c-DNA-mediated annealing, selection, extension and ligation analysis was used to genetically profile 26 primary and 29 secondary angiosarcomas. Key findings were thereafter validated using RT-qPCR, immunohistochemistry and validation of the gene signature to an external data set.Results:In total, 103 genes were significantly deregulated between primary and secondary angiosarcomas. Secondary angiosarcomas showed upregulation of MYC, KIT and RET and downregulation of CDKN2C. Functional annotation analysis identified multiple target genes in the receptor protein tyrosine kinase pathway. The results were validated using RT-qPCR and immunohistochemistry. Further, the gene signature was applied to an external data set and, herein, distinguished primary from secondary angiosarcomas.Conclusions:Upregulation of MYC, KIT and RET and downregulation of CDKN2C characterise secondary angiosarcoma, which implies possibilities for diagnostic application and a mechanistic basis for therapeutic evaluation of RET-kinase-inhibitors in these highly aggressive tumours.
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| 4. |
- Boiesen, P, et al.
(författare)
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Histologic grading in breast cancer--reproducibility between seven pathologic departments. South Sweden Breast Cancer Group
- 2000
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Ingår i: Acta Oncologica. - : Informa UK Limited. - 1651-226X .- 0284-186X. ; 39:1, s. 41-45
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Tidskriftsartikel (refereegranskat)abstract
- Histologic grade, including tubular formations, nuclear grade, and mitotic activity, is a well-documented prognostic factor in breast cancer. In comparison with other prognostic parameters, the evaluation of histologic grade is cheap and can be performed, in principle, in all cases of breast cancer. One possible disadvantage is that the evaluation may vary between different pathological departments. The aim of the present work was therefore to study the reproducibility of the histologic grading system by distributing haematoxylin-erythrosin-stained slides from 93 invasive breast cancers to the seven pathology departments within the southern healthcare region of Sweden. The evaluation was performed blindly and without any knowledge of other clinical parameters. In 31% of the cases the same histologic grade was obtained for all departments. The overall mean kappa was 0.54, indicating a moderate reproducibility. Of the three factors included in histologic grade, the agreement was best for tubular formations and poorest for nuclear grade and mitotic activity. The overall moderate reproducibility should be considered when the clinical usefulness of histologic grading is compared with other prognostic instruments.
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| 5. |
- Dahlén, A, et al.
(författare)
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Analysis of the distribution and frequency of trisomy 7 in vivo in synovia from patients with osteoarthritis and pigmented villonodular synovitis
- 2001
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Ingår i: Cancer Genetics and Cytogenetics. - 0165-4608. ; 131:1, s. 19-24
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Tidskriftsartikel (refereegranskat)abstract
- Osteoarthritis (OA) and pigmented villonodular synovitis (PVNS) are disorders associated with trisomy 7. The aim of the present study was to determine the frequency and distribution of the cells with +7 in vivo by analyzing sections of paraffin-embedded synovia from patients affected by OA, PVNS, other forms of synovitis [hemorragic synovitis (HS) and chronic synovitis (CS)], and from individuals without joint disease. Fluorescence in situ hybridization (FISH), using a centromeric probe for chromosome 7, showed that the mean frequency of trisomic nuclei in 5-microm sections was highest in PVNS (9.0%), followed by CS (5.9%), OA (5.6%), and HS (4.6%), whereas trisomic nuclei were rare (0.7%) in normal tissue. When 8-microm sections were studied, the frequencies of trisomic cells in OA and control synovia increased to 6.7% and 1.5%, respectively. Trisomic nuclei were found in all cases, including those for which cytogenetic analysis of short-term cultures had not disclosed any trisomic cells. Overall, the trisomic cells were scattered within the tissue. However, small clusters of cells with +7 were found in three cases. By hematoxylin-eosin staining of the slides used for FISH analysis it could be shown that the clustered trisomic cells were proliferating synoviocytes within villous extensions of the synovial membrane.
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| 6. |
- Domanski, H., et al.
(författare)
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Gaucher's disease in an infant diagnosed by fine needle aspiration of the liver and spleen : A case report
- 1992
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Ingår i: Acta Cytologica. - 0001-5547. ; 36:3, s. 410-412
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Tidskriftsartikel (refereegranskat)abstract
- A case of Gaucher's disease diagnosed by means of fine needle aspiration of the liver and spleen in a 12-month-old boy with hepatosplenomegaly is presented. The diagnosis was based on the finding of large, macrophagelike cells with abundant, pale, fibrillary cytoplasm and small nuclei. The patient had no family history of Gaucher's disease, and the diagnosis was not suspected clinically.
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| 7. |
- Hallor, Karolin H, et al.
(författare)
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Two genetic pathways, t(1;10) and amplification of 3p11-12, in myxoinflammatory fibroblastic sarcoma, haemosiderotic fibrolipomatous tumour, and morphologically similar lesions.
- 2009
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Ingår i: Journal of Pathology. - : Wiley. - 0022-3417 .- 1096-9896. ; 217, s. 716-727
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Tidskriftsartikel (refereegranskat)abstract
- Myxoinflammatory fibroblastic sarcoma (MIFS) is a low-grade malignant neoplasm for which limited genetic information, including a t(1;10)(p22;q24) and amplification of chromosome 3 material, is available. To further characterize these aberrations, we have investigated eight soft tissue sarcomas diagnosed as MIFS, haemosiderotic fibrolipomatous tumour (HFT), myxoid spindle cell/pleomorphic sarcoma with MIFS features, and inflammatory malignant fibrous histiocytoma/undifferentiated pleomorphic sarcoma with prominent inflammation (IMFH) harbouring a t(1;10) or variants thereof and/or ring chromosomes with possible involvement of chromosome 3. Using chromosome banding, fluorescence in situ hybridization, array-based comparative genomic hybridization, global gene expression, and real-time quantitative PCR analyses, we identified the breakpoint regions on chromosomes 1 and 10, demonstrated and delineated the commonly amplified region on chromosome 3, and assessed the consequences of these alterations for gene expression. The breakpoints in the t(1;10) mapped to TGFBR3 in 1p22 and in or near MGEA5 in 10q24, resulting in transcriptional up-regulation of NPM3 and particularly FGF8, two consecutive genes located close to MGEA5. The ring chromosomes contained a commonly amplified 1.44 Mb region in 3p11-12, which was associated with increased expression of VGLL3 and CHMP2B. The identified genetic aberrations were not confined to MIFS; an identical t(1;10) was also found in a case of HFT and the amplicon in 3p was seen in an IMFH. Copyright (c) 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
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| 8. |
- 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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| 9. |
- Zannad, F., et al.
(författare)
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Clinical outcome endpoints in heart failure trials: a European Society of Cardiology Heart Failure Association consensus document
- 2013
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Ingår i: European Journal of Heart Failure. - : Wiley. - 1388-9842 .- 1879-0844. ; 15:10, s. 1082-1094
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Tidskriftsartikel (refereegranskat)abstract
- Endpoint selection is a critically important step in clinical trial design. It poses major challenges for investigators, regulators, and study sponsors, and it also has important clinical and practical implications for physicians and patients. Clinical outcomes of interest in heart failure trials include all-cause mortality, cause-specific mortality, relevant non-fatal morbidity (e.g. all-cause and cause-specific hospitalization), composites capturing both morbidity and mortality, safety, symptoms, functional capacity, and patient-reported outcomes. Each of these endpoints has strengths and weaknesses that create controversies regarding which is most appropriate in terms of clinical importance, sensitivity, reliability, and consistency. Not surprisingly, a lack of consensus exists within the scientific community regarding the optimal endpoint(s) for both acute and chronic heart failure trials. In an effort to address these issues, the Heart Failure Association of the European Society of Cardiology (HFA-ESC) convened a group of expert heart failure clinical investigators, biostatisticians, regulators, and pharmaceutical industry scientists (Nice, France, 12-13 February 2012) to evaluate the challenges of defining heart failure endpoints in clinical trials and to develop a consensus framework. This report summarizes the group's recommendations for achieving common views on heart failure endpoints in clinical trials.
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