Genexpressionsanalyse der Zusammensetzung des Microenvironments im klassischen Hodgkin- Lymphom bei Erstdiagnose und im Rezidiv

Classical Hodgkin lymphoma is dominated by the nonneoplastic microenvironment, while the neoplastic Hodgkin-Reed-Sternberg cells compose only a minority of cells in the lymphoma tissue. The histological subtypes of classical Hodgkin lymphoma are defined based on the composition of the nonneoplastic microenvironment. Furthermore, gene expression profiling studies have suggested that the microenvironment at diagnosis might be associated with the clinical course of the disease. In this study we analyzed sequential biopsy specimens obtained at diagnosis and at relapse from the same patient for morphology, immunophenotype and gene expression profiling using formalin-fixed paraffin-embedded tissue and Nanostring/nCounter technology. The morphological subtype changed between primary and relapse biopsy in 20% of cases. The immunophenotype was stable with respect to CD30, CD3 and LMP1 but variable with respect to CD15 and CD20 expression. Gene expression revealed 8 up- and 20 down-regulated genes at relapse (p≤0.05) with a consistent logarithmic fold change direction in at least 75% of all cases. We found discrepancies between gene expression suggestive of cell types and number of cells assessed by immunohistochemistry. Our data illustrate microenvironmental dynamics over the cause of the disease and emphasize the importance of correlating gene expression with cell counts to draw a clear picture of the microenvironment in Hodgkin Lymphoma.


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