title: Immunohistochemical and molecular characteristics with prognostic significance in diffuse large B-cell lymphoma.
abstract: Diffuse large B-cell lymphoma (DLBCL) is an aggressive non-Hodgkin lymphoma with marked biologic heterogeneity. We analyzed 100 cases of DLBCL to evaluate the prognostic value of immunohistochemical markers derived from the gene expression profiling-defined cell origin signature, including MYC, BCL2, BCL6, and FOXP1 protein expression. We also investigated genetic alterations in BCL2, BCL6, MYC and FOXP1 using fluorescence in situ hybridization and assessed their prognostic significance. BCL6 rearrangements were detected in 29% of cases, and BCL6 gene alteration (rearrangement and/or amplification) was associated with the non-germinal center B subtype (non-GCB). BCL2 translocation was associated with the GCB phenotype, and BCL2 protein expression was associated with the translocation and/or amplification of 18q21. MYC rearrangements were detected in 15% of cases, and MYC protein expression was observed in 29% of cases. FOXP1 expression, mainly of the non-GCB subtype, was demonstrated in 37% of cases. Co-expression of the MYC and BCL2 proteins, with non-GCB subtype predominance, was observed in 21% of cases. We detected an association between high FOXP1 expression and a high proliferation rate as well as a significant positive correlation between MYC overexpression and FOXP1 overexpression. MYC, BCL2 and FOXP1 expression were significant predictors of overall survival. The co-expression of MYC and BCL2 confers a poorer clinical outcome than MYC or BCL2 expression alone, whereas cases negative for both markers had the best outcomes. Our study confirms that DLBCL, characterized by the co-expression of MYC and BCL2 proteins, has a poor prognosis and establishes a significant positive correlation with MYC and FOXP1 over-expression in this entity.
authors.affiliation: Laboratory of Molecular Pathology, Instituto de Investigación Sanitaria, Hospital Universitario Puerta de Hierro-Majadahonda, Madrid, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Bellas
authors.affiliation: Laboratory of Molecular Pathology, Instituto de Investigación Sanitaria, Hospital Universitario Puerta de Hierro-Majadahonda, Madrid, Spain.
authors.forename: Diego
authors.initials: D
authors.lastname: García
authors.affiliation: Laboratory of Molecular Pathology, Instituto de Investigación Sanitaria, Hospital Universitario Puerta de Hierro-Majadahonda, Madrid, Spain.
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Vicente
authors.affiliation: Laboratory of Molecular Pathology, Instituto de Investigación Sanitaria, Hospital Universitario Puerta de Hierro-Majadahonda, Madrid, Spain.
authors.forename: Linah
authors.initials: L
authors.lastname: Kilany
authors.affiliation: Unidad de Bioestadística Clínica, Hospital Universitario Ramón y Cajal, CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain.
authors.forename: Victor
authors.initials: V
authors.lastname: Abraira
authors.affiliation: Department of Hematology, Hospital Universitario Puerta de Hierro-Majadahonda, Madrid, Spain.
authors.forename: Belen
authors.initials: B
authors.lastname: Navarro
authors.affiliation: Medical Oncology Service, Onco-hematology Research Unit, Instituto de Investigación Sanitaria, Hospital Universitario Puerta de Hierro-Majadahonda, Madrid, Spain.
authors.forename: Mariano
authors.initials: M
authors.lastname: Provencio
authors.affiliation: Laboratory of Molecular Pathology, Instituto de Investigación Sanitaria, Hospital Universitario Puerta de Hierro-Majadahonda, Madrid, Spain.
authors.forename: Paloma
authors.initials: P
authors.lastname: Martín
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D015321:Gene Rearrangement; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism; D016019:Survival Analysis; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D016271:Proto-Oncogene Proteins c-myc