DLBCL

Clinical and Prognostic Value of Molecular Markers of Diffuse Large B-Cell Lymphoma

REVIEWS , , , , , ,

SM Rastorguev1, DA Koroleva2, ES Boulygina1, SV Tsygankova1, NG Goncharov1, OS Naraikin1, NG Gabeeva2, EE Zvonkov2, AV Nedoluzhko1

1 National Research Center “Kurchatov Institute”, 1 Akademika Kurchatova sq., Moscow, Russian Federation, 123182

2 National Medical Hematology Research Center, 4а Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167

For correspondence: Artem Valer’evich Nedoluzhko, PhD in Biology, 1 Akademika Kurchatova sq., Moscow, Russian Federation, 123182; Tel.: +7(916)670-55-95; e-mail: nedoluzhko@gmail.com

For citation: Rastorguev SM, Koroleva DA, Bulygina ES, et al. Clinical and Prognostic Value of Molecular Markers of Diffuse Large B-Cell Lymphoma. Clinical oncohematology. 2019:12(1):95–100.

DOI: 10.21320/2500-2139-2019-12-1-95-100

ABSTRACT

Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoid tumor in adults which is associated with approximately 30–40 % of all non-Hodgkin’s lymphomas. Diagnostic criteria include diffuse growth of large anaplastic tumor cells, expression of В-cell markers, and a high proliferative index. Due to the development of molecular genetic technologies it became obvious that underlying cause of clinical diversity is a huge amount of genetic failures which determine epigenetic modification of gene expression, activation variability of certain signaling pathways, and immunological properties of tumor cells. The study and systemization of molecular markers present a significant trend in DLBCL diagnosis and treatment. This review discusses most important molecular markers and current view on their clinical value.

Keywords: lymphoma, DLBCL, B-cells, transcriptomics, gene expression, epigenomics, genomics.

Received: July 3, 2018

Accepted: December 10, 2018

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Prognostic and Differential Diagnostic Value of Standardized Uptake Volume (SUV) of Fluorodeoxyglucose in Patients with Hodgkin’s Lymphoma

LYMPHOID TUMORS , ,

AA Rukavitsyn, SI Kurbanov, OA Rukavitsyn

Academician NN Burdenko Principal Military Clinical Hospital under the Ministry of Defence of the Russian Federation, 3 Gospital’naya pl., Moscow, Russian Federation, 105229

For correspondence: Anatolii Anatol’evich Rukavitsyn, 3 Gospital’naya pl., Moscow, Russian Federation, 105229; Tel: +7(499)263-53-17; e-mail: rukavitsin46@gmail.com

For citation: Rukavitsyn AA, Kurbanov SI, Rukavitsyn OA. Prognostic and Differential Diagnostic Value of Standardized Uptake Volume (SUV) of Fluorodeoxyglucose in Patients with Hodgkin’s Lymphoma. Clinical oncohematology. 2017;10(2):182–6 (In Russ).

DOI: 10.21320/2500-2139-2017-10-2-182-186

ABSTRACT

Background & Aims. Hodgkin’s lymphoma (HL) is still considered one of the most curable oncohematological diseases of lymphoid tissue. 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) combined with multispiral computed tomography (CT) is one of precise and easily available methods of imaging of lymphoid neoplasia. The aim is to determine the correlation between the standardized uptake volume (SUV) of 18F-FDG and results of the first-line anti-tumor treatment of HL patients; to evaluate the possibility of differential diagnosis between HL and diffuse large B-cell lymphomas (DLBCL) based on SUV.

Materials & Methods. 76 patients (69 men and 7 women) aged from 19 to 75 years (median age 36.7 years) with DLBCL (n = 22) and HL (n = 54) were retrospectively enrolled in the study. The diseases were diagnosed over the period from 2011 until 2015. A combined PET-CT imaging was performed for the disease staging.

Results. The comparison of median SUVs in patients with HL (n = 54) and DLBCL (n = 22) demonstrated that the difference had a very high level of significance (p < 0.001). HL patients demonstrated a significantly lower 18F-FDG SUV than DLBCL patients. The analysis of PET findings demonstrated a correlation between the chosen treatment option for the lymphoma and the SUV level (p < 0.001). HL patients demonstrated an insignificant negative correlation between the SUV level rise and the treatment outcome (p = 0.2).

Conclusion. The SUV level does not affect the treatment outcomes of HL patients according to the ABVD protocol, as well as the metabolic response rate and tumor mass reduction. However, the SUV levels significantly differ in patients with HL and DLBCL. These data may be used as additional criteria for differential diagnosis of HL and DLBCL.

Keywords: SUV, PET-CT, Hodgkin’s lymphoma, DLBCL.

Received: November 21, 2016

Accepted: January 23, 2017

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MYC and BCL2 Protein Expression in Patients with Diffuse Large B-cell Lymphoma

LYMPHOID TUMORS , , , ,

AE Misyurina1, AM Kovrigina1, EA Baryakh1, VA Misyurin2, SK Kravchenko1, AV Misyurin2, TN Obukhova1, SM Kulikov1, AN Kopylov2, AU Magomedova1, EG Gemdzhyan1, AI Vorob’ev1

1 Hematology Research Center under the Ministry of Health of the Russian Federation, 4а Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167

2 N.N. Blokhin Russian Cancer Research Center, 24 Kashirskoye sh., Moscow, Russian Federation, 115478

For correspondence: Anna Evgen’evna Misyurina, 4а Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167; Tel.: +7(909)637-32-46; e-mail: anna.lukina1@gmail.com

For citation: Misyurina AE, Kovrigina AM, Baryakh EA, et al. MYC and BCL2 Protein Expression in Patients with Diffuse Large B-cell Lymphoma. Clinical oncohematology. 2015;8(1):44–53 (In Russ).

ABSTRACT

Objective. The objective of this study is to analyze the incidence and the role of MYC and BCL2 protein expression in patients with diffuse large B-cell lymphoma (DLBCL) and to compare data of histological, immunohistochemical, genetic, and moleculobiological analyses with clinical characteristics.

Methods. 62 patients with confirmed diffuse large B-cell lymphoma (DLBCL) were enrolled in the study; they underwent treatment according to the original modified protocol NHL-BFM-90 ± R in the Hematology Research Center under the Ministry of Health of the Russian Federation. A reference group consisted of 13 DLBCL patients who underwent СНОР-like ± R therapy. In all observations, histological and immunohistochemical tests were performed in archived biopsy samples of a tumor tissue or a lymph node (paraffin blocks) using BCL2 (clone 124, Dako) and MYC antibodies (clone Y69, Epitomics). Based on C.P. Hans’s algorithm (2004), GCB and non-GCB immunohistochemical subtypes of DLBCL were determined. Standard cytogenetic tests (n = 22) and FISH analysis (n = 52) were performed in this study in order to determine locus translocation of с-MYC gene, IgH gene, t(8;14)(q24;q32), BCL2 gene, t(14;18)(q32;q21). Quantitative RT-PCR on paraffin tumor/node biopsy samples was also performed to evaluate the number of mRNAs of с-MYC and BCL2 genes.

Results. MYC expression was found in 24 (39 %) of 62 DLBCL patients and BCL2 in 36 (58 %) of 62 patients (threshold values were 40 % and 50 % of tumor cells, respectively). MYC/BCL2 coexpression was diagnosed in 15 (24 %) of 62 DLBCL patients. 4 (27 %) of 15 patients with MYC/BCL2 coexpression had a GCB-subtype of DLBCL, 73 % patients with MYC/BCL2 coexpression were diagnosed with non-GCB subtype of DLBCL (p < 0.02). c-MYC rearrangement was found in two cases (3 %), one of them had a MYC protein expression score more than 40 %. 10 (19 %) patients had one or more additional signal from 8q24 locus of c-MYC gene. We didn’t find any correlation between the presence of additional signals from c-MYC gene locus and the level of immunohistochemical expression of MYC protein ³ 40 % (p < 0.05). BCL2 gene rearrangement was detected in one case; it was accompanied by BCL2 protein immunohistochemical expression ³ 50 %. BCL2 amplification was observed in 17 (40 %) patients. There was a correlation between the amplification of BCL2 gene and immunohistochemical expression of BCL2 protein (threshold value was ³ 50 % of positive cells) (p = 0.0053). There was a direct correlation between the amount of mRNAs and MYC protein (correlation coefficient 0.86; p < 0.0001). There was no correlation between the level of BCL2 gene expression and the amount of protein (correlation coefficient 0.14; p = 0.57). Four-year overall survival for DLBCL patients treated with m-NHL-BFM-90 ± R was 71 % (in patients without MYC/BCL2 coexpression) vs 57 % (in patients with MYC/BCL2 coexpression) (p = 0.39). The probability of relapse or progression of DLBCL was significantly higher in patients with MYC/BCL2 coexpression, than in patients without MYC/BCL2 coexpression (65 % vs 15 %; p = 0.0029).

Conclusions. The MYC/BCL2 coexpression is observed mainly in DLBCL patients with non-GCB immunohistochemical subtype of the disease. The MYC/BCL2 coexpression is vital for prediction of the risk of relapses/progression of the disease in patients receiving an intensive chemotherapy according to the m-NHL-BFM-90 ± R protocol. Taking into account a relatively stable structure of the protein substrate, the obtained data may become a basis for development of a diagnostic immunohistochemical algorithm for stratification of DLBCL patients.

Keywords: DLBCL, intensive therapy, MYC/BCL2 coexpression, immunohistochemistry, unfavorable prognostic factor.

Received: November 8, 2014

Accepted: November 11, 2014

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