title: A new immunostain algorithm classifies diffuse large B-cell lymphoma into molecular subtypes with high accuracy.
abstract: OBJECTIVE
  Hans and coworkers previously developed an immunohistochemical algorithm with approximately 80% concordance with the gene expression profiling (GEP) classification of diffuse large B-cell lymphoma (DLBCL) into the germinal center B-cell-like (GCB) and activated B-cell-like (ABC) subtypes. Since then, new antibodies specific to germinal center B-cells have been developed, which might improve the performance of an immunostain algorithm.
  
  
  METHODS
  We studied 84 cases of cyclophosphamide-doxorubicin-vincristine-prednisone (CHOP)-treated DLBCL (47 GCB, 37 ABC) with GCET1, CD10, BCL6, MUM1, FOXP1, BCL2, MTA3, and cyclin D2 immunostains, and compared different combinations of the immunostaining results with the GEP classification. A perturbation analysis was also applied to eliminate the possible effects of interobserver or intraobserver variations. A separate set of 63 DLBCL cases treated with rituximab plus CHOP (37 GCB, 26 ABC) was used to validate the new algorithm.
  
  
  RESULTS
  A new algorithm using GCET1, CD10, BCL6, MUM1, and FOXP1 was derived that closely approximated the GEP classification with 93% concordance. Perturbation analysis indicated that the algorithm was robust within the range of observer variance. The new algorithm predicted 3-year overall survival of the validation set [GCB (87%) versus ABC (44%); P < 0.001], simulating the predictive power of the GEP classification. For a group of seven primary mediastinal large B-cell lymphoma, the new algorithm is a better prognostic classifier (all "GCB") than the Hans' algorithm (two GCB, five non-GCB).
  
  
  CONCLUSIONS
  Our new algorithm is significantly more accurate than the Hans' algorithm and will facilitate risk stratification of DLBCL patients and future DLBCL research using archival materials.
authors.affiliation: Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, Nebraska 68198-3135, USA.
authors.forename: William W L
authors.initials: WW
authors.lastname: Choi
authors.forename: Dennis D
authors.initials: DD
authors.lastname: Weisenburger
authors.forename: Timothy C
authors.initials: TC
authors.lastname: Greiner
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Piris
authors.forename: Alison H
authors.initials: AH
authors.lastname: Banham
authors.forename: Jan
authors.initials: J
authors.lastname: Delabie
authors.forename: Rita M
authors.initials: RM
authors.lastname: Braziel
authors.forename: Huimin
authors.initials: H
authors.lastname: Geng
authors.forename: Javeed
authors.initials: J
authors.lastname: Iqbal
authors.forename: Georg
authors.initials: G
authors.lastname: Lenz
authors.forename: Julie M
authors.initials: JM
authors.lastname: Vose
authors.forename: Christine P
authors.initials: CP
authors.lastname: Hans
authors.forename: Kai
authors.initials: K
authors.lastname: Fu
authors.forename: Lynette M
authors.initials: LM
authors.lastname: Smith
authors.forename: Min
authors.initials: M
authors.lastname: Li
authors.forename: Zhongfeng
authors.initials: Z
authors.lastname: Liu
authors.forename: Randy D
authors.initials: RD
authors.lastname: Gascoyne
authors.forename: Andreas
authors.initials: A
authors.lastname: Rosenwald
authors.forename: German
authors.initials: G
authors.lastname: Ott
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Rimsza
authors.forename: Elias
authors.initials: E
authors.lastname: Campo
authors.forename: Elaine S
authors.initials: ES
authors.lastname: Jaffe
authors.forename: David L
authors.initials: DL
authors.lastname: Jaye
authors.forename: Louis M
authors.initials: LM
authors.lastname: Staudt
authors.forename: Wing C
authors.initials: WC
authors.lastname: Chan
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D003520:Cyclophosphamide / Q000627:therapeutic use; D004317:Doxorubicin / Q000627:therapeutic use; D005260:Female; D020869:Gene Expression Profiling; D018858:Germinal Center / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods*; D053208:Kaplan-Meier Estimate; D016403:Lymphoma, Large B-Cell, Diffuse / Q000145:classification* / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D011241:Prednisone / Q000627:therapeutic use; D014750:Vincristine / Q000627:therapeutic use
chemical_list: D014408:Biomarkers, Tumor; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone
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