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

Zhiyu Liu, Zijun Y. Xu-Monette, Xin Cao, Ganiraju C. Manyam, Xiaoxiao Wang, Alexandar Tzankov, Yi Xia, Xin Li, Carlo Visco, Ruifang Sun, Li Zhang, Santiago Montes-Moreno, Karen Dybkær, April Chiu, Attilio Orazi, Youli Zu, Govind Bhagat, Kristy L. Richards, Eric D. Hsi, William W.L. ChoiJ. Han Van Krieken, Jooryung Huh, Maurilio Ponzoni, Andrés J.M. Ferreri, Ben M. Parsons, Michael B. Møller, Miguel A. Piris, Jane N. Winter, Dennis P. O'Malley, L. Jeffrey Medeiros, Ken H. Young*

*Corresponding author for this work

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1297-1314
Number of pages18
JournalModern Pathology
Volume28
Issue number10
DOIs
StatePublished - Oct 3 2015

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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    Liu, Z., Xu-Monette, Z. Y., Cao, X., Manyam, G. C., Wang, X., Tzankov, A., Xia, Y., Li, X., Visco, C., Sun, R., Zhang, L., Montes-Moreno, S., Dybkær, K., Chiu, A., Orazi, A., Zu, Y., Bhagat, G., Richards, K. L., Hsi, E. D., ... Young, K. H. (2015). Prognostic and biological significance of survivin expression in patients with diffuse large B-cell lymphoma treated with rituximab-CHOP therapy. Modern Pathology, 28(10), 1297-1314. https://doi.org/10.1038/modpathol.2015.94