Survivin expression in tumor cell nuclei is predictive of a favorable prognosis in gastric cancer patients

Okada, Eikichi; Murai, Yoshihiro; Matsui, Kazuhiro; Isizawa, Shin; Cheng, Chunmei; Masuda, Mitsunobu; Takano, Yasuo

doi:10.1016/s0304-3835(00)00677-7

Cited by 154 publications

(125 citation statements)

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“…This implies, functionally, that the selective loss of expression of the nuclear form of Survivin may play a role in tumour progression or anaplasia. These data are consistent with that of recent publications of Survivin expression in breast and gastric carcinomas, which demonstrated that lower nuclear expression of Survivin was an independent prognostic indicator of poor prognosis (Okada et al, 2001;Kennedy et al, 2003). As the number of cases in our study was not large enough to assess the impact of nuclear Survivin staining as an independent prognostic factor in this subset of brain tumours, we cannot defend its use as a marker for clinical outcome at this time.…”

Section: Discussionsupporting

confidence: 90%

“…These have included vascular endothelial cells, colonic epithelium, normal endometrium, and lymphocytes (Konno et al, 2000;Gianani et al, 2001;Fukuda et al, 2002;Altieri, 2003). In addition, other investigators have shown that expression of the nuclear form of Survivin in breast and gastric carcinomas is an independent prognostic indicator of good prognosis in these tumours, suggesting that a loss of nuclear Survivin expression may play a role in tumour progression (Okada et al, 2001;Kennedy et al, 2003).…”

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confidence: 99%

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Nuclear expression of Survivin in paediatric ependymomas and choroid plexus tumours correlates with morphologic tumour grade

et al. 2003

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Section: Discussionsupporting

confidence: 90%

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confidence: 99%

Nuclear expression of Survivin in paediatric ependymomas and choroid plexus tumours correlates with morphologic tumour grade

et al. 2003

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“…Our data seem to go against the original hypothesis that survivin might predict a more aggressive clinical outcome, although some evidences have been reported documenting the absence of any association between survivin expression and prognosis in some solid tumours (Grabowski et al, 2003;Li, 2003), and even a favourable prognostic role of high nuclear survivin content in gastric and bladder tumours (Okada et al, 2001;Lehner et al, 2002). The possibility that the biological and clinical role of survivin expression might also be influenced by tissue specificity cannot be ruled out and deserves further attention.…”

Section: Discussioncontrasting

confidence: 81%

Survivin expression in ovarian cancer and its correlation with clinico-pathological, surgical and apoptosis-related parameters

et al. 2005

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We investigated the association of survivin expression with prognosis and other apoptosis-related biological factors in 110 primary ovarian cancer patients admitted to the Division of Gynecologic Oncology, Catholic University of Rome. Immunohistochemistry was performed on formalin-fixed, paraffin-embedded sections by using polyclonal antibody ab469 for survivin, and mouse monoclonal antibodies (clone 124 and DO-7), for bcl-2 and p53, respectively. Cytoplasmic survivin immunoreaction was observed in 84.5% cases, while nuclear survivin immunostaining was observed in 29.1% cases. We failed to find any relationship between cytoplasmic survivin positivity rate and any of the parameters examined. Serous tumours showed a lower percentage of nuclear survivin positivity with respect to other histotypes (20.5 vs 48.6%, respectively; P-value ¼ 0.004). The percentage of nuclear survivin positivity was higher in cases subjected to primary tumour cytoreduction (43.5%), with respect to patients subjected to exploratory laparotomy (20%) (P ¼ 0.024). Bcl-2 and p53 were, respectively, expressed in 27.3 and 60.0% of the cases and their expression was not correlated with survivin status. During the follow-up period, progression and death of disease were observed in 68 (61.8%) and 53 (48.2%) cases, respectively. There was no difference in time to progression and overall survival according to survivin status in ovarian cancer patients. In conclusion, in our experience, the immunohistochemical assessment of survivin status does not seem to be helpful in the prognostic characterisation of ovarian cancer. A more in depth investigation of the complex physiology of divergent survivin variants is needed in order to clarify the biological and the clinical role of differentially located survivin isoforms. (Hoskins et al, 2000), it is conceivable that the assessment of biochemical factors more strictly related to tumour cell biology and intrinsic aggressiveness could help identifying high-risk patients and facilitating management of this disease.Apoptosis (programmed cell death) has been proposed to play a role not only in cancer onset and progression but also in sustaining decreased tumour cell sensitivity to chemotherapy (Hickman, 1992;Thompson, 1995), which still represents one of the main prognostic indicators in this neoplasia (Hoskins et al, 2000). In this context, the analysis of the molecules possibly involved in the modulation of apoptosis seems to be particularly attractive.Survivin is a member of the inhibitors of apoptosis protein (IAP) family, which participates in the complex network regulating programmed cell death and also cell division (Ambrosini et al, 1997;Altieri and Marchisio, 1999;Salvesen and Duckett, 2002). Survivin protein is commonly detected in fetal tissues but not in normal adult tissues, while being overexpressed in human cancer, thus suggesting the contribution of survivin gene reactivation in carcinogenesis (Ambrosini et al, 1997). The crucial role of survivin in protection from apoptosis is supported by the o...

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“…Interestingly, nuclear Survivin localisation in gastric (Okada et al, 2001) and transitional cell carcinoma (Lehner et al, 2002) is considered predictive of a favourable prognosis. Recently, Survivin has been detected in the nucleus of non-smallcell lung cancer cells from clinical samples, without any significant relation with clinical outcome (Falleni et al, 2003).…”

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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Survivin expression in tumor cell nuclei is predictive of a favorable prognosis in gastric cancer patients

Cited by 154 publications

References 16 publications

Nuclear expression of Survivin in paediatric ependymomas and choroid plexus tumours correlates with morphologic tumour grade

Nuclear expression of Survivin in paediatric ependymomas and choroid plexus tumours correlates with morphologic tumour grade

Survivin expression in ovarian cancer and its correlation with clinico-pathological, surgical and apoptosis-related parameters

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

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