Immunoglobulin heavy-chain gene rearrangement in B-cell non- Hodgkin lymphoma using the fluorescence in-situ hybridization technique

Objectives Non-Hodgkin lymphoma (NHL) comprises an extremely heterogeneous group of clonal lymphoproliferative disorders that might be derived from either B-cell or T/NK-cell lineages. The molecular pathogenesis of NHL represents a complex process involving the accumulation of multiple genetic lesions, which include the activation of proto-oncogens such as BCL-1, BCL2, BCL6, and c-MYC by chromosomal translocation, as well as inactivation of tumor-suppressor genes such as TP53 by chromosomal deletion or mutation. Aim of the study The present study aimed to detect immunoglobulin heavy-chain (IgH) gene rearrangement by the fluorescent in-situ hybridization (FISH) technique in paraffin-embedded bone marrow trephine and lymph node biopsies, and to correlate the presence of IgH chain gene rearrangement to the standard prognostic factors of NHL. Participants and methods The present study was carried out on 50 newly diagnosed adults with NHL. The study included 26 diffuse large B-cell lymphoma patients, 21 follicular lymphoma (FL) patients, and three mantle cell lymphoma patients. FISH was performed using LSI 14q break-apart rearrangement probes. Results The IgH gene rearrangement was detected by the FISH technique in lymph node sections of 36 out of 50 patients (72%) and only in six patients (12%) by trephine biopsy; also, it was found that 14q+ve patients were significantly associated with advanced stage of disease as well as low hemoglobin level, high total leukocytic count, low platelet count, high peripheral blood lymphocyte percentage, high lactate dehydrogenase level, and a high International Prognostic Index score. For diffuse large B-cell lymphoma, IgH gene rearrangement was detected in lymph node sections of 17/26 (65.4%) patients and in two patients by trephine biopsy, indicating a highly significant difference. In FL patients, IgH gene rearrangement was detected by the FISH technique in lymph node sections in 16/21 (76%) patients and in one patient (5%) by trephine biopsy, with a high statistical significance. For mantle cell lymphoma, IgH gene rearrangement was detected in all patients 3/3 (100%) both by lymph node and by trephine biopsies. Conclusion This study shows the increasing importance of detailed cytogenetic analysis of NHL cases and focuses on the necessity of use of the FISH technique on lymph node as it identifies early cytogenetic aberrations that are not detected in a bone marrow trephine biopsy, except in stage IV lymphoma.