title: Immunohistochemical profiling based on Bcl-2, CD10 and MUM1 expression improves risk stratification in patients with primary nodal diffuse large B cell lymphoma.
abstract: Clinical outcome in patients with diffuse large B cell lymphomas (DLBCL) is poorly predictable. Expression of proteins related to germinal centre B (GCB) cell or activated B cells (ABC) and expression of apoptosis-regulating proteins Bcl-2 and XIAP have been found previously to be strongly associated with clinical outcome. In this study we aimed to develop an algorithm based on expression of GCB/ABC-related proteins CD10, Bcl-6 and MUM1 and apoptosis-inhibiting proteins Bcl-2, XIAP and cFLIP for optimal stratification of DLBCL patients into prognostically favourable and unfavourable groups. Expression of CD10 and cFLIP was associated with better overall survival (both p = 0.03), whereas expression of MUM1, Bcl-2 and XIAP was associated with poor clinical outcome (p = 0.01, p = 0.0007 and p = 0.03, respectively). Multivariate analysis revealed that Bcl-2 was the strongest prognostic marker followed by CD10 and MUM1. Stratification of patients according to a new algorithm based on expression of these three markers improved patient risk stratification into low and particularly high clinical risk groups (p = 0.04 and p < 0.0001, respectively). We conclude that, in our group of primary nodal DLBCLs, a new algorithm, based on expression of the apoptosis-inhibiting protein Bcl-2 and the GCB/ABC-related proteins CD10 and MUM1, strongly predicts outcome in International Prognostic Index (IPI)-low and -high patients. Its predictive power is stronger than previously published algorithms based on only GCB/ABC- or apoptosis-regulating proteins.
authors.affiliation: Department of Pathology, VU Medical Centre, Amsterdam, The Netherlands.
authors.forename: J J F
authors.initials: JJ
authors.lastname: Muris
authors.forename: C J L M
authors.initials: CJ
authors.lastname: Meijer
authors.forename: W
authors.initials: W
authors.lastname: Vos
authors.forename: J H J M
authors.initials: JH
authors.lastname: van Krieken
authors.forename: N M
authors.initials: NM
authors.lastname: Jiwa
authors.forename: G J
authors.initials: GJ
authors.lastname: Ossenkoppele
authors.forename: J J
authors.initials: JJ
authors.lastname: Oudejans
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D014408:Biomarkers, Tumor / Q000378:metabolism*; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D050835:Interferon Regulatory Factors / Q000378:metabolism; D016393:Lymphoma, B-Cell / Q000378:metabolism*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism*; D015260:Neprilysin / Q000378:metabolism; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D016019:Survival Analysis; D000099218:Interferon Regulatory Factor-4
chemical_list: D014408:Biomarkers, Tumor; D050835:Interferon Regulatory Factors; D009363:Neoplasm Proteins; D015260:Neprilysin; D019253:Proto-Oncogene Proteins c-bcl-2; D000099218:Interferon Regulatory Factor-4