Das Mikroenvironment des Follikulären Lymphoms zum Zeitpunkt der Primärdiagnose und des Rezidivs

Introduction: Follicular lymphoma (FL) presents the second common non-Hodgkin lymphoma in the western world. FL histological imitate the growth pattern and the cytology of reactive follicles. The translocation t(14;18) is characteristic. The translocation juxtaposes the anti-apoptotic protein BCL2 and the high expressed immunoglobulin heavy-chain gene in B-cells, thus it leads to an overexpression of BCL2- genes. The translocation is not sufficient to develop a FL, other secondary genetic hits are necessary to transform a t(14;18)-positive B-cell into a neoplastic cell. The clinical course is mostly indolent, except the cases of FL that experience a histological transformation to diffuse large B-cell lymphoma, which leads to a poorer prognosis. Within the tumor FL shows numerous non-neoplastic bystander cells. This so-called microenvironment is associated with the prognosis in its composition. A composition with predominant macrophages is associated with a favorable prognosis, whereas a dominance of dendritic cells is associated with an unfavorable prognosis. These results are still controversial. In previous studies the research group showed that the composition of the microenvironment correlates with the stage of disease at the point of diagnosis. In this study we research if changes in the microenvironment of FL are detectable during the course of the disease. We especially examine whether there is a transformation of the microenvironment from a physiological imitating microenvironment to a neoplastic specific microenvironment. Methods/Material: Sequential biopsies from patients were accessed, by examining the tissue at the primary diagnosis and the relapse. Therefore Immunohistochemical staining and analysis were performed on formalin fixed and paraffin-embedded samples from 20 patients who we identified in the files of the Lymph Node Regisrty. Immunohistochemical staining was done for specific compartments of the microenvironment e.g. Forkhead Box Protein 3 (FoxP3) and Programmed Death-1 (PD-1) to detect regulatory T-cells or follicular T-helper cells. Manual counting or digital image analysis assessed the content of positively stained cells. Furthermore by the means of NanoString digital gene expression the FL microenvironment will be analysed. The RNA was isolated with the ExpressArt FFPE Clear RNA ready kit from AmpTec. Results: Comparing primary diagnosis and relapses the Immunohistochemical analysis yielded no change in the composition of the microenvironment. Rudimentary two tendencies could be assumed, but it was not yet possible to state these tendencies precisely as the cohort is too small. The Validation of the NanoString/nCounter Technologies is currently ongoing. First results show no striking difference between primary diagnoses and relapse gene expressions. Conclusion: To strengthen our assumption the cohort got enlarged and the validation is ongoing.


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