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EZH2 GENE UPREGULATION IN PRIMARY TESTICULAR AND CENTRAL NERVOUS SYSTEM DIFFUSE LARGE B-CELL LYMPHOMA: A POTENTIAL TARGET FOR TREATMENT IN IMMUNE-PRIVILEGED SITES?
Author(s): ,
Gabe Koenig
Affiliations:
University of Alabama at Birmingham,Birmingham,United States
,
Balabhadrapatruni V.S.K Chakravarthi
Affiliations:
University of Alabama at Birmingham,Birmingham,United States
,
Jennifer Gordetsky
Affiliations:
University of Alabama at Birmingham,Birmingham,United States
,
George Netto
Affiliations:
University of Alabama at Birmingham,Birmingham,United States
,
Maria Rodriguez-Pena
Affiliations:
University of Alabama at Birmingham,Birmingham,United States
,
Daniella Correia-Salles
Affiliations:
Johns Hopkins University,Baltimore,United States
,
Lauren Schwartz
Affiliations:
University of Pennsylvania,Philadelphia,United States
,
Julie Jorns
Affiliations:
Medical College of Wisconsin,Madison,United States
,
Sooryanarayana Varambally
Affiliations:
University of Alabama at Birmingham,Birmingham,United States
Deniz Peker
Affiliations:
University of Alabama at Birmingham,Birmingham,United States
(Abstract release date: 05/17/18) EHA Library. Peker D. 06/14/18; 216598; PB2346
Deniz Peker
Deniz Peker
Contributions
Abstract

Abstract: PB2346

Type: Publication Only

Background
Upregulation of the enhancer of zeste homolog-2 (EZH2), a histone N-methyltransferase, is a well-established in cancer development through various mechanisms. EZH2 has recently become a major target in cancer treatment. Primary central nervous system (CNS) and testicular diffuse large B-cell lymphomas (DLBCL) are rare but aggressive diseases with poor outcome due to therapeutic challenges.

Aims
In the present study, we investigated the EZH2 expression status in these two distinct variants.

Methods
A retrospective chart review, from 2003 to 2013, identified cases with a diagnosis of primary testicular and CNS DLBCL. Immunodeficiency-related, EBV-associated, and MYC gene positive LBCL were excluded from the analysis.  A formalin-fixed-paraffin-embedded tissue samples were analyzed using quantitative real-time PCR (Taqman assay) for RNA expression levels of EZH2, using custom designed primers in commercially available kits.  Control samples included three benign lymph nodes free of any neoplastic processes.

Results
Twenty-seven cases had adequate RNA extracted for analysis and PCR results were available in 18 cases; testis (n=11) and primary central nervous system (n=7). The median age was 65 years (range 41- 71 years), with a male to female ratio of 6 (M=15, F=3). Median overall survival (MOS) was 27months (2 to 74 months).

Immunophenotypic cell-of-origin subtype was determined in 15 cases using Han’s algorithm, six cases were germinal center B-cell (GCB) type (33%) and nine cases were non-GCB type (50%). Eleven cases showed higher expression of EZH2 when compared to normal lymph nodes. Five of these cases were testicular lymphoma (45%) while six cases were CNS origin (85%). The remaining seven cases did not show increased expression of EZH2.

Conclusion
Results suggest that EZH2 gene upregulation might be playing an important role, particularly in primary CNS DLBCL and possibly in testicular DLBCL; therefore might be a potential target of treatment. Larger studies are needed to establish the prognostic and therapeutic utility of RNA expression level of the EZH2 in these aggressive forms of DLBCL. 

Session topic: 19. Non-Hodgkin lymphoma Biology & Translational Research

Keyword(s): CNS lymphoma, DLBCL, EZH2

Abstract: PB2346

Type: Publication Only

Background
Upregulation of the enhancer of zeste homolog-2 (EZH2), a histone N-methyltransferase, is a well-established in cancer development through various mechanisms. EZH2 has recently become a major target in cancer treatment. Primary central nervous system (CNS) and testicular diffuse large B-cell lymphomas (DLBCL) are rare but aggressive diseases with poor outcome due to therapeutic challenges.

Aims
In the present study, we investigated the EZH2 expression status in these two distinct variants.

Methods
A retrospective chart review, from 2003 to 2013, identified cases with a diagnosis of primary testicular and CNS DLBCL. Immunodeficiency-related, EBV-associated, and MYC gene positive LBCL were excluded from the analysis.  A formalin-fixed-paraffin-embedded tissue samples were analyzed using quantitative real-time PCR (Taqman assay) for RNA expression levels of EZH2, using custom designed primers in commercially available kits.  Control samples included three benign lymph nodes free of any neoplastic processes.

Results
Twenty-seven cases had adequate RNA extracted for analysis and PCR results were available in 18 cases; testis (n=11) and primary central nervous system (n=7). The median age was 65 years (range 41- 71 years), with a male to female ratio of 6 (M=15, F=3). Median overall survival (MOS) was 27months (2 to 74 months).

Immunophenotypic cell-of-origin subtype was determined in 15 cases using Han’s algorithm, six cases were germinal center B-cell (GCB) type (33%) and nine cases were non-GCB type (50%). Eleven cases showed higher expression of EZH2 when compared to normal lymph nodes. Five of these cases were testicular lymphoma (45%) while six cases were CNS origin (85%). The remaining seven cases did not show increased expression of EZH2.

Conclusion
Results suggest that EZH2 gene upregulation might be playing an important role, particularly in primary CNS DLBCL and possibly in testicular DLBCL; therefore might be a potential target of treatment. Larger studies are needed to establish the prognostic and therapeutic utility of RNA expression level of the EZH2 in these aggressive forms of DLBCL. 

Session topic: 19. Non-Hodgkin lymphoma Biology & Translational Research

Keyword(s): CNS lymphoma, DLBCL, EZH2

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