Prognostic and biological significance of survivin expression in patients with diffuse large B-cell lymphoma treated with rituximab-CHOP therapy

被引：20

作者：

Liu, Zhiyu ^{[1
]}

Xu-Monette, Zijun Y. ^{[1
]}

Cao, Xin ^{[1
]}

Manyam, Ganiraju C. ^{[2
]}

Wang, Xiaoxiao ^{[1
]}

Tzankov, Alexandar ^{[3
]}

Xia, Yi ^{[1
]}

Li, Xin ^{[1
]}

Visco, Carlo ^{[4
]}

Sun, Ruifang ^{[1
]}

Zhang, Li ^{[2
]}

Montes-Moreno, Santiago ^{[5
]}

Dybkaer, Karen ^{[6
]}

Chiu, April ^{[7
]}

Orazi, Attilio ^{[8
]}

Zu, Youli ^{[9
]}

Bhagat, Govind ^{[10
,11
]}

Richards, Kristy L. ^{[12
]}

Hsi, Eric D. ^{[13
]}

Choi, William W. L. ^{[14
]}

van Krieken, J. Han ^{[15
]}

Huh, Jooryung ^{[16
]}

Ponzoni, Maurilio ^{[17
]}

Ferreri, Andres J. M. ^{[17
]}

Parsons, Ben M. ^{[18
]}

Moller, Michael B. ^{[19
]}

Piris, Miguel A. ^{[5
]}

Winter, Jane N. ^{[20
]}

O'Malley, Dennis P. ^{[21
]}

Medeiros, L. Jeffrey ^{[1
]}

Young, Ken H. ^{[1
,22
]}

机构：

[1] Univ Texas MD Anderson Canc Ctr, Dept Hematopathol, Houston, TX 77030 USA

[2] Univ Texas MD Anderson Canc Ctr, Dept Bioinformat & Computat Biol, Houston, TX 77030 USA

[3] Univ Basel Hosp, CH-4031 Basel, Switzerland

[4] San Bortolo Hosp, Vicenza, Italy

[5] Hosp Univ Marques de Valdecilla, Santander, Spain

[6] Aalborg Univ Hosp, Aalborg, Denmark

[7] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA

[8] Cornell Univ, Weill Med Coll, New York, NY 10021 USA

[9] Houston Methodist Hosp, Houston, TX USA

[10] Columbia Univ, Med Ctr, New York, NY USA

[11] New York Presbyterian Hosp, New York, NY USA

[12] Univ N Carolina, Sch Med, Chapel Hill, NC USA

[13] Cleveland Clin, Cleveland, OH 44106 USA

[14] Univ Hong Kong, Li Ka Shing Fac Med, Hong Kong, Hong Kong, Peoples R China

[15] Radboud Univ Nijmegen, Med Ctr, NL-6525 ED Nijmegen, Netherlands

[16] Univ Ulsan, Coll Med, Asan Med Ctr, Seoul, South Korea

[17] Ist Sci San Raffaele, Milan, Italy

[18] Gundersen Lutheran Hlth Syst, La Crosse, WI USA

[19] Odense Univ Hosp, DK-5000 Odense, Denmark

[20] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA

[21] Clarient Pathol Serv, Aliso Viejo, CA USA

[22] Univ Texas Houston, Sch Med, Grad Sch Biomed Sci, Houston, TX USA

来源：

MODERN PATHOLOGY | 2015年 / 28卷 / 10期

基金：

美国国家卫生研究院;

关键词：

ANTI-APOPTOSIS GENE; CHEMOTHERAPY PLUS RITUXIMAB; CHROMOSOMAL PASSENGERS; YOUNG-PATIENTS; CANCER; INHIBITOR; PROTEIN; RISK; COMBINATION; SUPPRESSANT;

D O I：

10.1038/modpathol.2015.94

中图分类号：

R36 [病理学];

学科分类号：

100104 ;

摘要：

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.

引用

页码：1297 / 1314

页数：18

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