<> "The repository administrator has not yet configured an RDF license."^^ . <> . . "Immunohistochemical analysis of potentially targetable markers in histiocytic disorders"^^ . "Histiocytosis describes a heterogenous group of rare disorders of the mononuclear phagocyte system.\r\nThese disorders can clinically present in any organ with varying severity and age of onset. They can\r\nmanifest in form of a single self-healing lesion or as a severe therapy-resistant disseminated disease.\r\nSuch systemic forms often require salvage therapy when first- and second-line treatment fail.\r\nRecently, targeted therapy with BRAF inhibitors can be used for patients with verified BRAF\r\nmutations. The aim of this study is to find more targetable markers that increase the range of possible\r\ntreatment for patients with Langerhans cell histiocytosis (LCH) and non-Langerhans cell histiocytosis\r\n(NLCH) by analysing druggable key signalling pathways and molecules. The analysed parameters\r\nwere mitogen-activated protein kinase (MAPK) pathway components, proteins of the neurotrophic\r\ntyrosine receptor kinase (NTRK) family and immunorelevant programmed cell death-ligand 1 (PD-L1).\r\nClinicohistopathological and tissue microarray (TMA) data from 69 patients with a diagnosed form of\r\nhistiocytosis were acquired and evaluated within the scope of a multicentric and retrospective study.\r\nData and tissue samples of patients with LCH, xanthogranuloma (XG), necrobiotic xanthogranuloma\r\n(NXG), xanthoma disseminatum (XD), Rosai-Dorfman disease (RDD), Erdheim-Chester disease\r\n(ECD) and generalized eruptive histiocytosis (GEH) were collected. Only tissue samples with\r\nhistopathologically confirmed diagnoses were utilized, further validated through specific\r\nimmunohistochemical (IHC) stainings against diagnostic markers after generating TMAs. XG and LCH\r\nwere each grouped in high- and low-risk subtypes. They were evaluated using a semiquantitative\r\nmultiplicative quickscore method (IHC score), which considers staining intensity and the percentage of\r\nimmunopositive cells, in order to identify potential therapeutical targets and correlations with\r\nclinicohistopathological data. Antibodies of significant value were the following: anti-PD-L1, anti-ERK2,\r\nanti-MEK2, anti-pMEK1/2, anti-MEK1/2 and anti-ERK1/2.\r\nThis study appears to be the first to detect significant PD-L1 overexpression in XG, especially in\r\ndisseminated XG. It implies the involvement of PD-L1 in XG pathobiology and indicates a potential\r\nrole of XG cells in immune evasion and tumour progression. Patients with higher levels of PD-L1\r\nexpression are likely to benefit from therapy with immune checkpoint inhibitors (PD-1/PD-L1-blockade\r\ntherapy). Further results confirm the known association between MAPK pathway proteins and\r\nhistiocytoses. Firstly, there were findings of significant MEK overexpression in high-risk LCH and XG.\r\nHigh MEK expression can be synonymous with a possible MEK mutation and can (over)activate\r\nERK1/2. The use of MEK inhibitors in MEK-positive LCH and NLCH without BRAF overexpression or\r\nin severe LCH and NLCH cases can be suggested in order to improve clinical outcome. Secondly, the\r\nanalysis of ERK undertaken here showed a significant ERK overexpression in multifocal and\r\nmultisystemic LCH and in XG. This is most likely due to an (over)activation of upstream MAPK\r\npathway components. These results indicate that histiocytosis cases with ERK overexpression might\r\nprofit from treatment with ERK inhibitors in the future, although these are not yet clinically established.\r\nTaken together, this work represents a significant step forward in understanding histiocytic disorders\r\nand identifying potentially targetable markers for LCH and NLCH patients."^^ . "2024" . . . . . . . "Love-Elizabeth"^^ . "Odita"^^ . "Love-Elizabeth Odita"^^ . . . . . . "Immunohistochemical analysis of potentially targetable markers in histiocytic disorders (PDF)"^^ . . . "Dissertation_Odita_Love-Elizabeth (finale Version).pdf"^^ . . . "Immunohistochemical analysis of potentially targetable markers in histiocytic disorders (Other)"^^ . . . . . . "lightbox.jpg"^^ . . . "Immunohistochemical analysis of potentially targetable markers in histiocytic disorders (Other)"^^ . . . . . . "preview.jpg"^^ . . . "Immunohistochemical analysis of potentially targetable markers in histiocytic disorders (Other)"^^ . . . . . . "medium.jpg"^^ . . . "Immunohistochemical analysis of potentially targetable markers in histiocytic disorders (Other)"^^ . . . . . . "small.jpg"^^ . . . "Immunohistochemical analysis of potentially targetable markers in histiocytic disorders (Other)"^^ . . . . . . "indexcodes.txt"^^ . . "HTML Summary of #34915 \n\nImmunohistochemical analysis of potentially targetable markers in histiocytic disorders\n\n" . "text/html" . . . "610 Medizin"@de . "610 Medical sciences Medicine"@en . .