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Prognostic Significance of Double Expression of C-MYC and BCL2 in Diffuse Large B Cell Lymphoma
Abstracts Non-Hodgkin Lymphoma
NHL-005 Prognostic Significance of Double Expression of C-MYC and BCL2 in Diffuse Large B Cell Lymphoma Hayam Rashed,1 Aziza Elsayed Abdelrahman,1 Eman Ismail,2 Ahmed Obaya ,2 Mohamed Abdelhamid3 1
Pathology Department, Faculty of Medicine, Zagazig University,
Egypt, Zagazig, Egypt; 2Clinical oncology Department, Faculty of Medicine, Zagazig University, Egypt, Zagazig, Egypt; 3General Surgery Department, Faculty of Medicine, Zagazig University, Egypt, Zagazig, Egypt
Background: Diffuse large B-cell lymphoma (DLBCL) is a heterogenous disease. Some patients of DLBCL can be cured and others relapsed after treatment. Molecular bases for different outcomes of DLBCL have been investigated but up till now many patients have been relapsed without any explanation. MYC and BCL2 co-rearrangements in DLBCL are known as double-hit lymphoma. This subtype of DLBCL is highly proliferative and therapy-resistant, with poor outcome for standard treatment. Molecular cytogenetic techniques are high expensive so we take double
expresser lymphoma diagnosed by immunohistochemistry in this study. Also number of patient relapsed are more than that diagnosed by cytogenetic as double hit lymphoma. Design: This is a retrospective study done at Zagazig university hospitals. Ninty patients diagnosed as DLBCL (from 2011 to 2015). The expressions of CMYC and BCL2 were evaluated by immunohistochemistry. MYC and BCL2 rearrangements were investigated by RT-PCR. Survival analysis was constructed from 90 (R-CHOP) treated patients. Results: C-MYC and BCL2 proteins were detected in 32% and 42% of patients, respectively. Concurrent expression (MYC positive/BCL2 positive) was present in 21% of patients. C-MYC and BCL2 mRNA were detected in 7.8% of patients (double hit). All double hit lymphoma revealed high Ki67 expression. Patient achieved OAR was 53.3%. Presence of MYC-positive/ BCL2-positive protein expression was associated with significantly poor OS and PFS. Conclusion: Double expressor lymphomas are high-grade lymphoma diagnosed by immunohistochemistry. Patients with DLBCL who co-express MYC and BCL2 proteins are high risk groups with poor OS and they can’t achieve better response to usual regimen. Intensive treatment may improve complete response rates and progression-free survival, overall survival. So we will start a clinical trial of two groups of double expressors the first will receive R-CHOP and the second group receive R-EPOCH as a first-line regimen then all cases will followed up for coming two years (20172019). Key words: Double expressor lymphoma, Immunohistochemistry, c-myc, bcl2, R-CHOP, Real Time PCR (RT-PCR).
Table 1 Crosstab Expression Non expressor BCL2 expressor Response
NR
Count
OAR
% within Expression Count
6.8% 41
64.3% 5
% within Expression Count
93.2% 44
% within Expression
100.0%
Total
3
C-MYC expressor
9
4
Double expressor
Total
26
42
80.0% 1
96.3% 1
46.7% 48
35.7% 14
20.0% 5
3.7% 27
53.3% 90
100.0%
100.0%
100.0%
100.0%
C-MYC expressor
Double expressor
Total
3
7
Table 2 Crosstab Expression Non expressor BCL2 expressor Mortality
Total
Alive
Count
Died
% within Expression Count
-
100.0%
% within Expression Count % within Expression
S360
44
44 100.0%
Clinical Lymphoma, Myeloma & Leukemia September 2017
12
66
85.7% 2
60.0% 2
25.9% 20
73.3% 24
14.3% 14
40.0% 5
74.1% 27
26.7% 90
100.0%
100.0%
100.0%
100.0%
NHL-005 Prognostic Significance of Double Expression of C-MYC and BCL2 in Diffuse Large B Cell Lymphoma Hayam Rashed,1 Aziza Elsayed Abdelrahman,1 Eman Ismail,2 Ahmed Obaya ,2 Mohamed Abdelhamid3 1
Pathology Department, Faculty of Medicine, Zagazig University,
Egypt, Zagazig, Egypt; 2Clinical oncology Department, Faculty of Medicine, Zagazig University, Egypt, Zagazig, Egypt; 3General Surgery Department, Faculty of Medicine, Zagazig University, Egypt, Zagazig, Egypt
Background: Diffuse large B-cell lymphoma (DLBCL) is a heterogenous disease. Some patients of DLBCL can be cured and others relapsed after treatment. Molecular bases for different outcomes of DLBCL have been investigated but up till now many patients have been relapsed without any explanation. MYC and BCL2 co-rearrangements in DLBCL are known as double-hit lymphoma. This subtype of DLBCL is highly proliferative and therapy-resistant, with poor outcome for standard treatment. Molecular cytogenetic techniques are high expensive so we take double
expresser lymphoma diagnosed by immunohistochemistry in this study. Also number of patient relapsed are more than that diagnosed by cytogenetic as double hit lymphoma. Design: This is a retrospective study done at Zagazig university hospitals. Ninty patients diagnosed as DLBCL (from 2011 to 2015). The expressions of CMYC and BCL2 were evaluated by immunohistochemistry. MYC and BCL2 rearrangements were investigated by RT-PCR. Survival analysis was constructed from 90 (R-CHOP) treated patients. Results: C-MYC and BCL2 proteins were detected in 32% and 42% of patients, respectively. Concurrent expression (MYC positive/BCL2 positive) was present in 21% of patients. C-MYC and BCL2 mRNA were detected in 7.8% of patients (double hit). All double hit lymphoma revealed high Ki67 expression. Patient achieved OAR was 53.3%. Presence of MYC-positive/ BCL2-positive protein expression was associated with significantly poor OS and PFS. Conclusion: Double expressor lymphomas are high-grade lymphoma diagnosed by immunohistochemistry. Patients with DLBCL who co-express MYC and BCL2 proteins are high risk groups with poor OS and they can’t achieve better response to usual regimen. Intensive treatment may improve complete response rates and progression-free survival, overall survival. So we will start a clinical trial of two groups of double expressors the first will receive R-CHOP and the second group receive R-EPOCH as a first-line regimen then all cases will followed up for coming two years (20172019). Key words: Double expressor lymphoma, Immunohistochemistry, c-myc, bcl2, R-CHOP, Real Time PCR (RT-PCR).
Table 1 Crosstab Expression Non expressor BCL2 expressor Response
NR
Count
OAR
% within Expression Count
6.8% 41
64.3% 5
% within Expression Count
93.2% 44
% within Expression
100.0%
Total
3
C-MYC expressor
9
4
Double expressor
Total
26
42
80.0% 1
96.3% 1
46.7% 48
35.7% 14
20.0% 5
3.7% 27
53.3% 90
100.0%
100.0%
100.0%
100.0%
C-MYC expressor
Double expressor
Total
3
7
Table 2 Crosstab Expression Non expressor BCL2 expressor Mortality
Total
Alive
Count
Died
% within Expression Count
-
100.0%
% within Expression Count % within Expression
S360
44
44 100.0%
Clinical Lymphoma, Myeloma & Leukemia September 2017
12
66
85.7% 2
60.0% 2
25.9% 20
73.3% 24
14.3% 14
40.0% 5
74.1% 27
26.7% 90
100.0%
100.0%
100.0%
100.0%