Bcl-2 but not FOXP1, is an adverse risk factor in immunochemotherapy-treated non-germinal center diffuse large B-cell lymphomas.
OBJECTIVE
Non-germinal center (non-GC) phenotype, high level expression of the transcription factor forkhead box protein P1 (FOXP1) and anti-apoptotic protein Bcl-2 have been identified as unfavorable prognostic factors for diffuse large B-cell lymphoma (DLBCL) patients treated with chemotherapy. Our aim was to re-evaluate the prognostic impact of these biologic factors on the survival of the patients treated with immunochemotherapy.


METHODS
Expression of Bcl-2 and FOXP1, and cell of origin based on the Hans algorithm were determined immunohistochemically from samples of 117 de novo DLBCL patients treated with R-CHOP and R-CHOEP regimens, and correlated with clinical data.


RESULTS
Consistent with our previous studies, no significant difference in 2-yr survival rates between the GC- and non-GC phenotypes was found. Both FOXP1 and Bcl-2 expression were associated with the non-GC phenotype. For all patients, no prognostic impact of FOXP1 positivity on survival was observed. However, Bcl-2 negative patients had a better survival as compared to Bcl-2 positive patients [failure free survival (FFS) 97% vs. 71%, P = 0.001 and overall survival (OS) 97% vs. 82%, P = 0.034]. When Bcl-2 related survival was analyzed in the GC- and non-GC subgroups, a significant prognostic effect of Bcl-2 on FFS was seen only in the non-GC group of patients (positive 65% vs. negative 100%, P = 0.011). A trend for the difference in OS was also observed (positive 84% vs. negative 100%, P = 0.082).


CONCLUSIONS
The data demonstrate that expression of Bcl-2 and FOXP1 is associated with the non-GC phenotype, but only Bcl-2 expression continues to be of prognostic significance in DLBCL patients treated with immunochemotherapy.
Nyman
Heidi
H
Department of Oncology, Helsinki University Central Hospital, Helsinki, Finland.
Jerkeman
Mats
M
Karjalainen-Lindsberg
Marja-Liisa
ML
Banham
Alison H
AH
Enblad
Gunilla
G
Leppä
Sirpa
S
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D005260:Female; D051858:Forkhead Transcription Factors / Q000032:analysis*; D018858:Germinal Center; D006801:Humans; D007150:Immunohistochemistry; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy / Q000401:mortality* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis*; D012097:Repressor Proteins / Q000032:analysis*; D012189:Retrospective Studies; D012307:Risk Factors; D016019:Survival Analysis; D055815:Young Adult
C486626:FOXP1 protein, human; D051858:Forkhead Transcription Factors; D019253:Proto-Oncogene Proteins c-bcl-2; D012097:Repressor Proteins