Loss of HLA-DR expression and immunoblastic morphology predict adverse outcome in diffuse large B-cell lymphoma - analyses of cases from two prospective randomized clinical trials - Publication

Publication

Loss of HLA-DR expression and immunoblastic morphology predict adverse outcome in diffuse large B-cell lymphoma - analyses of cases from two prospective randomized clinical trials

Journal Paper/Review - Nov 1, 2009

Bernd Heinz-Wolfram, Möller Peter, Cogliatti Sergio B., Pfreundschuh Michael, Schmitz Norbert, Trümper Lorenz, Höller Silvia, Löffler Markus, Feller Alfred C, Barth Thomas F E, Müller-Hermelink Hans-Konrad, Rosenwald Andreas, Ziepert Marita, Thorns Christoph, Klapper Wolfram, Wacker Hans-Heinrich, Hummel Michael, Stein Harald, Hansmann Martin-Leo, Ott German, German High Grade Non-Hodgkin's Lymphoma Study Group (DSHNHL)

Citation

Bernd H, Möller P, Cogliatti S, Pfreundschuh M, Schmitz N, Trümper L, Höller S, Löffler M, Feller A, Barth T, Müller-Hermelink H, Rosenwald A, Ziepert M, Thorns C, Klapper W, Wacker H, Hummel M, Stein H, Hansmann M, Ott G, German High Grade Non-Hodgkin's Lymphoma Study Group (DSHNHL). Loss of HLA-DR expression and immunoblastic morphology predict adverse outcome in diffuse large B-cell lymphoma - analyses of cases from two prospective randomized clinical trials. Haematologica 2009; 94:1569-80.

Type

Journal Paper/Review (English)

Journal

Haematologica 2009; 94

Publication Date

Nov 1, 2009

Issn Electronic

1592-8721

Pages

1569-80

Brief description/objective

BACKGROUND: Research on prognostically relevant immunohistochemical markers in diffuse large B-cell lymphomas has mostly been performed on retrospectively collected clinical data. This is also true for immunohistochemical classifiers that are thought to reflect the cell-of-origin subclassification of gene expression studies. In order to obtain deeper insight into the heterogeneous prognosis of diffuse large B-cell lymphomas and to validate a previously published immunohistochemical classifier, we analyzed data from a large set of cases from prospective clinical trials with long-term follow-up. DESIGN AND METHODS: We performed morphological and extensive immunohistochemical analyses in 414 cases of diffuse large B-cell lymphoma from two prospective randomized clinical trials (NHL-B1/B2, Germany). Classification into germinal center and non-germinal center subtypes of B-cell lymphoma was based on the expression pattern of CD10, BCL6, and IRF4. Multivariate analyses were performed adjusting for the factors in the International Prognostic Index. RESULTS: Analyzing 20 different epitopes on tissue microarrays, expression of HLA-DR, presence of CD23(+) follicular dendritic cell meshworks, and monotypic light chain expression emerged as International Prognostic Index-independent markers of superior overall survival. Immunoblastic morphology was found to be related to poor event-free survival. The non-germinal center subtype, according to the three-epitope classifier (CD10, BCL6, and IRF4) did not have prognostic relevance when adjusted for International Prognostic Index factors (relative risk=1.2, p=0.328 for overall survival; and relative risk=1.1, p=0.644 for event-free survival). CONCLUSIONS: The previously reported International Prognostic Index-independent prognostic value of stratification into germinal center/non-germinal center B-cell lymphoma using the expression pattern of CD10, BCL6, and IRF4 was not reproducible in our series. However, other markers and the morphological subtype appear to be of prognostic value.