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KMID : 0378120030300020137
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Chungnam Medical Journal
2003 Volume.30 No. 2 p.137 ~ p.151
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Clinical Significance of Expression of Biomarker in Patients with Diffuse Large B-Cell Lymphoma
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Kim Sam-Yong
Kwak Seung-Keon
Park Sang-Eun
Yun Hwan-Jung
Jo Deog-Yeon
Kim Jin-Man
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Abstract
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Clinical Significanceof Expression of Biomarkers in Patients with Diffuse Large B-cell Lymphoma
Diffuse large B-cell lymphoma(DLBL) is the most common type of lymphoma in Korea, representing about 50% of non-Hodgkin’s Lymphomas. Although DLBL is usually considered as a specific category, the diversity in clinical presentation, morphology, genetic and molecular alterations strongly suggest that these tumors represent a heterogeneous group of neoplasia rather than a single clinicopathological entity. Clinical prognostic systems, including the International Prognostic Index (IPI), although useful to assess overall prognosis, embraces patients with heterogeneous prognoses. It is likely that the prognostic assessment of patients with DLBL might be improved by using biological features.
During the last decade, most studies dealing with the heterogeneity of DLBL have focused on individual protein expression and molecular alterations. The expression of individual antigens related to different stages of B-cell differentiation, including CD10, bcl-6, and IRF-4, may help to define groups of tumors with different clinical and pathological characteristics.
To determine the clinical significance and prognostic value of individual biomarker expression and the biomarker expression patterns according to germinal center subgroup or post-germinal center subgroup of DLBL as defined by a relatively small number of single antigens, we studied 26 patients with de novo DLBL, whose archival pathology specimen were available for immunohistochemistry studies, atChungnam National University Hospital from September 1992 to December 2000. Archival specimens from each patient were immunostained with respective antibodies for CD10, bcl-6, IRF-4, bcl-2 antigens. Two immunophenotyping profiles were distinguished according to the pattern of differentiation; germinal center(GC;CD10/Bcl-6+/IRF-4-) subgroup or postgerminal center (pGC ; CD10/bcl-6/IRF4+) subgroup.
The results are as follows;
1) Baseline characteristics of patients were ; median age of patients was 56(range ; 37-69). 17 patients(65.4%) were male. 5 patients(l9.2%) had ’B’ symptoms. Stages were as follows ; stage Ⅰ2 patients(7.7%), stage Ⅱ 11 patients(42.3%), stage Ⅲ 5 patients(l9.2%), stage Ⅳ 8 patients(30.8%). 11 patients (42.3%) had elevated LDH levels. 25 patients(96.2%) had ECOG performance grade 0-Ⅱ and 1 patient had grade Ⅲ. 5 patients(l9.2%) bad bulky disease.
2) The results of immunohistochemical study were as follows ; positive bcl-2 staining in 17 patients(65.4%), positive bcl-6 in 20 patients(76.1%), positive CD10 in 5 patients(l9.2%), positive IRF-4 staining in 8 patients (30.8%).
3) After a median follow up duration of 48 months, the median survival duration was 44 months with a range of survival of 1-100+ months. 5-year overall survival rate was 32% by Kaplan-Meier method.
4) The clinical factors affecting survival were elevated serum LDH level, B symptoms, bulky disease, stage at diagnosis and ECOG performance status
5) Among the biomarkers, only bcl-2 expression affected survival of DLBL patients
6) The germinal center like subgroup had superior survival than post-germinal center like subgroup but had no statistical significance.
7) Multivariate analysis showed that bcl-2 and serum LDH level had siginificance on survival
Conclusion
In addition to the known clinical prognostic factors, immunohistochemically defined characteristics such as bcl-2 expressionin DLBL is important and subgroups(germinal center or post-germinal center subgroup) of DLBL may have importance in predicting prognosis of DLBL patients
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KEYWORD
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Diffuse large B-cell lymphoma, International prognosis index, CD 10, Bcl-6, IRF-4, Bcl-2, Germinal center subgroup and post germinal center subgroup
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