Immunohistochemical methods for predicting cell of origin and survival in patients with diffuse large B-cell lymphoma treated with rituximab.
OBJECTIVE
Patients with diffuse large B-cell lymphoma (DLBCL) can be divided into prognostic groups based on the cell of origin of the tumor as determined by microarray analysis. Various immunohistochemical algorithms have been developed to replicate these microarray results and/or stratify patients according to survival. This study compares some of those algorithms and also proposes some modifications.


METHODS
Two-hundred and sixty-two cases of de novo DLBCL treated with rituximab and cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or CHOP-like therapy were examined.


RESULTS
The Choi algorithm and Hans algorithm had high concordance with the microarray results. Modifications of the Choi and Hans algorithms for ease of use still retained high concordance with the microarray results. Although the Nyman and Muris algorithms had high concordance with the microarray results, each had a low value for either sensitivity or specificity. The use of LMO2 alone showed the lowest concordance with the microarray results. A new algorithm (Tally) using a combination of antibodies, but without regard to the order of examination, showed the greatest concordance with microarray results. All of the algorithms divided patients into groups with significantly different overall and event-free survivals, but with different hazard ratios. With the exception of the Nyman algorithm, this survival prediction was independent of the International Prognostic Index. Although the Muris algorithm had prognostic significance, it misclassified a large number of cases with activated B-cell type DLBCL.


CONCLUSIONS
The Tally algorithm showed the best concordance with the microarray data while maintaining prognostic significance and ease of use.
University of Nebraska Medical Center, Omaha, NE 68198-3135, USA. pnm105@hotmail.com
Paul N
PN
Meyer
Kai
K
Fu
Timothy C
TC
Greiner
Lynette M
LM
Smith
Jan
J
Delabie
Randy D
RD
Gascoyne
German
G
Ott
Andreas
A
Rosenwald
Rita M
RM
Braziel
Elias
E
Campo
Julie M
JM
Vose
Georg
G
Lenz
Louis M
LM
Staudt
Wing C
WC
Chan
Dennis D
DD
Weisenburger
D000465:Algorithms; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D006801:Humans; D007150:Immunohistochemistry; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy* / Q000473:pathology*; D011241:Prednisone / Q000008:administration & dosage; D000069283:Rituximab; D015996:Survival Rate; D014750:Vincristine / Q000008:administration & dosage
D058846:Antibodies, Monoclonal, Murine-Derived; D000069283:Rituximab; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone