title: Expression and phosphorylation of eukaryotic translation initiation factor 4E binding protein 1 in B-cell lymphomas and reactive lymphoid tissues.
abstract: BACKGROUND
  Cap-mediated messenger RNA translation controlled by the eukaryotic initiation factor 4F (eIF-4F) complex plays a key role in human cancer. eIF-4F activity is controlled by a repressor binding protein (4E-BP1), which promotes translation when phosphorylated.
  
  
  OBJECTIVE
  To examine the level of expression and phosphorylation of 4E-BP1 in various subtypes of B-cell lymphoma and reactive lymphoid tissues.
  
  
  METHODS
  Archival formalin-fixed, paraffin-embedded B-cell lymphoma samples and reactive lymphoid tissues were immunostained and examined for expression of 4E-BP1 and phosphorylated 4E-BP1. Expression of components of the eIF-4F complex and unphosphorylated and phosphorylated 4E-BP1 was confirmed using Western immunoblotting on lysates of frozen lymphoma samples and reactive tissues.
  
  
  RESULTS
  Immunohistochemical analysis demonstrated weak to undetectable 4E-BP1 staining within benign, reactive germinal centers (N = 10). In contrast, 4E-BP1 was consistently expressed (moderate to strong staining) in 98% of various subtypes of mature B-cell lymphoma (N = 50). 4E-BP1 expression was also demonstrable in all 4 lymph nodes with in situ or partial involvement by follicular lymphoma and in all 12 cases of BCL2-negative lymphoma. The level of phosphorylation of 4E-BP1 in lymphomas, evaluated by immunohistochemistry, was heterogeneous.
  
  
  CONCLUSIONS
  The immunohistochemical expression pattern of 4E-BP1 exhibits regional and cellular specificity in reactive lymphoid tissues and may offer a diagnostic tool for distinguishing reactive follicles from neoplastic B-cell proliferations.
authors.affiliation: Hematology-Oncology Section, Departments of Medicine, Veterans Administration Medical Center, Minneapolis, Minnesota, USA.
authors.forename: Dhatri
authors.initials: D
authors.lastname: Kodali
authors.forename: Ajay
authors.initials: A
authors.lastname: Rawal
authors.forename: Mary J
authors.initials: MJ
authors.lastname: Ninan
authors.forename: Manish R
authors.initials: MR
authors.lastname: Patel
authors.forename: Hector
authors.initials: H
authors.lastname: Mesa
authors.forename: Dennis
authors.initials: D
authors.lastname: Knapp
authors.forename: Bertram
authors.initials: B
authors.lastname: Schnitzer
authors.forename: Robert A
authors.initials: RA
authors.lastname: Kratzke
authors.forename: Pankaj
authors.initials: P
authors.lastname: Gupta
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism; D015153:Blotting, Western; D018797:Cell Cycle Proteins; D018858:Germinal Center / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008198:Lymph Nodes / Q000378:metabolism / Q000473:pathology; D008221:Lymphoid Tissue / Q000378:metabolism* / Q000473:pathology; D016393:Lymphoma, B-Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008224:Lymphoma, Follicular / Q000378:metabolism / Q000473:pathology; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D019310:Pseudolymphoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D012315:RNA Caps / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; C087000:EIF4EBP1 protein, human; D010750:Phosphoproteins; D012315:RNA Caps