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  • 1
    Language: English
    In: The Journal of Urology, April 2012, Vol.187(4), pp.e535-e535
    Keywords: Medicine
    ISSN: 0022-5347
    E-ISSN: 1527-3792
    Source: ScienceDirect Journals (Elsevier)
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  • 2
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  • 4
    In: BJU International, February 2012, Vol.109(4), pp.634-638
    Description: To authenticate to the full-text of this article, please visit this link: http://dx.doi.org/10.1111/j.1464-410X.2011.10392.x Keywords: renal cell carcinoma (RCC); XPA-210; proliferation; oncocytoma; biomarker; thymidine kinase 1 Abstract: What's known on the subject? and What does the study add? The exposed proliferation antigen 210 (XPA-210) of the proliferation marker thymidine kinase 1 (TK1) showed higher expression levels in metastatic renal cell carcinoma. The current study used a new XPA-210 antibody to clarify the role of TK1 tissue expression in the largest reported cohort of different renal cell carcinoma types and oncocytomas. OBJECTIVE To determine the clinical role of the exposed proliferation antigen 210 (XPA-210) of the proliferation marker thymidine kinase 1 (TK1) in a large cohort of different renal cell carcinoma (RCC) types, oncocytomas and normal renal tissues samples, as TK1 is reported to be of clinical significance in several cancer entities and is suggested as a prognostic serum biomarker for RCC. PATIENTS AND METHODS Expressions of XPA-210 were determined immunohistochemically in 40 clear cell RCCs (ccRCC), 25 papillary RCCs (papRCC), 17 chromophobe RCC (chRCC), 27 oncocytomas and 64 normal renal parenchyma paraffin-embedded specimens. Immunohistochemistry was performed with a monoclonal anti-XPA-210 antibody. Staining was measured by the percentage of positive cells. Expression was compared between subgroups and correlated with respective clinical data using one-way analysis of variance with post hoc Tukey-Kramer analyses. RESULTS XPA-210 staining in the RCC subgroup was significantly different from the oncocytomas (mean [ sem] 4.1 [0.4] vs 2.2 [0.4]; P = 0.004) and from normal renal tissue (1.0 [0.1]; P 〈 0.001], whereas oncocytomas did not differ from normal renal parenchyma staining (P = 0.18). Subdivided into RCC groups, only ccRCC (mean [ sem] 5.1 [0.6]; P 〈 0.001) and papRCC (4.4 [0.6]; P 〈 0.001) varied from normal renal parenchyma, whereas chRCC (1.4 [0.3]; P = 0.99) did not. RCC XPA-210 staining was significantly associated with higher tumour stage (T = 3, P = 0.002) and grade (G = 3, P = 0.001). CONCLUSIONS The malignant character of RCC is reflected by higher XPA-210 expression as compared with oncocytomas and normal kidney. The ccRCC and papRCC subgroups had higher XPA-210 levels. XPA-210 could be considered a potential marker for the assessment of the proliferative activity in primary RCC. Author Affiliation: (1)Departments of Urology (*)Pathology, Eberhard-Karls University, Tuebingen, Germany ([dagger])Alere North America, Inc., San Diego, CA, USA Article History: Accepted for publication 16 March 2011 Article note: Christian Schwentner, Department of Urology, Eberhard-Karls University Tuebingen, Hoppe-Seyler Strasse 3, 72076 Tuebingen, Germany. e-mail: Christian.schwentner@med.uni-tuebingen.de
    Keywords: Renal Cell Carcinoma Rcc ; Xpa‐210 ; Proliferation ; Oncocytoma ; Biomarker ; Thymidine Kinase 1
    ISSN: 1464-4096
    E-ISSN: 1464-410X
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  • 5
    Language: English
    In: World Journal of Urology, 2013, Vol.31(2), pp.351-358
    Description: BACKGROUNDGalactin-3 is a cell adhesion molecule involved in tumor progression. Our aim was to examine Gal-3 expression in tumor, benign tissue adjacent to the tumor (adjacent-benign) and benign prostate specimens and correlated it with biochemical recurrence. MATERIALS AND METHODSTissue microarrays were prepared from 83 tumor, 78 adjacent-benign and 75 benign tissues obtained from 83 patients undergoing prostatectomy for clinically localized prostate cancer. Tissues were stained using a Gal-3 antibody and immunohistochemistry. The staining was graded between 0 and 300 depending upon staining intensity and the area of staining. In 37 patients on whom there was follow-up (Mean: 57.8 months; Median: 68 months), staining intensity was correlated with biochemical recurrence. RESULTSGal-3 showed both nuclear and cytoplasmic localization in benign, adjacent-benign and tumor tissues. Median Gal-3 staining scores significantly decreased from benign (192.5) to adjacent-benign (148.8 p = 0.007) and to tumor (108.8; p 〈 0.0001) tissues. In univariate analysis, age (p = 0.028), Gleason sum (p = 0.007), T stage (p = 0.011), seminal vesicle invasion (p = 0.009), pre-operative prostate-specific antigen (p = 0.045) and Gal-3 staining in tumor tissues (0.018) significantly correlated with biochemical recurrence. In multivariate analysis, Gal-3 expression in tumor (p = 0.04), adjacent-benign (p = 0.037) and benign (p = 0.005) tissues significantly correlated with biochemical recurrence. Gal-3 staining in tumor tissues had 91.7 % sensitivity, 64 % specificity and 73 % accuracy in predicting biochemical recurrence. CONCLUSIONSThis is the first study that showed a decreasing gradient of Gal-3 expression in benign, adjacent-benign and tumor tissues. Gal-3 expression may be useful in predicting biochemical recurrence.
    Keywords: Galectin-3 ; Biochemical recurrence ; Prostate cancer ; Tissue microarray
    ISSN: 0724-4983
    E-ISSN: 1433-8726
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  • 6
    Language: English
    In: Urologia Internationalis, May 2010, Vol.84(4), pp.388-394
    Description: Objectives: Endorectal coil magnetic resonance imaging (EC-MRI) is useful to evaluate prostate cancer localization. Herein, we evaluate sensitivity and specificity of EC-MRI in different regions of the prostate by comparing the acquired images to whole-mount sections of the prostate after radical prostatectomy. Methods: 69 patients with localized prostate cancer were included. After virtually dividing the prostate into 12 sectors, results of EC-MRI were compared to corresponding whole-mount sections by contingency analysis. Sensitivity and specificity were calculated for each of the 12 areas as well as for the dorsal and ventral region. Results: Sensitivity right/left was dorsal apex/mid/base 41/41, 60/67 and 73/79%; ventral 33/52, 43/42 and 47/52%. Specificity right/left was dorsal apex/mid/base 92/89, 82/75 and 88/69%; ventral 100/100, 100/92 and 88/83%. Local sensitivity and specificity regarding dorsal versus ventral was 88/100 and 65/87%. Conclusions: Local sensitivity decreased from basodorsal to apicoventral direction, whereas local specificity increased in the same direction. Therefore, prostate cancers demonstrated by MRI are more prone to be detected in the basodorsal region, whereas less false-positive results are found in the apicoventral region. These variations in topographical specificity and sensitivity need to be considered before radical prostatectomy or MRI-guided biopsy.
    Keywords: Original Paper ; Endorectal Coil ; Local Staging ; Magnetic Resonance Imaging ; Radical Prostatectomy ; Endorectal Coil Magnetic Resonance Imaging, Sensitivity and Specificity ; Medicine
    ISSN: 0042-1138
    E-ISSN: 1423-0399
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  • 7
    Language: English
    In: World Journal of Urology, 2012, Vol.30(4), pp.547-552
    Description: XPA-210 is a proliferation marker derived from Thymidine kinase-1. It is of clinical significance in kidney, breast, and bladder cancer. There are no data available for XPA-210 in prostate cancer (PC). Herein, we aim to determine the clinical usefulness of XPA-210 in PC.In a retrospective study, cancer and benign tissue samples of 103 patients (median age 65 years, median PSA 9.04 ng/ml, median Gleason score 6) who underwent prostatectomy were constructed to a tissue micro array and stained for XPA-210. Semi-quantitative results were correlated with pathological and clinical data by Wilcoxon–Kruskall–Wallis and linear regression analysis. Expression levels in PC were correlated between the time of biochemical recurrence and the time to development of metastasis by the Kaplan–Meier method. Multivariate analysis was done to correlate those with the resection status.Mean staining score was 0.51–0.14 for tumor and benign tissue (P 〈 0.0001). Tumor staining score was significantly associated with Gleason score 〈6/≥6 (P 〈 0.0001) and T2/T 〉2 (P = 0.0007). When dividing the tumor score by the mean value, higher expression of XPA-210 was associated with a shorter time to biochemical recurrence (P = 0.003) and time to development of metastasis (P = 0.0061). Tumor staining (P = 0.0371) was an independent prognostic factor for biochemical relapse regardless of resection status.XPA-210 is a new tissue-based prognostic marker for prostate cancer histopathology. It reliably differentiates tumor and normal prostatic tissue predicting biochemical relapse and onset of metastatic disease. XPA-210 might be clinically useful for individual decision-making in PC-treatment.
    Keywords: Prostate cancer ; XPA-210 ; Biochemical recurrence ; Metastatic disease ; Proliferation
    ISSN: 0724-4983
    E-ISSN: 1433-8726
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  • 8
    Language: English
    In: World Journal of Urology, 2013, Vol.31(2), pp.345-350
    Description: BACKGROUND: Preclinical studies demonstrated effects of drugs inhibiting the mevalonate pathway including nitrogen-containing bisphosphonates (N-BPs) and statins on tumor growth and progression. The exact role of this pathway in prostate cancer (PC) has not been identified yet. Herein, we evaluate the expression of farnesyl pyrophosphate synthase (FPPS), the key enzyme of the mevalonate pathway, in PC.PATIENTS AND METHODS: Prostate cancer (PC) and benign prostate tissue of 114 men who underwent radical prostatectomy were constructed to a tissue microarray. Immunohistochemical staining of FPPS was quantified by the Remmele/Stegner immunoreactivity-score. Patients' clinical follow-up was assessed. IRS was correlated to pathological and clinical data. The impact of FPPS expression on clinical course was assessed univariate and multivariate.RESULTS: Mean IRS in PC and benign tissue was 5.7 (95% CI 5.0-6.5) and 2.6 (2.1-3.0, p〈0.0001). Mean IRS in PC tissue of patients with organ-confined and locally advanced disease (pT≥3) was 5.09 (4.22-5.96) and 6.87 (5.57-8.17, p=0.035). IRS of PC tissue significantly correlated with Gleason score (p=0.03). Patients with PC tissue IRS 〉3 showed shorter recurrence-free survival compared to the remaining (p=0.01). Increased FPPS expression is an independent risk factor for early biochemical recurrence (p=0.032).CONCLUSIONS: This is the first study on FPPS in PC specimens. The association of FPPS with established histopathological risk parameters and biochemical recurrence implicates a contribution of the mevalonate pathway to PC progression. Further functional analysis is required to explore the role of this pathway in PC and to investigate whether FPPS expression affects the response of PC cells to N-BPs.
    Keywords: Prostate cancer ; Bisphosphonates ; Farnesyl pyrophosphate synthase ; Zoledronic acid ; Mevalonate pathway
    ISSN: 0724-4983
    E-ISSN: 1433-8726
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  • 9
    Language: English
    In: Urologia Internationalis, June 2011, Vol.86(4), pp.393-398
    Description: Objectives: Endorectal coil MRI (endoMRI) of the prostate is useful to evaluate tumor localization. There is little evidence on patient characteristics affecting its diagnostic performance. We evaluate the influence of clinical and histological parameters on the accuracy of endoMRI. Methods: Sixty-nine patients with prostate cancer were included. After virtually dividing the prostate into pixels of 1 cm2, results of endoMRI were compared with those from prostatectomy specimens’ whole-mount sections. Univariate and multivariate analyses were performed to calculate the impact of clinical and histological parameters on the number of appropriately described pixels. Results: In 9, no tumor could be demonstrated by endoMRI. 48.3% of patients were staged correctly, 23.3% were over- and 28.3% understaged. Mean rates of correctly labeled pixels were 0.44 (± 0.04 SEM) for tumor and 0.90 (± 0.01) for benign segments. In univariate analysis, the rate of correctly labeled tumor segments showed significant positive correlations with Gleason score ≧7 and negative correlations with prostate weight and multifocality. The rate of correctly labeled benign segments showed significant negative correlation with tumor weight. All factors were independent variables in multivariate analysis. Conclusions: The reliability of endoMRI depends on clinical parameters. Higher Gleason scores, unifocal tumors and smaller prostate volumes ameliorate endoMRI performance.
    Keywords: Original Paper ; Endorectal Coil ; Local Staging ; Radical Prostatectomy ; Prostate Cancer ; Magnetic Resonance Imaging ; Medicine
    ISSN: 0042-1138
    E-ISSN: 1423-0399
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