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

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 425%, associated with an International Prognostic Index score of 42 (P = 0.015), disease in ≥ 2 extranodal sites (P = 0.011), and a high Ki-67 index (Po 0.0001). Among patients with activated B cell-like disease, the overall survival rate of survivin-positive patients was significantly lower than that of survivinnegative 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

Clinical impact of serum survivin positivity and tissue expression of EBV-encoded RNA in diffuse large B-cell lymphoma patients treated with rituximab-CHOP

“…Notably, subgroup analysis according to histological subtype suggested that serum survivin positivity had a more pronounced prognostic impact in patients with the non-GCB subtype DLBCL. These results are similar to those reported recently by Liu et al [18]. Considering the unmet need for additional effective treatment for ABC subtype DLBCL, these results suggests that survivin might be a useful prognostic marker and a therapeutic target in ABC subtype DLBCL.…”

“…Liu et al recently reported similar results that survivin expression was associated with a higher IPI risk score, higher number of extranodal disease, and higher Ki-67 index [18]. Meta-analysis also showed that positive survivin expression was associated with inferior OS and there was a significant association between survivin expression and advanced clinical stage (III and IV), higher IPI score (3–5), elevated serum LDH, presence of bone marrow involvement [19].…”

“…The first is the scarcity of data for uniformly R-CHOP-treated DLBCL populations. Many of the previous studies included DLBCL patients who were treated with mainly a CHOP regimen, except for the notable recent data published by Liu et al about the International Diffuse Large B-cell Lymphoma Rituximab-CHOP Consortium Program [18]. The second pitfall is the absence of uniform criteria for defining survivin expression positivity using immunohistochemistry.…”

Induction of autophagy and autophagy‐dependent apoptosis in diffuse large B‐cell lymphoma by a new antimalarial artemisinin derivative, SM1044

“…However, IPI only includes clinical parameters, and not biological indicators. Accumulating evidence suggests that molecular markers, such as high expression of Survivin, could be associated with poor prognosis DLBCL cases .…”

Clinical features, tumor biology, and prognosis associated with MYC rearrangement and Myc overexpression in diffuse large B-cell lymphoma patients treated with rituximab-CHOP

“…BCL6 and BCL2 translocations and TP53 mutations were detected as described previously. 15,21,24,[35][36][37][38][39][40][41][42] Gene Expression Profiling Gene expression profiling for 457 patients was performed using the Affymetrix GeneChip Human Genome HG-U133 Plus 2.0 Array as described previously. 21,24,[35][36][37] The CEL files have been deposited in the National Center for Biotechnology Information Gene Expression Omnibus repository (GSE31312).…”