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Berlin Brandenburg

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  • 1
    Language: English
    In: European Urology, October 2018, Vol.74(4), pp.527-529
    Keywords: Medicine
    ISSN: 0302-2838
    E-ISSN: 1873-7560
    Source: ScienceDirect Journals (Elsevier)
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  • 2
    Language: English
    In: PLoS ONE, 01 January 2017, Vol.12(6), p.e0179602
    Description: PURPOSE:Genome-wide analyses revealed basal and luminal subtypes of urothelial carcinomas of the bladder. It is unknown if this subtyping can also be applied to upper tract urothelial carcinomas. MATERIALS AND METHODS:Tumor samples from 222 patients with upper tract urothelial carcinomas who were treated with radical nephroureterectomy were analyzed for the expression of seven basal/luminal immunohistochemical markers (CK5, EGFR, CD44, CK20, p63, GATA3, FOXA1). RESULTS:Hierarchical clustering revealed a basal-like subtype (enrichment of CK5, EGFR and CD44) in 23.9% and a luminal-like subtype (enrichment of CK20, GATA3, p63 and FOXA1) in 13.1% of the patients. In 60.8%, little to no markers were expressed, whereas markers of both subtypes were expressed in 2.2%. By using CK5 and CK20 as surrogate markers for the basal and luminal subtypes, we defined four subtypes of upper tract urothelial carcinomas: (i) exclusively CK20 positive and CK5 negative (CK20+/CK5-), (ii) exclusively CK5 positive and CK20 negative (CK20-/ CK5+), (iii) both markers positive (CK20+/CK5+) and (iv) both markers negative (CK20-/CK5-). A receiver-operator analysis provided the optimal cut-off values for this discrimination. An immunoreactive score 〉1 for CK5 and 〉6 for CK20 were defined as positive. In multivariate Cox's regression analysis, the CK20+/CK5- subtype was an independent negative prognostic marker with a 3.83-fold increased risk of cancer-specific death (p = 0.02) compared to the other three subtypes. CONCLUSIONS:Immunohistochemical subgrouping of upper tract urothelial carcinomas by analyzing CK5 and CK20 expression can be performed in a routine setting and can identify tumors with a significantly worse cancer-specific survival prognosis.
    Keywords: Sciences (General)
    E-ISSN: 1932-6203
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  • 3
  • 4
    Language: English
    In: Anticancer research, July 2015, Vol.35(7), pp.4277-81
    Description: To analyze female gender as a possible age-dependent prognostic factor for overall (OS) and cancer-specific survival (CSS) in patients with upper urinary tract urothelial carcinoma (UUTUC) after radical nephroureterectomy (RNU). A total of 167 men and 101 women with UUTUC treated with RNU with bladder cuff resection at our clinic were retrospectively analyzed. Female patients were divided into pre- and post-menopausal groups and compared against male patients of the same age. We used a cut-off age of 59 years or more as a surrogate for the post-menopausal hormonal status of women. Kaplan-Meier analyses and multivariate Cox proportional hazards regression analyses were performed to analyze gender as a possible prognostic factor of OS and CSS. Women aged 59 years or more had a significantly worse CSS with an average of 231 months after RNU compared to 303 months for their male counterparts (p=0.011). Univariate Cox regression analysis showed a 2.44-fold higher risk of death (p=0.013), while multivariate analyses, adjusted for tumor stage and tumor grade, showed a 2.92-fold higher risk (p=0.011) of cancer-specific death for women aged 59 years or more. Female gender is an age-dependent prognostic factor for CSS for patients with UUTUC treated with RNU.
    Keywords: Urothelial Carcinoma ; Age At Diagnosis ; Cancer-Specific Survival ; Gender ; Upper Urinary Tract ; Carcinoma -- Pathology ; Urinary Tract -- Pathology ; Urologic Neoplasms -- Pathology ; Urothelium -- Pathology
    ISSN: 02507005
    E-ISSN: 1791-7530
    Source: MEDLINE/PubMed (U.S. National Library of Medicine)
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  • 5
    Language: English
    In: Urologia internationalis, 2017, Vol.98(3), pp.262-267
    Description: With increasing life expectancy, curative treatment of octogenarians with urothelial carcinoma of the bladder (UCB) becomes more important. The treatment modalities of 276 octogenarians with UCB who were treated at the University Hospital of Erlangen between 1982 and 2011 were assessed retrospectively. One hundred forty-six patients had non-muscle invasive bladder cancer (NMIBC) while 71 had muscle invasive bladder cancer (MIBC). No data was available for 59 patients. Eighty-five (58.2%) of the 146 patients with NMIBC received transurethral resection of the bladder tumor (TURBT) only, another 38 patients (26%) underwent additional intravesical therapy; and 8.9% were treated with radiochemotherapy (RCT), 4.1% with radiotherapy (RT), 1.4% with systemic chemotherapy and 1.4% with radical cystectomy (RC). Of the 71 patients suffering from MIBC, 39 (54.9%) received TURBT alone. A potentially curative therapy was performed on 31 of the 71 patients with MIBC (43.7%). Of these, 16 patients (51.6%) received RCT, 9 patients (29.0%) RT and 6 patients (19.4%) RC. In Kaplan-Meier analysis, patients with MIBC had better median overall survival with curative treatment compared to TURBT alone (28 vs. 9 months; p 〈 0.001, log-rank test). By offering a wide range of treatment options, over 43% of octogenarians with MIBC received a curative therapy at a maximum care hospital.
    Keywords: Carcinoma -- Surgery ; Cystectomy -- Methods ; Urinary Bladder Neoplasms -- Surgery ; Urothelium -- Surgery
    ISSN: 00421138
    E-ISSN: 1423-0399
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  • 6
    Language: English
    In: BMJ Open, 13 November 2015, Vol.5(11)
    Description: To evaluate efficacy and safety of gonadotropin-releasing hormone (GnRH) antagonists compared to standard androgen suppression therapy for advanced prostate cancer.
    Keywords: Medicine;
    ISSN: 2044-6055
    ISSN: 20446055
    E-ISSN: 2044-6055
    E-ISSN: 20446055
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  • 7
    Language: English
    In: International Journal of Molecular Sciences, 01 October 2018, Vol.19(11), p.3396
    Description: Recently, muscle-invasive bladder cancer (MIBC) has been subclassified by gene expression profiling, with a substantial impact on therapy response and patient outcome. We tested whether these complex molecular subtypes of MIBC can be determined by mRNA detection of keratin 5 (KRT5) and keratin 20 (KRT20). Reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) was applied to quantify gene expression of KRT5 and KRT20 using TaqMan®-based assays in 122 curatively treated MIBC patients (median age 68.0 years). Furthermore, in silico analysis of the MD Anderson Cancer Center (MDACC) cohort (GSE48277 + GSE47993) was performed. High expression of KRT5 and low expression of KRT20 were associated with significantly improved recurrence-free survival (RFS) and disease-specific survival disease specific survival (DSS: 5-year DSS for KRT5 high: 58%; 5-year DSS for KRT20 high: 29%). KRT5 and KRT20 were associated with rates of lymphovascular invasion and lymphonodal metastasis. The combination of KRT5 and KRT20 allowed identification of patients with a very poor prognosis (KRT20+/KRT5−, 5-year DSS 0%, p 〈 0.0001). In silico analysis of the independent MDACC cohorts revealed congruent results (5-year DSS for KRT20 low vs. high: 84% vs. 40%, p = 0.042). High KRT20-expressing tumors as well as KRT20+/KRT− tumors were significantly enriched with aggressive urothelial carcinoma variants (micropapillary, plasmacytoid, nested).
    Keywords: Bladder Cancer ; Muscle-Invasive Bladder Cancer ; Molecular Diagnostics ; Molecular Subtyping ; Krt5 ; Krt20 ; Biology
    ISSN: 16616596
    E-ISSN: 1422-0067
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  • 8
    Language: English
    In: Clinical Genitourinary Cancer, August 2018, Vol.16(4), pp.248-256.e2
    Description: Identifying pT1 bladder cancer with high risk for progression remains a challenge. Aberrations in cyclin-dependent kinase inhibitor 2A (CDKN2A)/p16 and fibroblast growth factor receptor 3 (FGFR3) expression are the most common in urothelial bladder cancer. In the study at hand, we could show that high CDKN2A/p16 mRNA expression is associated with the luminal subtype and high CDKN2A/p16 as well as low FGFR3 mRNA expression are associated with worse progression-free survival. A recent study on the comprehensive genomic profile of advanced urothelial bladder cancer (UBC) showed cyclin-dependent kinase inhibitor 2A (CDKN2A) and fibroblast growth factor receptor 3 (FGFR3) as the most often clinically relevant genomic alterations. Therefore, the prognostic role of FGFR3 and CDKN2A/p16 for pT1 UBC was studied. Clinical data and formalin-fixed paraffin-embedded tissues of pT1 UBC treated with an organ-preserving approach was analyzed retrospectively. Total RNA was isolated using commercial RNA extraction kits and mRNA expression of CDKN2A/p16 and FGFR3 was measured using single step reverse transcription quantitative real time polymerase chain reaction using RNA-specific TaqMan assays. Data from 296 patients (79.4% male; median age: 72 years) could be used for the final evaluation. Spearman correlation revealed a statistically significant negative correlation between mRNA expression of CDKN2A/p16 and FGFR3. There was a positive correlation between CDKN2A/p16 and G3 tumors (ρ = 0.1875;  = .0012) and associated carcinoma in situ (ρ = 0.1703,  = .0033) and a negative correlation between FGFR3 and these factors (ρ = −0.2791,  〈 .0001 and ρ = −0.2182,  = .0002). High CDKN2A/p16 expression (≥38.04) and low FGFR3 expression (〈39.14) were statistically significantly associated with worse progression-free survival (PFS;  = .0194 and  = .0089). Multivariate Cox regression analysis could identify patients with low FGFR3 and high CDKN2A/p16 expression (log rank (LR) χ  = 10.69;  = .0048) as well as tumor size ≥3 cm (LR χ  = 6.03;  = .0141) as independent predictors for PFS. High expression of CDKN2A/p16 and low expression of FGFR3 show a correlation with established prognostic features for non–muscle-invasive bladder cancer and can predict progression of stage pT1 UBC.
    Keywords: Cdkn2a ; Mrna ; Nmibc ; P16 ; Prognosis ; Medicine
    ISSN: 1558-7673
    E-ISSN: 1938-0682
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  • 9
    Language: English
    In: Scientific reports, 06 December 2018, Vol.8(1), pp.17693
    Description: Piwi-like proteins are essential for stem-cell maintenance and self-renewal in multicellular organisms. We analyzed the expression of Piwi-like 1 and Piwi-like 2 by immunohistochemistry (IHC) in 95 muscle invasive bladder cancer (MIBC) samples using tissue microarray. Application of an immunoreactive score (IRS) revealed 37 and 45 patients who were Piwi-like 1 and -2 positive (IRS 〉 2). IHC results were correlated with clinico-pathological and survival data. The expression of both proteins was positively correlated with each other, lymph node metastasis and expression of CK20 and GATA 3. A negative correlation for both proteins was detected for disease-specific survival (DSS), recurrence, Ki67/MIB1 proliferation index, and CK5 expression. Detection of Piwi-like 1 protein positivity was associated with poor DSS (P = 0.019; log rank test, Kaplan-Meier analysis), and in multivariate Cox's analysis (adjusted to tumor stage and tumor grade), it was an independent prognostic factor for DSS (RR = 2.16; P = 0.011). Piwi-like 2 positivity was associated with DSS (P = 0.008) and recurrence-free survival (RFS; P = 0.040), and in multivariate Cox's analysis, Piwi-like 2 positivity was an independent prognostic factor for DSS (RR = 2.46; P = 0.004) and RFS (RR = 3.0; P = 0.003). Most interestingly, in the basal type patient subgroup (CK5+/GATA3-), Piwi-like 2 positivity was associated with poorer DSS, OS and RFS (P 〈 0.001, P = 0.004 and P = 0.05; log rank test). In multivariate analysis, Piwi-like 2 positivity was an independent prognostic factor for DSS (RR = 12.70; P = 0.001), OS (RR = 6.62;  = 0.008) and RFS (RR=13.0; P = 0.040). In summary, Piwi-like 1 and -2 positivity are associated with clinico-pathological factors and survival. Both Piwi-like proteins are suggested as biomarkers for MIBC patients.
    Keywords: Argonaute Proteins -- Metabolism ; Muscles -- Metabolism ; Urinary Bladder Neoplasms -- Metabolism
    ISSN: Scientific Reports
    E-ISSN: 2045-2322
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  • 10
    Language: English
    In: Translational Oncology, June 2017, Vol.10(3), pp.340-345
    Description: High-risk non–muscle-invasive bladder cancer (NMIBC) remains challenging given the high probability of progression. Given that the androgen receptor (AR) has been discussed as a possible factor in the development and progression of bladder cancer, we investigated the predictive value of AR in stage pT1 NMIBC. We retrospectively analyzed the clinical data and AR mRNA expression in 296 patients with stage pT1 NMIBC who underwent a transurethral resection of the bladder. The mRNA expression of the AR transcript variants 1 (AR1) and 2 (AR2) was measured by reverse transcription quantitative real-time polymerase chain reaction. AR expression was also correlated to KRT5 and KRT20 mRNA expression. Kaplan-Meier analysis indicated that high AR1 mRNA expression ≥35.47 is associated with statistically significant better recurrence-free survival (RFS) ( = .0007), progression-free survival (PFS) ( = .0420), and cancer-specific survival (CSS) ( = .0050). Multivariate Cox regression analysis revealed that high AR1 mRNA expression is an independent prognostic marker for RFS ( = .0029) and CSS ( = .0119). Spearman rank correlation revealed a significant positive association between mRNA expression of AR1 and KRT5 ( : 0.3171, 〈 .0001) as well as a negative association with multifocal tumors ( : 0.1478, 〈 .0109). No association was noted between AR1 expression and tumor grade, concomitant CIS, gender, tumor size, and KRT20 in patients with stage T1 NMIBC. AR mRNA expression can predict RFS and CSS in patients with stage T1 NMIBC. Further studies are necessary to refine the relevance of AR mRNA expression compared with immunohistochemically detectable AR expression.
    Keywords: Medicine
    ISSN: 1936-5233
    E-ISSN: 1936-5233
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