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CORRELATION BETWEEN CLINICAL ANT PATHOLOGICAL VARIABLES WITH IMMUNOHISTOCHEMICALLY DIFFERENTIATED MOLECULAR SUBTYPES OF DIFFUSE LARGE B-CELL LYMPHOMA
Author(s): ,
Emina Hadzimesic Suljovic
Affiliations:
Clinical Center University of Sarajevo, Hematology Clinic,Sarajevo,Bosnia and Herzegovina
,
Svjetlana Radovic
Affiliations:
Medical Faculty University of Sarajevo,Sarajevo,Bosnia and Herzegovina
,
Nermina Obralic
Affiliations:
Clinical Center University of Sarajevo, Hematology Clinic,Sarajevo,Bosnia and Herzegovina
,
Amina Kozaric
Affiliations:
Clinical Center University of Sarajevo, Hematology Clinic,Sarajevo,Bosnia and Herzegovina
,
Nurija Bilalovic
Affiliations:
Clinical Center University of Sarajevo, Hematology Clinic,Sarajevo,Bosnia and Herzegovina
Alma Sofo-Hafizović
Affiliations:
Clinical Center University of Sarajevo, Hematology Clinic,Sarajevo,Bosnia and Herzegovina
(Abstract release date: 05/17/18) EHA Library. Suljovic Hadzimesic E. 06/14/18; 216596; PB2347
Emina Suljovic Hadzimesic
Emina Suljovic Hadzimesic
Contributions
Abstract

Abstract: PB2347

Type: Publication Only

Background
Gene expression profiling has made a distinction between the two pathological entities of the DLBCL, ABC DLBCL and GCB-DLBCL. Genetic profiling is still far from routine clinical practice, so using immunohistochemical methods, identification of GCB and ABC phenotype has been translated into clinically feasible approach by developing algorithms for defining the molecular subtypes based on the expression of immunohistochemical markers defining subgroups as GCB and non-GCB. IPI (International Prognostic Index) remains the most accurate prognostic model due to inconsistent results of prognostic models based on biomarkers, and research focus is directed to upgrading the IPI models and  to correlations between clinical parameters and biomarkers with biological characteristics of the disease.

 

Aims
To determine the correlation between clinical and pathological variables with immunohistochemically differentiated molecular subtypes of DLBCL.

Methods
 We have analyzed 50 patients with DLBCL for the expression of bcl-2, bcl-6, CD10, MUM1 and Ki-67 Patients were divided into two groups, the non-GCB, GCB group or favorable group 1 and unfavorable group 2, according to Hans's algorithm and Muris's algorithm. Clinical-pathological, biochemical parameters of disease have been correlated with subgroups of DLBCL and biomarkers individually. The impact of the expression of bcl-2, bcl-6, CD10, MUM1 and Ki67 on IPI-highest score in multiple regression analysis, afterwards in regression equation and variance analyse.

Results
Patients younger than 60 years are significantly more non-GCB subtype, avarage age 46.29 years. CD10 and MUM1 are significantly more present in non-GCB subtype and in Group2.  Positive correlation between bcl6 and extranodal localisation was proved (p>0.05). In the analysis of correlation of pathological variables and immunohistohemically determined molecular subtypes, difference in the size of the nucleus as well as the correlation between the subtypes to Hans (p<0.05), but not Muris (p>0.05) was demonstrated. 91.7% of non-GCB patients had the size of nucleus II. Difference in the incidence rate of more than one extranodal site in non-GCB groups per Hans was found (p = 0.045). POsitive correlation was found between increased values of lactat dehidrogenase and beta2mikcroglobulin  and Group2.  GCB phenotype showed positive correlation with good-risk patients identified by IPI. Multiple regressional analysis proved impact of biomarkers on IPI. The mutual impact of bcl-2, bcl-6, MUM1, Ki67 is significantlyrelated to poor-risk IPI patients

Conclusion

A more aggressive type of the disease and more severe clinical features are significantly more common among patients in the subgroup of non-GCB or group 2, DLBCL. Non-GCB subgroup and group 2 were associated with a higher clinical stage (III / IV), lower Karnofsky index or higher ECOG performance status, number of extranodal localization of more than one locus, elevated lactate dehydrogenase value, increased value of Ki67 and increased value of beta2microglobulin.

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

Keyword(s): BCL2, BCL6, DLBCL, Ki-67

Abstract: PB2347

Type: Publication Only

Background
Gene expression profiling has made a distinction between the two pathological entities of the DLBCL, ABC DLBCL and GCB-DLBCL. Genetic profiling is still far from routine clinical practice, so using immunohistochemical methods, identification of GCB and ABC phenotype has been translated into clinically feasible approach by developing algorithms for defining the molecular subtypes based on the expression of immunohistochemical markers defining subgroups as GCB and non-GCB. IPI (International Prognostic Index) remains the most accurate prognostic model due to inconsistent results of prognostic models based on biomarkers, and research focus is directed to upgrading the IPI models and  to correlations between clinical parameters and biomarkers with biological characteristics of the disease.

 

Aims
To determine the correlation between clinical and pathological variables with immunohistochemically differentiated molecular subtypes of DLBCL.

Methods
 We have analyzed 50 patients with DLBCL for the expression of bcl-2, bcl-6, CD10, MUM1 and Ki-67 Patients were divided into two groups, the non-GCB, GCB group or favorable group 1 and unfavorable group 2, according to Hans's algorithm and Muris's algorithm. Clinical-pathological, biochemical parameters of disease have been correlated with subgroups of DLBCL and biomarkers individually. The impact of the expression of bcl-2, bcl-6, CD10, MUM1 and Ki67 on IPI-highest score in multiple regression analysis, afterwards in regression equation and variance analyse.

Results
Patients younger than 60 years are significantly more non-GCB subtype, avarage age 46.29 years. CD10 and MUM1 are significantly more present in non-GCB subtype and in Group2.  Positive correlation between bcl6 and extranodal localisation was proved (p>0.05). In the analysis of correlation of pathological variables and immunohistohemically determined molecular subtypes, difference in the size of the nucleus as well as the correlation between the subtypes to Hans (p<0.05), but not Muris (p>0.05) was demonstrated. 91.7% of non-GCB patients had the size of nucleus II. Difference in the incidence rate of more than one extranodal site in non-GCB groups per Hans was found (p = 0.045). POsitive correlation was found between increased values of lactat dehidrogenase and beta2mikcroglobulin  and Group2.  GCB phenotype showed positive correlation with good-risk patients identified by IPI. Multiple regressional analysis proved impact of biomarkers on IPI. The mutual impact of bcl-2, bcl-6, MUM1, Ki67 is significantlyrelated to poor-risk IPI patients

Conclusion

A more aggressive type of the disease and more severe clinical features are significantly more common among patients in the subgroup of non-GCB or group 2, DLBCL. Non-GCB subgroup and group 2 were associated with a higher clinical stage (III / IV), lower Karnofsky index or higher ECOG performance status, number of extranodal localization of more than one locus, elevated lactate dehydrogenase value, increased value of Ki67 and increased value of beta2microglobulin.

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

Keyword(s): BCL2, BCL6, DLBCL, Ki-67

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