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  • American Society of Clinical Oncology (ASCO)  (5)
  • 1
    Online Resource
    Online Resource
    Association of high cytoplasmic expression of p27 Kip1 on cancer-specific survival in clear cell renal cell carcinoma.
    American Society of Clinical Oncology (ASCO) ; 2012
    In:  Journal of Clinical Oncology Vol. 30, No. 5_suppl ( 2012-02-10), p. 418-418
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 30, No. 5_suppl ( 2012-02-10), p. 418-418
    Abstract: 418 Background: p27Kip1 is considered to contribute to the progression of ccRCC and is targeted by next generation dual-therapies. Cytoplasmic and nuclear differences of p27 Kip1 expression and localization in benign and clear cell renal cell carcinoma (ccRCC) were analyzed with regard to overall survival (OS) and cancer-specific survival (CSS). Methods: In 140 patients, ccRCC and corresponding benign kidney tissue were analyzed for nuclear and cytoplasmic staining of p27Kip1 by immunohistochemistry using a tissue microarray technique. Staining intensity and percentage of positive stained cells are given as expression scores. p27Kip1 expression was categorized as high if ccRCC tissue stained stronger than the respective level of the corresponding benign tissue and categorized as low if ccRCC tissue stained less than or equal to the corresponding benign tissue. Differences in OS and CSS were analyzed by log-rank analysis and expression levels were correlated with tumour and patient characteristics using Fisher’s exact test. Results: Cytoplasmatic (mean [SD]: 13.8% [1.2%] vs 10.7% [1.7%]; P = 0.04) and nuclear (mean [SD] : 75.6% [2.7%] vs 13.6% [2.1%] ; P 〈 0.001) staining of p27Kip1 were significantly stronger in ccRCC tissues compared to benign tissue. High cytoplasmic p27Kip1 expression was significantly associated with a higher T and N stage, Fuhrman grade and the presence of metastatic disease (P 〈 0.001). The median follow-up time was 38.2 months. There was no difference in OS between the low and high expression groups, although CSS was significantly lower in patients with high cytoplasmic p27Kip1 (P 〈 0.001) and CSS heavily tended to be lower in the nuclear low expression group (P = 0.069). Conclusions: High cytoplasmic p27Kip1 levels in renal cancer tissues are associated with advanced disease and reduced cancer specific survival, whereas low nuclear expression levels appear to be beneficial. The present study corroborates the consideration of cytoplasmic p27Kip1 for future diagnostic and targeted therapeutic approaches in RCC establishing a potential protective shift of p27Kip1 from the cytoplasm to the nucleus.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/jco.2012.30.5_suppl.418
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2012
    detail.hit.zdb_id: 2005181-5
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  • 2
    Online Resource
    Online Resource
    CpG island hypermethylation of corticotropin-releasing hormone-binding protein in kidney cancer and association with clinicopathological parameters.
    American Society of Clinical Oncology (ASCO) ; 2013
    In:  Journal of Clinical Oncology Vol. 31, No. 6_suppl ( 2013-02-20), p. 414-414
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 31, No. 6_suppl ( 2013-02-20), p. 414-414
    Abstract: 414 Background: Significance of Urocortin (Ucn or UcnI), Ucn2, Ucn3, and their receptors, Corticotropin Releasing Factor Receptor 1 and 2 (CRFR1 and CRFR2), and the binding protein, Corticotropin-Releasing Hormone-Binding Protein (CRHBP) in oncology is growing rapidly. Recently we found that the UCN system may also be a relevant structure in renal cell cancer. Here we investigate whether CRHBP CGI methylation occurs in cc-RCC and whether its methylation is associated with clinicopathological parameters of patients. Methods: Tumoral tissues of 109 patients with renal cell cancer and their corresponding normal tissues have been used. Combined bisulfite restriction analysis (COBRA) for detection of relative degree of CpG island (CGI) methylation and pyrosequencing have been performed. Results: We found an approximately five-fold increase in mean methylation of the CRHBP CGI for tumor tissues (p 〈 0.00005). Higher DNA methylation of the CRHBP CGI showed a positive correlation with advanced disease as well (p = 0.024). Conclusions: To our knowledge we report for the first time the CGI methylation of CRHBP in clear cell renal cell carcinoma indicating a contribution of epigenetic alteration of CRHBP to RCC tumorigenesis. Moreover, our results suggest CRHBP as a potential molecular marker for assessment of progression and aggressiveness of tumors.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/jco.2013.31.6_suppl.414
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2013
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
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  • 3
    Online Resource
    Online Resource
    Impact on clinical prognosis using DNA methylation of the SLC16A3 promoter and expression of the human lactate transporter MCT4 in renal cancer.
    American Society of Clinical Oncology (ASCO) ; 2014
    In:  Journal of Clinical Oncology Vol. 32, No. 4_suppl ( 2014-02-01), p. 452-452
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 32, No. 4_suppl ( 2014-02-01), p. 452-452
    Abstract: 452 Background: The monocarboxylate transporter 4 (MCT4) is a metabolic target in tumor biology because it mediates lactate transport across membranes resulting in antiapoptotic effects. Cell experiments support the importance of MCT4 in clear cell renal cell carcinoma (ccRCC). In this study, we assessed the prognostic potential of MCT4 expression in ccRCC and its epigenetic regulation by DNA methylation as novel predictive marker for patient outcome using independent ccRCC cohorts. Methods: MCT4 protein expression was quantified in 207 ccRCC and corresponding nontumor tissues. Data of an independent ccRCC cohort from The Cancer Genome Atlas (TCGA) were analyzed on MCT4 mRNA (n = 482) and DNA methylation (n = 283) level. The findings on MCT4 expression and DNA methylation in the SLC16A3 promoter were validated in a third cohort (n = 64). Promoter activity assays were conducted in four RCC cell lines. Results: MCT4 protein expression was upregulated (p 〈 0.0001) in ccRCC and showed significant association with cancer-related death. Upregulation of MCT4 mRNA expression (p 〈 0.00001) was confirmed in the TCGA cohort. Single CpG sites correlated inversely with mRNA expression and were associated with overall survival in Kaplan-Meier analyses [HR = 0.39; 95% confidence interval (CI), 0.24-0.64; P[log-rank] = 1.23e(-04)] . Promoter activity studies confirmed MCT4 regulation by DNA methylation. The significant correlation between MCT4 protein and gene expression or DNA methylation at single CpG sites was validated in a third cohort. Again, higher methylation at individual CpG sites was associated with prolonged survival [HR = 0.05; 95% CI, 0.01-0.40; P[log-rank] = 6.91e(-05)] . Conclusions: This study identified SLC16A3 promoter DNA methylation as a novel epigenetic mechanism for MCT4 regulation in ccRCC. First evidence of a biological rationale for prognosis and clinical outcome is supported by this specific SLC16A3 promoter DNA methylation.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/jco.2014.32.4_suppl.452
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2014
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
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  • 4
    Online Resource
    Online Resource
    Impact of altered Wnt1/ß-catenin expression on clinicopathology and prognosis in renal cell carcinoma.
    American Society of Clinical Oncology (ASCO) ; 2014
    In:  Journal of Clinical Oncology Vol. 32, No. 4_suppl ( 2014-02-01), p. 465-465
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 32, No. 4_suppl ( 2014-02-01), p. 465-465
    Abstract: 465 Background: Members of the Wnt/ß-catenin signaling pathway are abnormally expressed in renal cell carcinoma (RCC). This study analyzed the role of Wnt1/ß-catenin alterations in clear cell RCC (ccRCC) with regard to clinicopathology, overall survival (OS) and cancer specific survival (CSS) to prove the options of a Wnt targeted therapy. Methods: Corresponding ccRCCs and benign renal tissue were analyzed in 278 patients for Wnt1 and ß-catenin by immunohistochemistry in tissue microarrays. Expression scores including intensity and percentage of stained cells were compared between normal kidney and ccRCCs. Data was categorized according to the mean expressions core and correlated to tumor and patients’ characteristics and analyzed for OS and CSS according to the Kaplan-Meier and log-rank test. To identify prognostics value of wnt1 and ß-catenin, univariable and multivariable Cox proportional hazard regression models were used. Results: High Wnt1 tumor expression was associated with increased tumor diameter (p=0.01), stage (p=0.004) and vascular invasion (p=0.02). Positive membranous ß-catenin was associated with advanced stage (p=0.003), vascular invasion (p=0.01) and tumor necrosis (p=0.004). Increased tumor diameter (p=0.01), stage (p=0.003), node involvement (0.04), grade (p=0.001), vascular invasion (p=0.002), and sarcomatoid differentiation (p=0.01) were found in patients with high cytoplasmic ß-catenin. Furthermore, this patient subgroup showed reduced OS (p=0.03) and CSS (p=0.009). Conclusions: Significant clinicopathological associations underline the oncogenic potential of Wnt1/ß-catenin pathway parameters. Whereas, cytoplasmic ß-catenin was identified as the most valuable parameter with regard to clinico-prognostic implications for future targeted therapies.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/jco.2014.32.4_suppl.465
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2014
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
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  • 5
    Online Resource
    Online Resource
    Use of preoperative C-reactive protein to improve predictive accuracy in clear cell renal cell carcinoma.
    American Society of Clinical Oncology (ASCO) ; 2013
    In:  Journal of Clinical Oncology Vol. 31, No. 6_suppl ( 2013-02-20), p. 474-474
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 31, No. 6_suppl ( 2013-02-20), p. 474-474
    Abstract: 474 Background: White blood cell count (WBC) and C-reactive protein (CRP) are reliable biomarkers in clear cell renal cell carcinoma (ccRCC). Nevertheless, accepted cut-offs values for risk stratifications are missing. This study re-evaluated the prognostic and predictive significance of preoperatively WBC and CRP that independently predicts patient prognosis and to determine optimal cut-off values for CRP. Methods: 327 patients with surgery for ccRCC were retrospectively evaluated from 1996 to 2005. Cox-proportional hazard models were used, adjusted for the effects of tumor stage, tumor size, Fuhrman grade, and Karnofsky-Index; and to evaluate the prognostic significance of WBC and CRP; and to identify cut-off values. Identified cut-offs were correlated with clinico-pathological parameters and used to estimate cancer-specific survival (CSS). To prove any additional predictive accuracy of the identified cut-off it was compared to a clinico-pathological base model using Harrell c-index. Results: In univariable analyses WBC was a significant prognostic marker at a concentration of 9.5/µl (HR: 1.83) and 11.0/µl (HR: 2.09) and supported a CRP value of 0.25 mg/dL (HR: 6.47, p 〈 0.001) and 0.5mg/dL (HR: 7.15, p 〈 0.001) as potential cut-off values. If adjusted by the multivariable models WBC showed no clear breakpoint, but a CRP-value of 0.25mg/dL (HR: 2.80, p = 0.027) proved to be optimal. Reduced CSS was proven for CRP 0.25 mg/dL (median: 69.9 vs. 92.3 months). Median follow-up was 57.5 months with 72 (22%) tumor related deaths. The final model built by the addition of CRP 0.25mg/dL did not improve predictive accuracy (c-index = 0.877) than compared to the clinico-pathological base model (c-index =0.881) which included TNM-stage, grading and Karnofsky-Index. Conclusions: Multivariable analyses revealed an optimal breakpoint of CRP at a value of 0.25mg/dL best to stratify patients at risk of cancer-specific mortality, but CRP 0.25mg/dL added no additional information in the prediction model. Therefore we cannot recommend to measure CRP as the traditional parameters of TNM-stage, grading and Karnofsky-Index were already of high predictive accuracy.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/jco.2013.31.6_suppl.474
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2013
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
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