AIM: Diffuse large B cell lymphoma (DLBCL) is the most common lymphoid malignancy in the western hemisphere, and is characterised by a highly variable outcome that impedes individual risk assessment. Lacking reliable biomarkers, the international prognostic index (IPI) has been the most reliable factor to predict survival and stratify patients for therapy. The aim of this study was to investigate the frequency and potential prognostic role of BCL2 aberrations on the chromosomal level and the protein level in a large DLBCL collective. METHODS: Fluorescence in situ hybridisation (FISH) with commercially available dual-colour break-apart probes and immunohistochemistry were used to assess BCL2 gene abnormalities and bcl2 protein expression on validated tissue microarrays containing 224 well-characterised cases of primary DLBCL. RESULTS: FISH analysis of BCL2 revealed a break in 40/215 cases (19%) and a gain in 66/171 (39%) cases. Only BCL2 gains correlated with bcl2 protein expression (p = 0.001). Presence of any BCL2 gene abnormality, particularly gains, correlated independently of the IPI with a significantly worse prognosis in DLBCL of non-germinal centre (non-GC) phenotype as opposed to DLBCL of non-GC type without this genetic alteration (p = 0.003). DLBCL of germinal centre phenotype did not show this association. CONCLUSIONS: Cases of DLBCL of the non-GC type with BCL2 gene aberration are accompanied by a significantly worse prognosis as opposed to cases without such gene abnormalities. It may be helpful to asses BCL2 gene abnormalities by FISH in addition to assessing established parameters for individual risk estimation in DLBCL.
AIM: Diffuse large B cell lymphoma (DLBCL) is the most common lymphoid malignancy in the western hemisphere, and is characterised by a highly variable outcome that impedes individual risk assessment. Lacking reliable biomarkers, the international prognostic index (IPI) has been the most reliable factor to predict survival and stratify patients for therapy. The aim of this study was to investigate the frequency and potential prognostic role of BCL2 aberrations on the chromosomal level and the protein level in a large DLBCL collective. METHODS: Fluorescence in situ hybridisation (FISH) with commercially available dual-colour break-apart probes and immunohistochemistry were used to assess BCL2 gene abnormalities and bcl2 protein expression on validated tissue microarrays containing 224 well-characterised cases of primary DLBCL. RESULTS: FISH analysis of BCL2 revealed a break in 40/215 cases (19%) and a gain in 66/171 (39%) cases. Only BCL2 gains correlated with bcl2 protein expression (p = 0.001). Presence of any BCL2 gene abnormality, particularly gains, correlated independently of the IPI with a significantly worse prognosis in DLBCL of non-germinal centre (non-GC) phenotype as opposed to DLBCL of non-GC type without this genetic alteration (p = 0.003). DLBCL of germinal centre phenotype did not show this association. CONCLUSIONS: Cases of DLBCL of the non-GC type with BCL2 gene aberration are accompanied by a significantly worse prognosis as opposed to cases without such gene abnormalities. It may be helpful to asses BCL2 gene abnormalities by FISH in addition to assessing established parameters for individual risk estimation in DLBCL.
Authors: Javeed Iqbal; Paul N Meyer; Lynette M Smith; Nathalie A Johnson; Julie M Vose; Timothy C Greiner; Joseph M Connors; Louis M Staudt; Lisa Rimsza; Elaine Jaffe; Andreas Rosenwald; German Ott; Jan Delabie; Elias Campo; Rita M Braziel; James R Cook; Raymond R Tubbs; Randy D Gascoyne; James O Armitage; Dennis D Weisenburger; Wing C Chan Journal: Clin Cancer Res Date: 2011-09-20 Impact factor: 12.531
Authors: Carlo Visco; Alexander Tzankov; Zijun Y Xu-Monette; Roberto N Miranda; Yu Chuan Tai; Yan Li; Wei-min Liu; Emanuele S G d'Amore; Yong Li; Santiago Montes-Moreno; Karen Dybkær; April Chiu; Attilio Orazi; Youli Zu; Govind Bhagat; Huan-You Wang; Cherie H Dunphy; Eric D His; X Frank Zhao; William W L Choi; Xiaoying Zhao; J Han van Krieken; Qin Huang; Weiyun Ai; Stacey O'Neill; Maurilio Ponzoni; Andres J M Ferreri; Brad S Kahl; Jane N Winter; Ronald S Go; Stephan Dirnhofer; Miguel A Piris; Michael B Møller; Lin Wu; L Jeffrey Medeiros; Ken H Young Journal: Haematologica Date: 2012-08-28 Impact factor: 9.941