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排序方式: 共有815条查询结果,搜索用时 15 毫秒
811.
Dagmar Berghuis Alfons SK de Hooge Susy J Santos Danielle Horst Emmanuel J Wiertz Marja C van Eggermond Peter J van den Elsen Antonie HM Taminiau Laura Ottaviano Karl‐Ludwig Schaefer Uta Dirksen Erik Hooijberg Arend Mulder Cornelis JM Melief R Maarten Egeler Marco W Schilham Ekaterina S Jordanova Pancras CW Hogendoorn Arjan C Lankester 《The Journal of pathology》2009,218(2):222-231
Ewing sarcoma (EWS) is a tumour most commonly arising in bone, although on occasion in soft tissue, with a poor prognosis in patients with refractory or relapsed disease, despite multimodal therapy. Immunotherapeutic strategies based on tumour‐reactive T and/or natural killer cells may improve the treatment of advanced‐stage EWS. Since cellular immune recognition critically depends on human leukocyte antigen (HLA) expression, knowledge about HLA expression in EWS is crucial in the design of cellular immunotherapeutic strategies. Constitutive and IFNγ‐induced HLA class I expression was analysed in EWS cell lines (n = 6) by flow cytometry, using antibodies against both monomorphic and allele‐specific antigens. Expression of antigen processing pathway components and beta‐2 microglobulin (β2m) was assessed by western blot. Expression of class II transactivator (CIITA), and its contribution to HLA class II expression, was evaluated by qRT‐PCR, transduction assays, and flow cytometry. β2m/HLA class I and class II expression was validated in EWS tumours (n = 67) by immunofluorescence. Complete or partial absence of HLA class I expression was observed in 79% of EWS tumours. Lung metastases consistently lacked HLA class I and sequential tumours demonstrated a tendency towards decreased expression upon disease progression. Together with absent or low constitutive expression levels of specific HLA class I loci and alleles, and differential induction of identical alleles by IFNγ in different cell lines, these results may reflect the existence of an immune escape mechanism. Inducible expression of TAP‐1/‐2, tapasin, LMP‐2/‐7, and the β2m/HLA class I complex by IFNγ suggests that regulatory mechanisms are mainly responsible for heterogeneity in constitutive class I expression. EWSs lack IFNγ‐inducible HLA class II, due to lack of functional CIITA. The majority of EWS tumours, particularly if advanced‐stage, exhibit complete or partial absence of both classes of HLA. This knowledge will be instrumental in the design of cellular immunotherapeutic strategies for advanced‐stage EWS. Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. 相似文献
812.
Szuhai K Knijnenburg J Ijszenga M Tanke HJ Baatenburg de Jong RJ Bas Douwes Dekker P Rosenberg C Hogendoorn PC 《Cancer Genetics and Cytogenetics》2004,153(1):48-52
Approximately 10% of all mesenchymal malignancies are classified as synovial sarcomas, which show a balanced translocation t(X;18)(p11.2;q11.2) at the cytogenetic level. The occurrence of this neoplasm in the head and neck region is rare, and its lowest frequency is found in the larynx. When synovial sarcomas are present in such unusual locations, diagnosis based solely on histologic features might be problematic, and to our knowledge, cytogenetic data have been reported so far in only one case of synovial sarcoma of the larynx. Because of the rarity and shortage of consistent prognostic markers, there is no clear consensus for the treatment of these patients. Cytogenetic analysis of a primary case of synovial sarcoma of the larynx was performed by using a 48-color fluorescence in situ hybridization technique that allows differential staining of short and long chromosome arms to establish the karyotype. We report here the molecular cytogenetic analyses of a synovial sarcoma of the larynx harboring the diagnostic t(X;18), as well as trisomies 2 and 8. The karyotypic information on synovial sarcomas of the larynx is scarce, and our data might add to the diagnosis and prognosis of this tumor. 相似文献
813.
de Andrea CE Kroon HM Wolterbeek R Romeo S Rosenberg AE De Young BR Liegl B Inwards CY Hauben E McCarthy EF Idoate M Athanasou NA Jones KB Hogendoorn PC Bovée JV 《Modern pathology》2012,25(9):1275-1283
The distinction between benign and malignant cartilaginous tumors located peripherally in the bone may be a challenging task in surgical pathology. The aim of this study was to investigate interobserver reliability in histological diagnosis of cartilaginous tumors in the setting of multiple osteochondromas and to evaluate possible histological parameters that could differentiate among osteochondroma, low- and high-grade secondary peripheral chondrosarcoma. Interobserver reliability was assessed by 12 specialized bone-tumor pathologists in a set of 38 cases. Substantial agreement on diagnosis among all the reviewers was observed (intraclass correlation coefficient=0.78). Our study confirmed that mitotic figures and nuclear pleomorphism are hallmarks of high-grade secondary peripheral chondrosarcoma. However, despite the substantial agreement, we demonstrated that histology alone cannot distinguish osteochondroma from low-grade secondary peripheral chondrosarcoma in the setting of multiple osteochondromas, as nodularity, the presence of binucleated cells, irregular calcification, cystic/mucoid changes and necrosis were not helpful to indicate malignant transformation of an osteochondroma. On the other hand, among the concordant cases, the cartilage cap in osteochondroma was significantly less thicker than in low- and high-grade secondary peripheral chondrosarcoma. Therefore, our study showed that a multidisciplinary approach integrating clinical and radiographical features and the size of the cartilaginous cap in combination with a histological assessment are crucial to the diagnosis of cartilaginous tumors. 相似文献
814.
815.
Hameetman L Kok P Eilers PH Cleton-Jansen AM Hogendoorn PC Bovée JV 《Virchows Archiv : an international journal of pathology》2005,446(4):430-437
Distinguishing osteochondroma from low-grade secondary peripheral chondrosarcoma can be difficult. In osteochondroma, growth-signalling pathways are thought to be downregulated through exostosin (EXT) inactivation. A previous pilot study focusing on expression of putative EXT downstream effectors indicated that progression of osteochondroma towards grade I chondrosarcoma was characterised by upregulation of Bcl-2 and parathyroid hormone-like hormone (PTHLH). We investigated their use as diagnostic markers in a large nationwide series of 71 osteochondromas and 34 chondrosarcomas. Bcl-2 immunohistochemistry proved to be a valuable diagnostic tool: scoring negative in 95% (specificity) of the osteochondromas and positive in 57% (sensitivity) of the chondrosarcomas, reaching a positive predictive value of 84% and negative predictive value of 82%. Positivity was not related to age, hereditary status, gender or thickness of the cartilage cap. Presence of internal controls and verification using mRNA in situ hybridisation strengthened the reliability of the immunohistochemical staining. PTHLH showed more variable staining, being positive in osteochondromas from females or adolescent males, suggesting age- and gender-dependent expression. Thus, in cases where the distinction between osteochondroma and chondrosarcoma is difficult, Bcl-2 is a valuable diagnostic marker for malignancy, regardless of tumour size, patient gender or age, and this can be extended with PTHLH for non-adolescent male patients. 相似文献