Prognostic impact of immunohistochemical biomarkers in diffuse large B-cell lymphoma in the rituximab era.
We evaluated the usefulness of prognostic markers in patients with diffuse large B-cell lymphoma (DLBCL) treated with cyclophosphamide, vincristine, doxorubicin, and prednisolone (CHOP) +/- rituximab (R-CHOP) in Japan. We studied 730 patients with DLBCL; 451 received CHOP and 279 R-CHOP. We analyzed biopsy samples immunohistochemically for markers of germinal center B cells (CD10, Bcl-6), postgerminal center B cells (Multiple myeloma-1), and apoptosis (Bcl-2). The median follow-up period for surviving patients was 56.4 months for the CHOP group and 25.2 months for the R-CHOP group. DLBCL were categorized as germinal center B (GCB) subtype (352/730; 48.2%) or non-GCB subtype (378/730; 51.8%). In the CHOP group, the high expression of CD10 (P = 0.022) or Bcl-6 (P = 0.021), or GCB subtype (P = 0.05) was associated with better overall survival, whereas the high expression of Bcl-2 (P = 0.001) or MUM1 (P = 0.011), or non-GCB subtype (P = 0.05) was associated with worse overall survival. In the R-CHOP group, however, these biomarkers except Bcl-6 were not significant prognostic factors. The patients with non-GCB subtype showed improved survival in the R-CHOP group (P = 0.756). The International Prognostic Index was a useful clinical marker of survival in the CHOP group (P < 0.001) and also in the R-CHOP group (P < 0.001). Results of improved survival with rituximab addition indicate that the relevance of previously recognized prognostic factors should be re-evaluated.
Seki
Ritsuko
R
Division of Hematology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan.
Ohshima
Koichi
K
Fujisaki
Tomoaki
T
Uike
Naokuni
N
Kawano
Fumio
F
Gondo
Hisashi
H
Makino
Shigeyoshi
S
Eto
Tetsuya
T
Moriuchi
Yukiyoshi
Y
Taguchi
Fumihiro
F
Kamimura
Tomohiko
T
Tsuda
Hiroyuki
H
Ogawa
Ryosuke
R
Shimoda
Kazuya
K
Yamashita
Kiyoshi
K
Suzuki
Keiko
K
Suzushima
Hitoshi
H
Tsukazaki
Kunihiro
K
Higuchi
Masakazu
M
Utsunomiya
Atae
A
Iwahashi
Masahiro
M
Imamura
Yutaka
Y
Tamura
Kazuo
K
Suzumiya
Junji
J
Yoshida
Minoru
M
Abe
Yasunobu
Y
Matsumoto
Tadashi
T
Okamura
Takashi
T
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D058846:Antibodies, Monoclonal, Murine-Derived; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D014408:Biomarkers, Tumor / Q000032:analysis*; D003520:Cyclophosphamide / Q000008:administration & dosage; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics; D004317:Doxorubicin / Q000008:administration & dosage; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D050835:Interferon Regulatory Factors / Q000096:biosynthesis / Q000235:genetics; D053208:Kaplan-Meier Estimate; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D015260:Neprilysin / Q000096:biosynthesis / Q000235:genetics; D011241:Prednisone / Q000008:administration & dosage; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis / Q000235:genetics; D051560:Proto-Oncogene Proteins c-bcl-6; D000069283:Rituximab; D014750:Vincristine / Q000008:administration & dosage; D000099218:Interferon Regulatory Factor-4
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D014408:Biomarkers, Tumor; D003520:Cyclophosphamide; D004268:DNA-Binding Proteins; D004317:Doxorubicin; D050835:Interferon Regulatory Factors; D015260:Neprilysin; D011241:Prednisone; D019253:Proto-Oncogene Proteins c-bcl-2; D051560:Proto-Oncogene Proteins c-bcl-6; D000069283:Rituximab; D014750:Vincristine; D000099218:Interferon Regulatory Factor-4; C084103:BCL6 protein, human