A new immunostain algorithm classifies diffuse large B-cell lymphoma into molecular subtypes with high accuracy.
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.
Choi
William W L
WW
Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, Nebraska 68198-3135, USA.
Weisenburger
Dennis D
DD
Greiner
Timothy C
TC
Piris
Miguel A
MA
Banham
Alison H
AH
Delabie
Jan
J
Braziel
Rita M
RM
Geng
Huimin
H
Iqbal
Javeed
J
Lenz
Georg
G
Vose
Julie M
JM
Hans
Christine P
CP
Fu
Kai
K
Smith
Lynette M
LM
Li
Min
M
Liu
Zhongfeng
Z
Gascoyne
Randy D
RD
Rosenwald
Andreas
A
Ott
German
G
Rimsza
Lisa M
LM
Campo
Elias
E
Jaffe
Elaine S
ES
Jaye
David L
DL
Staudt
Louis M
LM
Chan
Wing C
WC
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
D014408:Biomarkers, Tumor; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone
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