Higher Expression of CD44 in De Novo Diffuse Large B-cell Lymphoma Than in Richter Syndrome: USCAP 2022 Abstracts: Hematopathology (851-976)

Background: A subset of patients with chronic lymphocytic leukemia will experience transformation into Richter syndrome (RS), usually a diffuse large B–cell lymphoma (DLBCL). Clonal relationship based on IGHV analysis can determine a true RStransformation. Separating de novo DLBCL and RS is essential because novo DLBCL have a significantly better prognosis. The aim of this study is to find differentially expressed proteins in RS and de novo DLBCL.Design: The study comprised a total of 44 samples, specifically 18 RS and 26 de novo DLBCL of the non-GCB type. Among the RS, 8 were clonally related, 2 were clonally unrelated and for 8 no information was available regarding the clonal relationship. Initial proteomic screening analysis was processed through liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). Among this 44 samples, 20 (10 RS and 10 de novo DLBCL) were analyzed by immunohistochemistry in order to evaluate the expression of CD44 and PKC-β. H-score was calculated with the semi quantitative evaluation of percentage of positive PKC-β cells multiplied by the weighted intensity of stain. All statistical analyses were performed using Student’s t-test. A p < 0.05 was considered statistically significant.Results: LC-MS/MS proteomic study identified a panel of proteins differentially expressed between RS and de novo DLBCLs (FDR<0.05), including CD44 (which was comparatively underexpressed in RS) and PKC-β (which was comparatively overexpressed in RS). The immunohistochemical study confirmed that CD44 expression is significantly higher in de novo DLBCL than in RS (p<0.002). PKC-β is also overexpressed in RS, but the difference is not significant.Conclusions: RS has a very poor prognosis and should not be confused with de novo DLBCL. This study demonstrated the interest of CD44 to immunophenotically distinguish RS from de novo DLBCL

Large-Scale Proteomics Identifies Distinct Signatures for Richter Syndrome and De Novo Diffuse Large B-Cell Lymphoma: A French Study from the Filo Group

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