PROGNOSTIC IMPACT OF MYC/BCL-2 PROTEIN OVEREXPRESSION IN DIFFUSE LARGE B-CELL LYMPHOMA (DLBCL) IN THE RITUXIMAB ERA: A SINGLE-INSTITUTION EXPERIENCE.
(Abstract release date: 05/19/16)
EHA Library. García-Sanchis L. 06/09/16; 134608; PB1708
Dr. Laura García-Sanchis
Contributions
Contributions
Abstract
Abstract: PB1708
Type: Publication Only
Background
.Protein overexpression and rearrangements of myc and bcl-2 genes have been related with an adverse prognosis in diffuse large B-cell lymphoma (DLBCL) patients in the rituximab era. But data are not always consistent and sometimes contradictory.
Aims
to analyze the incidence of MYC and BCL2 protein overexpression in DLBCL as well as to evaluate the prognostic impact in terms of time to progression (TTP) and overall survival (OS).
Methods
We carried out a single institution study with tissue biopsies obtained from patients diagnosed of DLBCL in the period 1994-2011. Tissue fixation and processing were performed using standard methods. Tissue microarrays (TMAs) that contained two representative 2-mm cores from each tumor were prepared. Immunohistochemical stainnings were performed using fully automated protocols. We used the following antibodies: MYC (clone Y69;Roche), BCL2 (clone 124; DAKO). The cut-off level for BCL2 and MYC expression was 50% and 10% respectively. MYC and BCL2 expression were evaluated by an pathologist expert as well as an hematologist. At the same time, MYC and BCL2 expression was evaluated using computerized image analysis with Image Pro Plus 6.0. A mean number of 1000 cells were analyzed per case. TTP and OS curves were built by the Kaplan_Meier method and compared by the log-rank test. Impact of TTP and OS was studied by the Cox regression test. Results: 140 DLBCL patients were included, median age was 70 (23-76), male/female ratio 73/67, Ann Arbor stage III or IV: 73 (52%), high LDH 72 (51%), high β2-microglobulin 62 (44%) low risk IPI 53 pt, int-low 26pt (19%), int-high 31pt (23%), high 28pt (20%) IPI ≥ 3: 59pt (42.1%). 45 patient were treated with CHOP-like regimens and 95 with rituximab-CHOP schedules. Median follow-up (alive pts) was 49 months(12,135).
Results
We observed MYC overexpression (≥10%) in 101pt (72%), BCL2 overexpression (≥50%) in 71pt (50%) and both in 56pt (40%). We did not observe any correlationship between MYC, BCL2 or both overexpression and clinical-biologic baseline characteristics. Patients with MYC and BCL2 overexpression had a lower complete response rate than the rest: 62% versus 76% (p=0.09). Patients with both markers had a worse 5 year TTP: 67% versus 83% (p0.09) and also a worse 5 year OS: 60% versus 79% (p0.05),. When we restricted the analysis to the rituximab-treated patients, patients with both markers had a worse 5-y TTP and OS than the rest (57% vs 73%, p=0.05) and (58% vs 85%, p=0.002). In the multivariate analysis including the IPI variable and myc/bcl-2, myc/bcl-2 overexpression showed an independent prognostic value on OS, HR 3,876(1.58, 9.51), p=0.003.
Conclusion
In our experience the protein overexpression of MYC and BCL-2 had a negative impact on the outcome, specially in the rituximab era with a lower CCR and a significant worse TTP and OS. Further studies on these area are required.
Session topic: E-poster
Keyword(s): BCL2, DLBCL, MYC
Type: Publication Only
Background
.Protein overexpression and rearrangements of myc and bcl-2 genes have been related with an adverse prognosis in diffuse large B-cell lymphoma (DLBCL) patients in the rituximab era. But data are not always consistent and sometimes contradictory.
Aims
to analyze the incidence of MYC and BCL2 protein overexpression in DLBCL as well as to evaluate the prognostic impact in terms of time to progression (TTP) and overall survival (OS).
Methods
We carried out a single institution study with tissue biopsies obtained from patients diagnosed of DLBCL in the period 1994-2011. Tissue fixation and processing were performed using standard methods. Tissue microarrays (TMAs) that contained two representative 2-mm cores from each tumor were prepared. Immunohistochemical stainnings were performed using fully automated protocols. We used the following antibodies: MYC (clone Y69;Roche), BCL2 (clone 124; DAKO). The cut-off level for BCL2 and MYC expression was 50% and 10% respectively. MYC and BCL2 expression were evaluated by an pathologist expert as well as an hematologist. At the same time, MYC and BCL2 expression was evaluated using computerized image analysis with Image Pro Plus 6.0. A mean number of 1000 cells were analyzed per case. TTP and OS curves were built by the Kaplan_Meier method and compared by the log-rank test. Impact of TTP and OS was studied by the Cox regression test. Results: 140 DLBCL patients were included, median age was 70 (23-76), male/female ratio 73/67, Ann Arbor stage III or IV: 73 (52%), high LDH 72 (51%), high β2-microglobulin 62 (44%) low risk IPI 53 pt, int-low 26pt (19%), int-high 31pt (23%), high 28pt (20%) IPI ≥ 3: 59pt (42.1%). 45 patient were treated with CHOP-like regimens and 95 with rituximab-CHOP schedules. Median follow-up (alive pts) was 49 months(12,135).
Results
We observed MYC overexpression (≥10%) in 101pt (72%), BCL2 overexpression (≥50%) in 71pt (50%) and both in 56pt (40%). We did not observe any correlationship between MYC, BCL2 or both overexpression and clinical-biologic baseline characteristics. Patients with MYC and BCL2 overexpression had a lower complete response rate than the rest: 62% versus 76% (p=0.09). Patients with both markers had a worse 5 year TTP: 67% versus 83% (p0.09) and also a worse 5 year OS: 60% versus 79% (p0.05),. When we restricted the analysis to the rituximab-treated patients, patients with both markers had a worse 5-y TTP and OS than the rest (57% vs 73%, p=0.05) and (58% vs 85%, p=0.002). In the multivariate analysis including the IPI variable and myc/bcl-2, myc/bcl-2 overexpression showed an independent prognostic value on OS, HR 3,876(1.58, 9.51), p=0.003.
Conclusion
In our experience the protein overexpression of MYC and BCL-2 had a negative impact on the outcome, specially in the rituximab era with a lower CCR and a significant worse TTP and OS. Further studies on these area are required.
Session topic: E-poster
Keyword(s): BCL2, DLBCL, MYC
Abstract: PB1708
Type: Publication Only
Background
.Protein overexpression and rearrangements of myc and bcl-2 genes have been related with an adverse prognosis in diffuse large B-cell lymphoma (DLBCL) patients in the rituximab era. But data are not always consistent and sometimes contradictory.
Aims
to analyze the incidence of MYC and BCL2 protein overexpression in DLBCL as well as to evaluate the prognostic impact in terms of time to progression (TTP) and overall survival (OS).
Methods
We carried out a single institution study with tissue biopsies obtained from patients diagnosed of DLBCL in the period 1994-2011. Tissue fixation and processing were performed using standard methods. Tissue microarrays (TMAs) that contained two representative 2-mm cores from each tumor were prepared. Immunohistochemical stainnings were performed using fully automated protocols. We used the following antibodies: MYC (clone Y69;Roche), BCL2 (clone 124; DAKO). The cut-off level for BCL2 and MYC expression was 50% and 10% respectively. MYC and BCL2 expression were evaluated by an pathologist expert as well as an hematologist. At the same time, MYC and BCL2 expression was evaluated using computerized image analysis with Image Pro Plus 6.0. A mean number of 1000 cells were analyzed per case. TTP and OS curves were built by the Kaplan_Meier method and compared by the log-rank test. Impact of TTP and OS was studied by the Cox regression test. Results: 140 DLBCL patients were included, median age was 70 (23-76), male/female ratio 73/67, Ann Arbor stage III or IV: 73 (52%), high LDH 72 (51%), high β2-microglobulin 62 (44%) low risk IPI 53 pt, int-low 26pt (19%), int-high 31pt (23%), high 28pt (20%) IPI ≥ 3: 59pt (42.1%). 45 patient were treated with CHOP-like regimens and 95 with rituximab-CHOP schedules. Median follow-up (alive pts) was 49 months(12,135).
Results
We observed MYC overexpression (≥10%) in 101pt (72%), BCL2 overexpression (≥50%) in 71pt (50%) and both in 56pt (40%). We did not observe any correlationship between MYC, BCL2 or both overexpression and clinical-biologic baseline characteristics. Patients with MYC and BCL2 overexpression had a lower complete response rate than the rest: 62% versus 76% (p=0.09). Patients with both markers had a worse 5 year TTP: 67% versus 83% (p0.09) and also a worse 5 year OS: 60% versus 79% (p0.05),. When we restricted the analysis to the rituximab-treated patients, patients with both markers had a worse 5-y TTP and OS than the rest (57% vs 73%, p=0.05) and (58% vs 85%, p=0.002). In the multivariate analysis including the IPI variable and myc/bcl-2, myc/bcl-2 overexpression showed an independent prognostic value on OS, HR 3,876(1.58, 9.51), p=0.003.
Conclusion
In our experience the protein overexpression of MYC and BCL-2 had a negative impact on the outcome, specially in the rituximab era with a lower CCR and a significant worse TTP and OS. Further studies on these area are required.
Session topic: E-poster
Keyword(s): BCL2, DLBCL, MYC
Type: Publication Only
Background
.Protein overexpression and rearrangements of myc and bcl-2 genes have been related with an adverse prognosis in diffuse large B-cell lymphoma (DLBCL) patients in the rituximab era. But data are not always consistent and sometimes contradictory.
Aims
to analyze the incidence of MYC and BCL2 protein overexpression in DLBCL as well as to evaluate the prognostic impact in terms of time to progression (TTP) and overall survival (OS).
Methods
We carried out a single institution study with tissue biopsies obtained from patients diagnosed of DLBCL in the period 1994-2011. Tissue fixation and processing were performed using standard methods. Tissue microarrays (TMAs) that contained two representative 2-mm cores from each tumor were prepared. Immunohistochemical stainnings were performed using fully automated protocols. We used the following antibodies: MYC (clone Y69;Roche), BCL2 (clone 124; DAKO). The cut-off level for BCL2 and MYC expression was 50% and 10% respectively. MYC and BCL2 expression were evaluated by an pathologist expert as well as an hematologist. At the same time, MYC and BCL2 expression was evaluated using computerized image analysis with Image Pro Plus 6.0. A mean number of 1000 cells were analyzed per case. TTP and OS curves were built by the Kaplan_Meier method and compared by the log-rank test. Impact of TTP and OS was studied by the Cox regression test. Results: 140 DLBCL patients were included, median age was 70 (23-76), male/female ratio 73/67, Ann Arbor stage III or IV: 73 (52%), high LDH 72 (51%), high β2-microglobulin 62 (44%) low risk IPI 53 pt, int-low 26pt (19%), int-high 31pt (23%), high 28pt (20%) IPI ≥ 3: 59pt (42.1%). 45 patient were treated with CHOP-like regimens and 95 with rituximab-CHOP schedules. Median follow-up (alive pts) was 49 months(12,135).
Results
We observed MYC overexpression (≥10%) in 101pt (72%), BCL2 overexpression (≥50%) in 71pt (50%) and both in 56pt (40%). We did not observe any correlationship between MYC, BCL2 or both overexpression and clinical-biologic baseline characteristics. Patients with MYC and BCL2 overexpression had a lower complete response rate than the rest: 62% versus 76% (p=0.09). Patients with both markers had a worse 5 year TTP: 67% versus 83% (p0.09) and also a worse 5 year OS: 60% versus 79% (p0.05),. When we restricted the analysis to the rituximab-treated patients, patients with both markers had a worse 5-y TTP and OS than the rest (57% vs 73%, p=0.05) and (58% vs 85%, p=0.002). In the multivariate analysis including the IPI variable and myc/bcl-2, myc/bcl-2 overexpression showed an independent prognostic value on OS, HR 3,876(1.58, 9.51), p=0.003.
Conclusion
In our experience the protein overexpression of MYC and BCL-2 had a negative impact on the outcome, specially in the rituximab era with a lower CCR and a significant worse TTP and OS. Further studies on these area are required.
Session topic: E-poster
Keyword(s): BCL2, DLBCL, MYC
{{ help_message }}
{{filter}}