Nuclear Survivin Expression in Mantle Cell Lymphoma Is Associated with Cell Proliferation and Survival

Martı́nez, Antonio; Bellosillo, Beatríz; Bosch, Francesc; Ferrer, Ana; Marcé, Sílvia; Villamor, Neus; Ott, German; Montserrat, Emili; Campo, Elı́as; Colomer, Dolors

doi:10.1016/s0002-9440(10)63140-9

Cited by 92 publications

(78 citation statements)

References 48 publications

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“…Survivin is a cytoplasmic protein, and the nuclear localization is required for its function in the proliferation and apoptosis regulation [32][33][34]. In the present study, we showed that LMP1 could promote Survivin to accumulate in the nuclei and bind with CDK4.…”

Section: Initiation Of Survivin/ Cdk4 Complex Formation In the Nucleisupporting

confidence: 49%

Regulation of Survivin and CDK4 by Epstein-Barr virus encoded latent membrane protein 1 in nasopharyngeal carcinoma cell lines

Zhao

et al. 2005

Cell Res

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Latent membrane protein 1 (LMP1), an important protein encoded by Epstein Barr virus (EBV), has been implied to link with the pathogenesis of nasopharyngeal carcinoma (NPC). Its dual effects of increasing cell proliferation and inhibiting cell apoptosis have been confirmed. In this study, we showed that the expression of Survivin and CDK4 protein in CNE-LMP1, a LMP1 positive NPC epithelial cell line, is higher than in LMP1 negative NPC epithelial cell line-CNE1, and the expression is LMP1 dosage-dependent. Although it was reported that Survivin specifically expressed in cell cycle G 2 /M phase, our studies suggested that LMP1 could promote the expression of Survivin in G 0 /G 1 , S and G 2 / M phase. It also showed that Survivin and CDK4 could be accumulated more in the nuclei triggered by LMP1. More interestingly, Survivin and CDK4 could form a protein complex in the nuclei of CNE-LMP1 rather than in that of CNE1, which demonstrated that the interaction between these two proteins could be promoted by LMP1. These results strongly suggested that the role of LMP1 in the regulation of Survivin and CDK4 may also shed some light on the mechanism research of LMP1 in NPC.

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Section: Initiation Of Survivin/ Cdk4 Complex Formation In the Nucleisupporting

confidence: 49%

Regulation of Survivin and CDK4 by Epstein-Barr virus encoded latent membrane protein 1 in nasopharyngeal carcinoma cell lines

Zhao

et al. 2005

Cell Res

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“…Finally, in two recent papers, nuclear Survivin overexpression has been associated with poor prognosis in mantle cell lymphoma (Martinez et al, 2004) and oesophageal squamous cell carcinoma (Grabowski et al, 2003). The results of these studies contributed to the confusion regarding the role of nuclear expression of Survivin.…”

Section: Discussionmentioning

confidence: 99%

Nuclear and cytoplasmic expression of survivin in 67 surgically resected pancreatic cancer patients

et al. 2005

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Pancreatic cancer is one of the most aggressive gastrointestinal cancer with less than 10% long-term survivors. The apoptotic pathway deregulation is a postulated mechanism of carcinogenesis of this tumour. The present study investigated the prognostic role of apoptosis and apoptosis-involved proteins in a series of surgically resected pancreatic cancer patients. All patients affected by pancreatic adenocarcinoma and treated with surgical resection from 1988 to 2003 were considered for the study. Patients' clinical data and pathological tumour features were recorded. Survivin and Cox-2 expression were evaluated by immunohistochemical staining. Apoptotic cells were identified using the TUNEL method. Tumour specimen of 67 resected patients was included in the study. By univariate analysis, survival was influenced by Survivin overexpression. The nuclear Survivin overexpression was associated with better prognosis (P ¼ 0.0009), while its cytoplasmic overexpression resulted a negative prognostic factor (P ¼ 0.0127). Also, the apoptotic index was a statistically significant prognostic factor in a univariate model (P ¼ 0.0142). By a multivariate Cox regression analysis, both the nuclear (P ¼ 0.002) and cytoplasmic (P ¼ 0.040) Survivin overexpression maintained the prognostic statistical value. This is the first study reporting a statistical significant prognostic relevance of nuclear and cytoplasmic Survivin overexpression in pancreatic cancer. In particular, patients with high nuclear Survivin staining showed a longer survival, whereas patients with high cytoplasmic Survivin staining had a shorter overall survival.

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“…Different prognostic significance of BIRC5 nuclear labeling in several tumor types has been reported in recent years, [45][46][47][48][49][50] as summarized in reference Li et al 51 For example, correlation of BIRC5 nuclear (but not cytoplasmic) staining with poor prognosis has been reported in ependymoma, esophageal squamous cell carcinoma, hepatocellular carcinoma, mantel cell lymphoma, and non-small cell lung cancer. [45][46][47][48] Paradoxically, BIRC5 nuclear staining was reported to be associated with better prognosis in gastric cancer and breast cancer.…”

Section: Discussionmentioning

confidence: 99%

“…[45][46][47][48] Paradoxically, BIRC5 nuclear staining was reported to be associated with better prognosis in gastric cancer and breast cancer. 49,50 It has been proposed that variations in immunostaining and interpretation might be among the contributing factors to these conflicting results.…”

Section: Discussionmentioning

confidence: 99%

Survivin nuclear labeling index: a superior biomarker in superficial urothelial carcinoma of human urinary bladder

Chen

Zhang

et al. 2006

Modern Pathology

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The caspase family proteases are key proapoptotic proteins while the inhibitor of apoptosis proteins (IAP) prevent apoptosis by antagonizing the caspases or other key proapoptotic proteins. Limited studies of IAPs suggested their deregulation contributed to urothelial neoplasia. However, the expression status and biologic or prognostic significance of the caspase and IAP family proteins in urothelial neoplasms is not clear. In the present study, we first systematically evaluated the expression profile of the major apoptosis regulators, including caspases (CASP3,6,7,8,9,10,and 14), IAPs (survivin/BIRC5, CIAP1, CIAP2, XIAP, and LIVIN), APAF1, SMAC, and BCL2, as well as proliferation markers Ki67 and PHH3, in Ta/T1 human urinary bladder urothelial carcinomas and normal urothelium samples by immunohistochemistry. The analysis showed that survivin/ BIRC5 nuclear labeling index (BIRC5-N), but not cytoplasmic staining, was the only apoptotic marker which correlated significantly with tumor grade, stage, and patient outcome. We further analyzed the prognostic value of BIRC5-N in 101 Ta/T1 urinary bladder urothelial carcinomas by univariate analysis, which showed that BIRC5-N as well as the more classical prognosticators (stage, grade, and Ki67 index) were of prognostic significance. However, multivariate analysis by Cox proportional hazard regression demonstrated BIRC5-N was a stronger prognosticator than tumor grade, stage, and Ki67 labeling index. BIRC5-N index of 8% or more predicted unfavorable disease-specific survival (relative risk (RR) ¼ 6.6, 95% confidence interval ¼ 1.6-26.7, P ¼ 0.0080) as well as progression-free survival (RR ¼ 4.4, 95% confidence interval ¼ 1.3-14.6, P ¼ 0.0151). We conclude that BIRC5-N is a superior biologic and prognostic marker for Ta/T1 urothelial carcinomas of urinary bladder.

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Nuclear Survivin Expression in Mantle Cell Lymphoma Is Associated with Cell Proliferation and Survival

Cited by 92 publications

References 48 publications

Regulation of Survivin and CDK4 by Epstein-Barr virus encoded latent membrane protein 1 in nasopharyngeal carcinoma cell lines

Regulation of Survivin and CDK4 by Epstein-Barr virus encoded latent membrane protein 1 in nasopharyngeal carcinoma cell lines

Nuclear and cytoplasmic expression of survivin in 67 surgically resected pancreatic cancer patients

Survivin nuclear labeling index: a superior biomarker in superficial urothelial carcinoma of human urinary bladder

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