High expression levels of survivin protein independently predict a poor outcome for patients who undergo surgery for clear cell renal cell carcinoma

Department of Urology, Mayo Clinic College of Medicine, Jacksonville, Florida, USA.
Cancer (Impact Factor: 4.89). 07/2006; 107(1):37-45. DOI: 10.1002/cncr.21952
Source: PubMed


In a previous study of gene array data, the authors identified survivin as a candidate marker of aggressiveness in clear cell renal cell carcinoma (ccRCC). What remained in question was whether survivin expression at the protein level is an independent predictor of disease progression and cancer-specific survival.
Between 1990 and 1994, 312 patients underwent nephrectomy for ccRCC at Mayo Clinic Rochester and had paraffin tissue available. The authors performed immunohistochemistry with antisurvivin antibody, quantitated the expression by using an image-analysis system, and analyzed the association of survivin expression with disease progression and cancer-specific survival.
Within the cohort, 97 patients (31.1%) had high levels of survivin expression. Patients who had high survivin expression levels were at significantly increased risk of death from RCC compared with patients who had low expression levels (risk ratio [RR], 5.3; 95% confidence interval [95% CI], 3.5-7.9). The 5-year cancer-specific survival rate was 43.0% for patients with high survivin expression and 87.2% for patients with low survivin expression. In multivariate analysis, survivin expression remained associated with death from RCC even after adjusting for the Eastern Cooperative Oncology Group performance status; 2002 Tumor, Lymph Node, Metastases (TNM) stage groupings and nuclear grade (RR, 2.4; 95%CI, 1.5-3.8); and the Mayo Clinic composite TNM stage groupings, tumor size, nuclear grade, and tumor necrosis (SSIGN) score (RR, 1.8; 95%CI, 1.1-2.9). Among 273 patients who had localized ccRCC, survivin expression was associated significantly with cancer progression (RR, 3.9; 95%CI, 2.4-6.2).
Survivin expression is an independent predictor of ccRCC progression and death from RCC. Thus, survivin has the potential to offer additional prognostic information and to provide a novel target for the development of new adjuvant therapies.

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Available from: Bradley C Leibovich, Sep 09, 2014
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    • "Patients harbouring tumours with methylated APAF1, another apoptotic marker, had a greater risk of recurrence and disease-specific death from RCC [53] [54]. Increased survivin expression, another inhibitor of apoptosis, has also been independently associated with higher stage and grade and lower disease-specific survival from RCC [55] [56] [57] [58]. A recent study showed that mTOR activation of pS6K increases protein levels of survivin, which blocks extrinsic and intrinsic apoptotic pathways, showing the role of mTOR in cell survival [59]. "
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    ABSTRACT: Objectives Increased knowledge about the molecular pathways involved in tumorigenesis has led to the discovery of new prognostic molecular markers and development of novel targeted therapies for renal cell carcinoma (RCC). In this review we describe the prognostic markers of RCC and highlight the areas of recent discovery with a focus on the mammalian target of rapamycin (mTOR) pathway.Methods We reviewed previous reports, using PubMed with the search terms ‘renal cell carcinoma’, ‘molecular markers’, ‘prognosis’, ‘outcomes’ and ‘mammalian target of rapamycin pathway’ published in the last two decades. We created a library of 100 references and focused on presenting the recent advances in the field.ResultsGrowing evidence suggests that mTOR deregulation is associated with many types of human cancer, including RCC. Consequently, temsirolimus and everolimus, which target mTOR, are approved for treating advanced RCC. There is a demand to integrate clinical, pathological and molecular markers into accurate prognostic models to provide patients with the most personalised cancer care possible.Conclusions The mTOR pathway is highly implicated in RCC tumorigenesis and progression, and its constituents might represent a promising prognostic tool and target for treating RCC. Combining newly discovered molecular markers with classic clinicopathological prognostics might potentially improve the management of RCC.
    Full-text · Article · Jun 2012 · Arab Journal of Urology
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    • "Survivin expression has been correlated with several adverse pathological features of clear cell RCC, including tumor size, nuclear grade, TNM classification, presence of metastatic disease, coagulative tumor necrosis, and sarcomatoid differentiation [16]. Moreover, in a series reported by Parker et al, 312 patients with high survivin expression were twice as likely to die from clear cell RCC as were patients with low survivin expression [16]. "
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    ABSTRACT: The diagnosis of clinically early-stage (T1) renal cell carcinoma (RCC) has increased. The present study evaluated the association of B7-H4 expression on the pathological outcome and recurrence of carcinoma in the T1 stage of RCC. Among patients who underwent partial or radical nephrectomy after diagnosis of T1 stage RCC during the period of January 2000 to March 2007, 102 pathologically confirmed cases of clear cell carcinoma were included in this study. The patients' medical records were reviewed retrospectively. For the immunohistochemical staining tests, the B7-H4 antibody (Abbiotec 1:500) was used, and clinicopathological characteristics were analyzed. The mean age of the patients (39 males: 38.2%, 63 females: 61.8%) was 53.0±12.0 years (range, 31-74 years), and the mean follow-up time was 33.4±21.0 months (range, 6-84 months). B7-H4 expression was positive in 18 cases and negative in 84 cases. Recurrence during the follow-up period occurred in 5 cases in the group with positive B7-H4 expression and in 7 cases in the group with negative B7-H4 expression, respectively (p=0.035). In the univariate analysis, a statistically significant relationship was observed only for the presence of B7-H4 expression (p=0.0019). In the multivariate analysis, other than the expression of B7-H4, cancer size and TNM stage had effects on the recurrence of cancer. For clear cell RCC, B7-H4 expression had a critical impact on the prognosis of the patients, particularly on the recurrence of the carcinoma in patients with clinical stage T1 RCC.
    Full-text · Article · Feb 2011 · Korean journal of urology
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    • "Survivin is an antiapoptotic protein that belongs to the inhibitor of apoptosis protein family [14]. It has been shown that survivin expression is an independent predictor of ccRCC pregression and death [15]. In tissue, survivin can be reliably detected by means of immunohistochemistry. Automated evaluation of survivin expression might portend valuable information on ccRCC biology. "
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    ABSTRACT: As medical image data sets are digitized and the number of data sets is increasing exponentially, there is a need for automated image processing and analysis technique. Most medical imaging methods require human visual inspection and manual measurement which are labor intensive and often produce inconsistent results. In this paper, we propose an automated image segmentation and classification method that identifies tumor cell nuclei in medical images and classifies these nuclei into two categories, stained and unstained tumor cell nuclei. The proposed method segments and labels individual tumor cell nuclei, separates nuclei clusters, and produces stained and unstained tumor cell nuclei counts. The representative fields of view have been chosen by a pathologist from a known diagnosis (clear cell renal cell carcinoma), and the automated results are compared with the hand-counted results by a pathologist.
    Preview · Article · Feb 2009 · Proceedings of SPIE - The International Society for Optical Engineering
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