Prognostic and biological significance of survivin expression in patients with diffuse large B-cell lymphoma treated with rituximab-CHOP therapy Journal Article
| Authors: | 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.; Choi, W. W. L.; van Krieken, J. H.; Huh, J.; Ponzoni, M.; Ferreri, A. J. M.; Parsons, B. M.; Møller, M. B.; Piris, M. A.; Winter, J. N.; O'Malley, D. P.; Medeiros, L. J.; Young, K. H. |
| Article Title: | 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 >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. © 2015 USCAP, Inc All rights reserved. |
| Keywords: | immunohistochemistry; signal transduction; protein kinase b; adolescent; adult; cancer survival; controlled study; human tissue; protein expression; treatment outcome; treatment response; aged; unclassified drug; gene mutation; overall survival; prednisone; clinical feature; disease course; cancer localization; doxorubicin; cancer combination chemotherapy; cancer growth; comparative study; rituximab; cancer staging; follow up; dna replication; ki 67 antigen; cell proliferation; mitosis; protein analysis; gene overexpression; protein bcl 2; stat3 protein; progression free survival; gene expression profiling; protein; genetic association; cyclophosphamide; vincristine; genetic transcription; protein p53; survivin; b lymphocyte induced maturation protein 1; disease severity; dna; messenger rna; histone; myc protein; cancer size; rna translation; lactate dehydrogenase; upregulation; large cell lymphoma; cell cycle regulation; lactate dehydrogenase blood level; rad51 protein; dna topoisomerase; international prognostic index; translation regulation; cancer prognosis; human; male; female; priority journal; article; cep55 protein; histone h2afx; histone h2afz; taf5 protein; topoisomerase 2a; tripartite motif protein 35; b cell like diffuse large b cell lymphoma |
| Journal Title: | Modern Pathology |
| Volume: | 28 |
| Issue: | 10 |
| ISSN: | 0893-3952 |
| Publisher: | Nature Research |
| Date Published: | 2015-10-01 |
| Start Page: | 1297 |
| End Page: | 1314 |
| Language: | English |
| DOI: | 10.1038/modpathol.2015.94 |
| PROVIDER: | scopus |
| PUBMED: | 26248897 |
| DOI/URL: | |
| Notes: | Export Date: 2 November 2015 -- Source: Scopus |
