Foliküler Lenfomaların ve Yeni Tanımlanmış Bcl2 Negatif Alt Grubunun Epha7, Ezh2 Ekspresyonu ve Bcl2 Break-Apart Açısından Analizi, Sonuçlarının Karşılaştırılması ve Histopatolojik Korelasyonu

Abstract

Follicular lymphoma (FL) is a mature B cell lymphoma thougt to arise from germinal center B cells and is the second most common subtype of non-Hodgkin lymphoma (NHL). Cure of FL is a significant problem and in fact it is thought to be incurable with standart chemotherapy modality. The recently identified genetic lesion of FL, constitute potential new therapies against FL. The aim of this study to examine the immunohistochemical expression of BCL2, EZH2 and EPHA7 and define this BCL2 negative subgroup among our follicular lymphoma cases. In the scope of this study, 102 biopsy specimens from 98 patients diagnosed as FL in Hacettepe University Department of Pathology in 2000 – 2014, were re-evaluated. 28,4% of the cases were grade 1 FL, 39,2% were grade 2 FL and 32,4% were grade 1-2 FL. The clinical and demographic data of patients were obtained from our patients' database. The immunohistochemical study was performed on representative blocks of tissues for BCL2 clone 100/D5, BCL2 clone E17, BCL2 clone SP66, EZH2 ve EPHA7 expression levels. Later, tissue microarrays were prepared, containing tumor tissue samples of 40 cases which were seen to be negative or partially positive with either of the 3 BCL2 clones used. BCL2 break-apart was investigated by in-situ hybridization on sections from the microarray. It was seen that patients with bone marrow involvement had a better prognosis than those without bone marrow involvement. BCL2 positivity was seen to differ with respect to the BCL2 clone used (clone 100/D5 21,6%, clone E17 14,7% and clone SP66 8,8%). BCL2 clone SP66 turned out to be the one with least negative results and least affected by poor fixation. None of the 27 cases in which FISH analysis gave results demonstrated breaks or amplification in BCL2. This could a result of lower frequency of BCL2 translocation in our case group than in those of Western population. EZH2 was found to be positive in 91.2% of the cases (93/102 cases) and EPHA7 loss was detected in 14.7% of the cases (15/101 cases). %80 of centrocytes and %40 of centroblasts in germinal centers are found to be nuclear positive with EZH2 (This rate is higher than expected Ki-67 levels in germinal centers). We thus came to the conclusion that immunohistochemistry of BCL2, EZH2 and EPHA7 may have a role in the future in directing targeted therapy of FL.