TY - JOUR
T1 - Prognostic and biological significance of survivin expression in patients with diffuse large B-cell lymphoma treated with rituximab-CHOP therapy
AU - Liu, Zhiyu
AU - Xu-Monette, Zijun Y.
AU - Cao, Xin
AU - Manyam, Ganiraju C.
AU - Wang, Xiaoxiao
AU - Tzankov, Alexandar
AU - Xia, Yi
AU - Li, Xin
AU - Visco, Carlo
AU - Sun, Ruifang
AU - Zhang, Li
AU - Montes-Moreno, Santiago
AU - Dybkær, Karen
AU - Chiu, April
AU - Orazi, Attilio
AU - Zu, Youli
AU - Bhagat, Govind
AU - Richards, Kristy L.
AU - Hsi, Eric D.
AU - Choi, William W.L.
AU - Van Krieken, J. Han
AU - Huh, Jooryung
AU - Ponzoni, Maurilio
AU - Ferreri, Andrés J.M.
AU - Parsons, Ben M.
AU - Møller, Michael B.
AU - Piris, Miguel A.
AU - Winter, Jane N.
AU - O'Malley, Dennis P.
AU - Medeiros, L. Jeffrey
AU - Young, Ken H.
N1 - Funding Information:
This study was supported by the National Cancer Institute/National Institutes of Health (R01CA138688 and 1RC1CA146299 to KHY). ZL is the recipient of a scholarship research award; GCM is supported by a grant from the Michael and Susan Dell Foundation; ZYX-M is the recipient of the Harold C and Mary L. Daily Endowment Fellowship and the Shannon Timmins Fellowship for Leukemia Research Award. KHY is supported by The University of Texas MD Anderson Cancer Center Institutional Research and Development Fund, an Institutional Research Grant Award, an MD Anderson Cancer Center Lymphoma Specialized Programs on Research Excellence (SPORE) Research Development Program Award, an MD Anderson Cancer Center Myeloma SPORE Research Development Program Award, a Gundersen Lutheran Medical Foundation Award, and MD Anderson Cancer Center Collaborative Funds with Roche Molecular System, Gilead Pharmaceutical, Dai Sanyo Pharmaceutical, Adaptive Biotechnology, and HTG Molecular Diagnostics, and partially supported by the National Cancer Institute/National Institutes of Health (P50CA136411 and P50CA142509). This work was also partially supported by National Cancer Institute and National Institutes of Health grants P50CA136411 and P50CA142509, and by MD Anderson’s Cancer Center Support Grant CA016672.
Publisher Copyright:
© 2015 USCAP, Inc All rights reserved.
Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 2015/10/3
Y1 - 2015/10/3
N2 - Survivin, a member of the inhibitor of apoptosis protein family, is overexpressed in a variety of human neoplasms. The prognostic significance of survivin expression in diffuse large B-cell lymphoma patients treated with rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) is unclear. We used standard immunohistochemistry methods to quantify survivin expression in 463 patients with de novo diffuse large B-cell lymphoma who received the R-CHOP. Of the 463 patients, 269 (58%) had survivin overexpression with a cutoff of >25%, associated with an International Prognostic Index score of >2 (P=0.015), disease in ≥2 extranodal sites (P=0.011), and a high Ki-67 index (P<0.0001). Among patients with activated B cell-like disease, the overall survival rate of survivin-positive patients was significantly lower than that of survivin-negative patients (P=0.033); multivariate analysis confirmed that in these patients, survivin overexpression was an independent prognostic factor for survival. Among patients with wild-type p53 overexpression, the overall survival and progression-free survival rates of the survivin-positive group were significantly lower than those of the survivin-negative group (P=0.035 and P=0.04 respectively). In STAT3-positive patients, survivin overexpression was associated with significantly better survival. Among patients with activated B cell-like disease, survivin-positive compared with survivin-negative groups had significantly different gene expression signatures, including genes involved in mitosis or tumor cell proliferation. Our results indicate that survivin is an independent prognostic factor for poor outcome in patients with activated B cell-like disease treated with the R-CHOP regimen, and patients with survivin-positive activated B cell-like diffuse large B-cell lymphoma seem to benefit less from this treatment and may require additional novel agents.
AB - Survivin, a member of the inhibitor of apoptosis protein family, is overexpressed in a variety of human neoplasms. The prognostic significance of survivin expression in diffuse large B-cell lymphoma patients treated with rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) is unclear. We used standard immunohistochemistry methods to quantify survivin expression in 463 patients with de novo diffuse large B-cell lymphoma who received the R-CHOP. Of the 463 patients, 269 (58%) had survivin overexpression with a cutoff of >25%, associated with an International Prognostic Index score of >2 (P=0.015), disease in ≥2 extranodal sites (P=0.011), and a high Ki-67 index (P<0.0001). Among patients with activated B cell-like disease, the overall survival rate of survivin-positive patients was significantly lower than that of survivin-negative patients (P=0.033); multivariate analysis confirmed that in these patients, survivin overexpression was an independent prognostic factor for survival. Among patients with wild-type p53 overexpression, the overall survival and progression-free survival rates of the survivin-positive group were significantly lower than those of the survivin-negative group (P=0.035 and P=0.04 respectively). In STAT3-positive patients, survivin overexpression was associated with significantly better survival. Among patients with activated B cell-like disease, survivin-positive compared with survivin-negative groups had significantly different gene expression signatures, including genes involved in mitosis or tumor cell proliferation. Our results indicate that survivin is an independent prognostic factor for poor outcome in patients with activated B cell-like disease treated with the R-CHOP regimen, and patients with survivin-positive activated B cell-like diffuse large B-cell lymphoma seem to benefit less from this treatment and may require additional novel agents.
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U2 - 10.1038/modpathol.2015.94
DO - 10.1038/modpathol.2015.94
M3 - Article
C2 - 26248897
AN - SCOPUS:84942987649
VL - 28
SP - 1297
EP - 1314
JO - Modern Pathology
JF - Modern Pathology
SN - 0893-3952
IS - 10
ER -