Abstract

BackgroundDiffuse Large B-Cell Lymphoma is the most common type of Non-Hodgkin Lymphoma. Genetic studies have revealed that one of its molecular subtypes resistant to treatment by standard protocols occurs when there are concurrent translocations in the C-MYC and BCL2 or BCL6 genes constituting the type known as double hit lymphoma (DHL). Double expresser lymphoma (DEL) is another subtype that is much more frequent, including about 20-30% of cases. It occurs when there is protein overexpression of C-MYC together with BCL2 or BCL6 proteins without actual gene translocation. MethodsTissue microarray platform was constructed using cores from selected areas of each specimen. Hematoxylin and Eosin slides were reviewed for confirmation of pathologic diagnosis and immunohistochemistry was used for detection of C-MYC, BCL2 and BCL6 expression. Stained slides were assessed for percentage of cellular expression for each marker where median expression was used as the threshold value for defining positivity. DLBCL with high expression for MYC and BCL2 or BCL6 was defined as DEL. ResultsTissue microarray blocks were constructed from the paraffin blocks of 87 cases with a confirmed diagnosis of DLBCL. Median age for participants was 58 years. CMYC, BCL2, and BCL6 showed high protein expression in 50.6% (n=44), 55.2% (n=48), and 54% (n=47) respectively. Cases with DEL constituted 44.8% of sample (n=39), where DEL was significantly higher in patients with poor performance status (PS>1). Neither of the associations between DEL and other patients’ or disease’s characteristics (age, gender, smoking history, family history, comorbidities, B symptoms, LDH, B2 microglobulin, stage, BM infiltration, presence of more than one extranodal site, IPI, and risk group) tested positive. There were no associations between DEL and response, PFS, DFS, or OS. ConclusionsDEL is not uncommon among studied sample constituting around 44.8% of cases. This positive protein expression was commonly found in patients with poor performance status creating a particular therapeutic challenge. DEL did not correlate with other variables including known prognostic factors for DLBCL. DEL did not also show effect on further treatment outcomes including response and survival. Legal entity responsible for the studyThe authors. FundingHas not received any funding. DisclosureAll authors have declared no conflicts of interest.

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