Markus Graefen

Universitätsklinikum Tübingen, Tübingen, Baden-Württemberg, Germany

Are you Markus Graefen?

Claim your profile

Publications (794)3912.14 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: In 2010, we published a review summarising the available literature on surgical anatomy of the prostate and adjacent structures involved in cancer control and the functional outcome of prostatectomy.
    No preview · Article · Feb 2016
  • [Show abstract] [Hide abstract]
    ABSTRACT: Purpose: Aberrant DNA content has been discussed as a potential prognostic feature in prostate cancer. Experimental design: We analyzed the clinical significance of DNA ploidy in combination with prognostic relevant deletions of PTEN and 6q15 in 3,845 prostate cancers. Result: The DNA status was diploid in 67.8%, tetraploid in 25.6% and aneuploid in 6.8% of tumors, and deletions of PTEN and 6q15 occurred in 17.8% and 20.3% of tumors. Abnormal DNA content and deletions were linked to high Gleason score, advanced tumor stage, and positive nodal stage (p<0.0001 each). The risk of PSA recurrence increased from diploid to tetraploid and from tetraploid to aneuploid DNA status (p<0.0001 each). However, 40% of patients with Gleason score ≥4+4 and 55% of patients with PSA recurrence had diploid cancers. This fraction decreased to 21% (Gleason ≥4+4) and 29% (PSA recurrence) if PTEN and/or 6q deletion data were added to ploidy data to identify cancers with an aberrant DNA status. The significance of combining both deletions and ploidy was further demonstrated in a combined recurrence analysis. Presence of deletions increased the risk of PSA recurrence in diploid (p<0.0001), tetraploid (p<0.0001), and aneuploid cancers (p=0.0049), and the combination of ploidy data and deletions provided clinically relevant information beyond the CAPRA-S nomogram. Multivariate modeling including preoperatively and postoperatively available parameters identified the "combined DNA status" as a strong independent predictor of poor patient outcome. Conclusion: The combinatorial DNA content analysis involving general (ploidy) and specific events (deletions) has the potential for clinical utility in prostate cancer.
    No preview · Article · Jan 2016 · Clinical Cancer Research
  • [Show abstract] [Hide abstract]
    ABSTRACT: Objective: To examine the characteristics of robot-assisted radical prostatectomy (RARP) and open radical prostatectomy (ORP) patients at a high-volume center. Patients and methods: We relied on the Martini-Clinic database and focused on prostate cancer patients treated in 2013. Characteristics in ORP and RARP patients were assessed. In multivariable logistic regression analyses (MVA), we predicted RARP treatment. Results: Of 1,920 patients, 575 (29.9%) underwent RARP and 1,345 (70.1%) ORP. RARP patients had a lower prostate-specific antigen (PSA), and were less likely to harbor pT3b, pathological Gleason ≥4 + 4 or lymph node metastases (all p < 0.05). Pelvic lymph node dissection (PLND) (84.3 vs. 87.0%, p = 0.1), as well as positive surgical margins (15.5 vs. 15.7%, p = 0.7) and the nerve-sparing status (p = 0.5) were comparable between RARP and ORP. Lymph node yield (median 11 vs. 16), and median blood loss (250 vs. 700 ml) were lower at RARP (all p < 0.001). Additionally, the median operating room time was higher at RARP (215 vs. 185 min, p < 0.001). In MVA, patients with body mass index (BMI) ≥30 were more likely to undergo RARP (OR 1.8, 95% CI 1.3-2.4, p < 0.001). Conversely, patients with PSA >20 ng/ml were less likely to undergo RARP (OR 0.6, 95% CI 0.4-1.0, p = 0.03). Conclusions: More favorable pathological characteristics were recorded at RARP. High BMI and low PSA were independent predictors for RARP. Treatment characteristics such as PLND rates, margin status and nerve sparing were comparable between RARP and ORP. Despite lower blood loss at RARP, a longer operating room time and lower yield of lymph nodes were recorded.
    No preview · Article · Jan 2016 · Urologia Internationalis
  • [Show abstract] [Hide abstract]
    ABSTRACT: Purpose: As life expectancy increases, oncological outcome in elderly patients ≥75 years is a salient topic requiring further investigation. Material and methods: A total of 13997 patients who underwent RP from 2006 to 2013 were analyzed. Known prognosticators were compared according to patient age at RP (13732 patients<75 years versus 265 patients≥75 years). Uni- and multivariate Cox regressions were used to estimate the impact of age on biochemical recurrence (BCR)-free survival, metastasis-free survival (MFS), cancer-specific survival (CSS) and overall survival (OS) RESULTS: Median follow up was 47.3 months. Patients ≥75 years compared to patients <75 years had a higher pathologic Gleason score (p<0.001), were more likely to harbor non-organ-confined tumor (p<0.001), to have positive surgical margin (p=0.004) and positive lymph nodes (p=0.028) and to receive salvage ADT (p=0.002). 5-year BCR-free survival, MFS, CSS and overall survival were 64.2%, 84.7%, 98.4% and 91.3% for patients ≥75 years and 76.9%, 96.2%, 99.0% and 96.2% for patients <75 years. In uni- and multivariate analysis age ≥75 was associated with a worse BCR-free survival and MFS. Patients ≥75 years were more likely to die from other causes than cancer. Nevertheless non-cancer related mortality was very low. Conclusions: Older patients who underwent RP had more advanced disease. Age itself is an independent predictor of worse BCR-free and MFS. Healthy and highly selected patients ≥75 years in our sample showed good long-term overall survival. Therefore, older age in well selected men should not be a contraindication for RP, especially in patients harboring high-risk disease.
    No preview · Article · Jan 2016 · The Journal of urology
  • [Show abstract] [Hide abstract]
    ABSTRACT: Purpose: Oncological surgery in immunosuppressed patients with solid organ transplantation (Tx) is challenging. These patients are thought to have higher postoperative morbidity and an increased rate of tumour progression. The aim of the present study was to analyse oncological, functional and perioperative outcomes in Tx patients following radical prostatectomy (RP). Materials and methods: Between 1996 and 2014, 30 patients diagnosed with prostate cancer underwent RP at our institution following Tx (kidney: n = 20, heart: n = 5, liver: n = 5). Functional, oncological and perioperative follow-ups were analysed. Postoperative complications were assessed using the Clavien-Dindo classification. Results: Median follow-up was 45 months. Median PSA was 5.3 ng/ml. Intraoperative blood loss was 600 ml at a median operating time of 180 min. Surgery in kidney Tx patients was technically feasible. Major complications occurred in 3 patients (ureteral injury, lymphocele and haematoma). Histological evaluation revealed n = 18 ≤pT2 tumours (60.0 %), n = 7 pT3a tumours (23.3 %) and n = 5 ≥pT3b tumours (16.7 %). Continence rate 12 months after surgery, defined as no or one safety pad use, was 73.3 %, while 93.3 % of the patients used ≤2 pads/24 h. After the median follow-up of 45 months, BCR-free survival was 69.0 %. In recurrent men, there was suspicion of metastasis in one patient. No cancer-specific death was observed. Five-year overall survival was 94.4 %. Conclusion: The complication rate in patients with solid organ transplantation after RP was low. While histopathological evaluation revealed disease characteristics comparable to non-transplant patients from current RP series, postoperative continence was worse. Immunosuppressive therapy does not seem to lead to an increased rate of tumour progression.
    No preview · Article · Jan 2016 · World Journal of Urology
  • [Show abstract] [Hide abstract]
    ABSTRACT: Objective: The aim of the study was to evaluate the impact of the clinical significance of incidental prostate cancer (PC) on overall survival (OS) after radical cystoprostatectomy (RC) for bladder cancer (BC). Methods: A total of 822 consecutive men underwent RC in 3 academic centers between 1996 and 2011. The clinical significance of incidental PC was determined according to the Epstein criteria. The Kaplan-Meier analysis with log-rank was used to investigate the impact of PC on OS and univariate and multivariate Cox regression analyses for risk factors of OS. The median follow-up was 36 months (interquartile range 10-49). Results: Of the 822 men, 117 (14.2%) had clinically significant, 243 (29.6%) insignificant and 462 (56.2) no PC at RC. Men with PC were at higher risk for lymphovascular invasion (LVI) of BC compared to men without PC (p < 0.001). The 5-year OS for men with clinically significant, insignificant and no PC was 33.3, 51.3 and 51.5%, respectively (p = 0.050). In the subgroup of pN0 patients (n = 601), clinically significant PC was significantly associated with inferior OS (p = 0.044) but not in multivariable analysis (p = 0.46). Conclusions: We did not find the clinical significance of incidental PC to be an independent predictor. However, the positive correlation between incidental PC and LVI of BC deserves further investigation.
    No preview · Article · Jan 2016 · Urologia Internationalis
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Objective: In patients with a long life expectancy with high-risk (HR) prostate cancer (PCa), the chance to die from PCa is not negligible and may change significantly according to the time elapsed from surgery. The aim of this study was to evaluate long-term survival patterns in young patients treated with radical prostatectomy (RP) for HRPCa. Materials and methods: Within a multiinstitutional cohort, 600 young patients (≤59 years) treated with RP between 1987 and 2012 for HRPCa (defined as at least one of the following adverse characteristics: prostate specific antigen>20, cT3 or higher, biopsy Gleason sum 8-10) were identified. Smoothed cumulative incidence plot was performed to assess cancer-specific mortality (CSM) and other cause mortality (OCM) rates at 10, 15, and 20 years after RP. The same analyses were performed to assess the 5-year probability of CSM and OCM in patients who survived 5, 10, and 15 years after RP. A multivariable competing risk regression model was fitted to identify predictors of CSM and OCM. Results: The 10-, 15- and 20-year CSM and OCM rates were 11.6% and 5.5% vs. 15.5% and 13.5% vs. 18.4% and 19.3%, respectively. The 5-year probability of CSM and OCM rates among patients who survived at 5, 10, and 15 years after RP, were 6.4% and 2.7% vs. 4.6% and 9.6% vs. 4.2% and 8.2%, respectively. Year of surgery, pathological stage and Gleason score, surgical margin status and lymph node invasion were the major determinants of CSM (all P≤0.03). Conversely, none of the covariates was significantly associated with OCM (all P≥ 0.09). Conclusions: Very long-term cancer control in young high-risk patients after RP is highly satisfactory. The probability of dying from PCa in young patients is the leading cause of death during the first 10 years of survivorship after RP. Thereafter, mortality not related to PCa became the main cause of death. Consequently, surgery should be consider among young patients with high-risk disease and strict PCa follow-up should enforce during the first 10 years of survivorship after RP.
    Full-text · Article · Dec 2015 · Urologic Oncology
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background: Gleason grading is the strongest prognostic parameter in prostate cancer. Gleason grading is categorized as Gleason ≤6, 3+4, 4+3, 8, and 9-10, but there is variability within these subgroups. For example, Gleason 4 components may range from 5-45% in a Gleason 3+4=7 cancer. Objective: To assess the clinical relevance of the fractions of Gleason patterns. Design, setting, and participants: Prostatectomy specimens from 12823 consecutive patients and of 2971 matched preoperative biopsies for which clinical data with an annual follow-up between 2005 and 2014 were available from the Martini-Klinik database. Outcome measurements and statistical analysis: To evaluate the utility of quantitative grading, the fraction of Gleason 3, 4, and 5 patterns seen in biopsies and prostatectomies were recorded. Gleason grade fractions were compared with prostatectomy findings and prostate-specific antigen recurrence. Results and limitations: Our data suggest a striking utility of quantitative Gleason grading. In prostatectomy specimens, there was a continuous increase of the risk of prostate-specific antigen recurrence with increasing percentage of Gleason 4 fractions with remarkably small differences in outcome at clinically important thresholds (0% vs 5%; 40% vs 60% Gleason 4), distinguishing traditionally established prognostic groups. Also, in biopsies, the quantitative Gleason scoring identified various intermediate risk groups with respect to Gleason findings in corresponding prostatectomies. Quantitative grading may also reduce the clinical impact of interobserver variability because borderline findings such as tumors with 5%, 40%, or 60% Gleason 4 fractions and very small Gleason 5 fractions (with pivotal impact on the Gleason score) are disclaimed. Conclusions: Quantitative Gleason pattern data should routinely be provided in addition to Gleason score categories, both in biopsies and in prostatectomy specimens. Patient summary: Gleason score is the most important prognostic parameter in prostate cancer, but prone to interobserver variation. The results of our study show that morphological aspects that define the Gleason grade in prostate cancer represent a continuum. Quantitation of Gleason patterns provides clinically relevant information beyond the traditional Gleason grading categories ≤3+3, 3+4, 4+3, 8, 9-10. Quantitative Gleason scoring can help to minimize variations between different pathologists and substantially aid in optimized therapy decision-making.
    No preview · Article · Nov 2015 · European Urology
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Summary There is substantial heterogeneity among primary prostate cancers, evident in the spectrum of molecular abnormalities and its variable clinical course. As part of The Cancer Genome Atlas (TCGA), we present a comprehensive molecular analysis of 333 primary prostate carcinomas. Our results revealed a molecular taxonomy in which 74% of these tumors fell into one of seven subtypes defined by specific gene fusions (ERG, ETV1/4, and FLI1) or mutations (SPOP, FOXA1, and IDH1). Epigenetic profiles showed substantial heterogeneity, including an IDH1 mutant subset with a methylator phenotype. Androgen receptor (AR) activity varied widely and in a subtype-specific manner, with SPOP and FOXA1 mutant tumors having the highest levels of AR-induced transcripts. 25% of the prostate cancers had a presumed actionable lesion in the PI3K or MAPK signaling pathways, and DNA repair genes were inactivated in 19%. Our analysis reveals molecular heterogeneity among primary prostate cancers, as well as potentially actionable molecular defects.
    Full-text · Article · Nov 2015 · Cell
  • B. Beyer · H. Huland · M. Graefen
    [Show abstract] [Hide abstract]
    ABSTRACT: Background Measurement of the quality of treatment has become increasingly important in hospitals. An easy and practical solution in data acquisition is the Patient-Reported Outcome Measurement (PROM). Methods In this article the historical development, general conditions, and difficulties of using the outcome measurement in our patients are describe. In addition, we illustrate the wide range of benefits due to our survey. Based on data from 2008–2013, the functional and oncological results of treatment in our clinic are shown. The main focus lies on the PROMs, e.g., urinary continence evaluated with the daily pad use, sexual function with the IIEF-5 questionnaire, and postoperative complications. Conclusions A systematic and standardized outcome measurement may help to improve the quality of treatment, provides factual information for patients, and supports medical development.
    No preview · Article · Nov 2015 · Der Urologe
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Purpose: To assess whether real-time elastography-targeted biopsy (RTE-bx) may help to correctly assign Gleason grade at radical prostatectomy (RP) and to compare discriminant properties of systematic biopsy alone (sbx) versus combination with RTE-bx (comb-bx) to distinguish between postoperatively favorable (Gleason 3 + 3, pT2, Nx/0) and postoperatively unfavorable (Gleason ≥4 + 4) prostate cancer (PCa) at RP. Patients and methods: Overall, 259 patients diagnosed with PCa at systematic biopsy in combination with RTE-bx underwent RP between 2008 and 2011. Gleason Score derived from sbx versus comb-bx was compared to the gold-standard RP, and discriminant properties were assessed. Specificity gains were examined for sbx versus comb-bx when the endpoint consisted of postoperatively favorable PCa at RP. Sensitivity gains were examined, when analyses focused on postoperatively unfavorable PCa. Results: Comb-bx resulted in higher correct overall Gleason assignment (68.3 vs. 56.7 %, p = 0.008) than sbx. Similarly, lower rates of undergrading (21.2 vs. 36.3 %, p < 0.001) were recorded. Specificity gains with comb-bx were 10 % (92 vs. 82 %, p = 0.004) for postoperatively favorable PCa. Comb-bx resulted in 31 % sensitivity gains relative to sbx (94 vs. 63 %, p = 0.03), when postoperatively unfavorable PCa was the endpoint. Conclusion: The agreement between biopsy and pathology Gleason Score was significantly higher for comb-bx than sbx. Additionally, comb-bx reduced the rate of false positives in the diagnosis of favorable PCa. Rates of correctly classified unfavorable PCa at RP were also higher for comb-bx. Those data indicate that comb-bx is useful in clinical practice.
    Full-text · Article · Oct 2015 · World Journal of Urology
  • Markus Graefen · Thorsten Schlomm · Guido Sauter · Hartwig Huland

    No preview · Article · Oct 2015 · European Urology
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background: ELAVL1 is an RNA binding protein involved in translation control, which might have a regulatory role in prostate cancer progress. Methods: To evaluate its impact and relationship with key genomic alterations, ELAVL1 expression was analyzed by immunohistochemistry on a tissue microarray containing 12,427 prostate cancers. Results: The analysis revealed a mild to moderate predominantly nuclear immunostaining in normal prostate epithelium and an often higher both cytoplasmic and nuclear expression in cancer cells. Weak, moderate, and strong cytoplasmic ELAVL1 staining was found in 43%, 18%, and 3% of 10,478 interpretable tumors. Strong ELAVL1 staining was linked to high Gleason grade, advanced pathological tumor stage, positive nodal status, and PSA recurrence (P<0.0001 each). A combined analysis of the effect of nuclear and cytoplasmic ELAVL1 expression on PSA recurrence revealed that the association with patient outcome was entirely driven by cytoplasmic staining. ELAVL1 positivity was more frequent in cancers harboring TMPRSS2:ERG fusions found by FISH (78%) or showing immunohistochemical ERG expression (74%) than in cancers without ERG rearrangement (63%) or ERG expression (58%, P<0.0001 each). Strong cytoplasmic ELAVL1 staining was further linked to presence of PTEN, 5q21, 6q15, and 3p13 deletions (P<0.0001 each), an observation consistent with cytoplasmic ELAVL1 accumulation in case of genomic instability. The prognostic role of ELAVL1 expression was independent of Gleason grade, T stage, N stage, surgical margin status, and preoperative PSA, irrespective of whether preoperative or postoperative variables were used for modeling. Conclusion: Our study identifies cytoplasmic accumulation of ELAVL1 as a predictor of adverse clinical behavior of prostate cancer independent of established clinico-pathological parameters.
    No preview · Article · Oct 2015 · The Prostate
  • [Show abstract] [Hide abstract]
    ABSTRACT: Introduction: High-dose-rate brachytherapy (HDR-BT) with external-beam radiation therapy and radical prostatectomy (RP) are common treatment options for clinically localized prostate cancer. The aim was to describe risk factors for biochemical recurrence (BCR) and death, as well as BCR rates and overall survival (OS) rates in both treatment groups. Patients and methods: Overall, 5,619 patients with localized prostate cancer underwent either RP (n = 5,200) or HDR-BT (n = 419) between 1999 and 2009. Median follow-up time was 72.4 months. Kaplan-Meier analyses and multivariable Cox regression analyses were performed for the overall cohort and for a propensity score-matched cohort to predict BCR and OS rates. Within the matched cohort, stratified analyses were repeated for HDR-BT alone (n = 206) and HDR-BT plus androgen deprivation therapy (ADT) (n = 213). Sensitivity analyses were performed to adjust for prostate-specific antigen rebound. Results: The 5-year BCR-free survival rates were 82.1% vs. 80.3% (P<0.01) for RP and HDR-BT, respectively. Corresponding 5-year OS rates were 97.1% vs. 92.4% (P<0.01). In the propensity score-matched cohort, 5-year BCR-free survival rates were 80.3% vs. 77.1%; P = 0.06 and 5-year OS rates were 95.7% vs. 92.4%; P = 0.5. In multivariable models, the overall HDR-BT exerted no significant effect on BCR, and the same results were recorded in the matched cohort. In stratified analyses, HDR-BT alone vs. RP increased BCR risk (1.45; P<0.01); conversely, HDR-BT plus ADT vs. RP decreased BCR risk (hazard ratio = 0.66; P = 0.02). Conclusions: First, RP offers equivalent oncological control without the need for concurrent hormone therapy and its morbidity. Second, patients who have RP avoid ADT (2%) and the need for salvage and adjuvant external-beam radiation therapy is low at 11% and 3%, respectively.
    No preview · Article · Oct 2015 · Urologic Oncology
  • [Show abstract] [Hide abstract]
    ABSTRACT: Aquaporin 5 (AQP5) is an androgen-regulated member of a family of small hydrophobic integral transmembrane water channel proteins regulating cellular water homeostasis and growth signaling. To evaluate its clinical impact and relationship with key genomic alterations in prostate cancer, AQP5 expression was analyzed by immunohistochemistry on a tissue microarray containing 12427 prostate cancers. The analysis revealed weak to moderate immunostaining in normal prostate epithelium. In prostate cancers AQP5 staining levels were more variable and also included completely negative and highly overexpressing cases. Negative, weak, moderate, and strong AQP5 staining was found in 25.0%, 32.5%, 32.5%, and 10.0% of 10239 interpretable tumors. Comparison of AQP5 expression levels with tumor characteristics showed a dichotomous pattern with both high and low staining levels being linked to unfavorable tumor phenotype. AQP5 was negative in 28%, 23%, 24%, and 35% of tumors with Gleason score ≤3 + 3, 3 + 4, 4 + 3 and ≥4 + 4, while the rate of strongly positive cases continuously increased from 7.0% over 10.0% and 12.0% to 13.0% in cancers with Gleason score ≤3 + 3, 3 + 4, 4 + 3 and ≥4 + 4. AQP5 expression was also related to ERG positivity and phosphatase and tensin homolog (PTEN) deletion (P < .0001 each). Strong AQP5 positivity was seen in 15.5% of ERG-positive and 5.8% of ERG-negative cancers (P < .0001) as well as in 14.7% of cancers with PTEN deletion and 9.4% of cancers without PTEN deletion. Remarkably, both negativity and strong positivity of AQP5 were linked to unfavorable disease outcome. This was however only seen in subgroups defined by TMPRSS2-ERG fusion and/or PTEN deletion. In summary, AQP5 can be both overexpressed and lost in subgroups of prostate cancers. Both alterations are linked to unfavorable outcome in molecularly defined cancer subgroups. It is hypothesized that this dichotomous role of AQP5 is due to two highly different mechanisms as to how the protein can influence cancer cells, that is, hydraulic motility regulation and Ras/MAPK pathway activation.
    No preview · Article · Oct 2015 · Human pathology
  • [Show abstract] [Hide abstract]
    ABSTRACT: Objective: The impact of positive surgical margin (SM) on cancer control outcomes in prostate cancer (PCa) patients is a subject of continuous debate. We test the hypothesis that the impact of SM on clinical recurrence (CR) rate may vary based on the other clinical/pathological characteristics of the tumor. Methods: We focused on 5,290 patients treated with robotic-assisted radical prostatectomy and pelvic node dissection, between 2002 and 2013, at three tertiary care centers. Regression tree analysis stratified patients into risk-groups based on their tumor characteristics and the corresponding CR rate. Kaplan-Meier log-rank and multivariable Cox regression models tested the relationship between SM status and CR rate in each tree-generated risk group. Results: Mean (median) follow-up time was 47.7 (39.0) months. Regression tree analysis that considered all available covariates, except SM status, divided patients based on their CR risk into the following risk groups: 1) high-risk (any pT3b/pT4 disease); 2) intermediate-risk (≤pT3a disease and pGS 8-10); 3) low risk (≤pT3a, pGS≤7, and PSA >9 ng/ml); 4) very low-risk (≤pT3a, pGS≤7, and PSA ≤9 ng/ml). Positive SM had a significant detrimental impact on CR risk only in 2 groups: intermediate-risk (p<0.001) and high-risk (p=0.01). These observations were confirmed at the multivariable analyses. Conclusions Our findings show that positive SM had a detrimental impact on CR only in a minority of patients (15%), specifically in those with very advanced pathological stage, and/or pathologically poorly differentiated tumor. For all the remaining patients (85%), positive SM by itself did not increase the risk of CR.
    No preview · Article · Sep 2015 · Journal of endourology / Endourological Society
  • [Show abstract] [Hide abstract]
    ABSTRACT: Enhancer of zeste homolog 2 (EZH2) plays an important role in tumor development and progression by interacting with histone and nonhistone proteins. In the current study, we analyzed prevalence and prognostic impact of EZH2 in prostate cancer. EZH2 expression was analyzed by immunohistochemistry on a tissue microarray containing more than 12400 prostate cancer specimens. Results were compared to tumor phenotype, biochemical recurrence and molecular subtypes defined by ERG status as well as genomic deletions of 3p, 5q, 6q and PTEN. EZH2 immunostaining was detectable in 56.6% of 10168 interpretable cancers and considered strong in 1.1%, moderate in 12.2% and weak in 43.3% of cases. High EZH2 expression was strongly associated with high Gleason grade (P < 0.0001), advanced pathological tumor stage (P < 0.0001), positive nodal status (P < 0.0001), elevated preoperative PSA level (P = 0.0066), early PSA recurrence (P < 0.0001) and increased cell proliferation P < 0.0001). High-level EZH2 staining was also associated with TMPRSS2:ERG rearrangement and ERG expression in prostate cancers (P < 0.0001) and was linked to deletions of PTEN, 6q15, 5q21 and 3p13 (P < 0.0001 each) particularly in ERG-negative cancers. The prognostic impact of EZH2 was independent of established pre- and postoperatively assessed clinicopathological parameters. EZH2 has strong prognostic impact in prostate cancer and might contribute to the development of a fraction of genetically instable and particularly aggressive prostate cancers. EZH2 analysis might therefore be of clinical value for risk stratification of prostate cancer.
    No preview · Article · Sep 2015 · Carcinogenesis
  • B Beyer · H Huland · G Feick · M Graefen
    [Show abstract] [Hide abstract]
    ABSTRACT: The standardized collation of the quality of treatment is a subject of discussion both nationally and internationally. This article presents the work of the International Consortium for Health Outcomes Measurement (ICHOM) and the validated German translation of the expanded prostate cancer index composite (EPIC-26). This questionnaire allows a standardized interdisciplinary collation of the quality of treatment for all therapy modalities of localized prostate cancer. Use of the ICHOM standard set and the EPIC-26 achieves a possibility for comparison of each form of therapy with respect to the curative success and the effect on health and quality of life of patients.
    No preview · Article · Sep 2015 · Der Urologe
  • Katharina Bohm · Markus Graefen

    No preview · Article · Sep 2015 · Aktuelle Urologie
  • [Show abstract] [Hide abstract]
    ABSTRACT: The evidence on the association between anthropometric measures quantifying body fatness and prostate cancer (PCa) risk is not entirely consistent. Associations among waist circumference (WC), waist-hip ratio, body mass index (BMI), and PCa risk were assessed in a population-based case-control study. The study included 1933 incident PCa cases diagnosed between 2005 and 2009. Population controls were 1994 age-matched (±5y) Montreal residents selected from electoral lists. Information on sociodemographics, medical history including PCa screening, height, weight, and waist and hip circumferences was collected through interviews. Logistic regression was used to assess odds ratios (ORs) for the association between anthropometric measures, and overall and grade-specific PCa. After adjustment for BMI, an excess risk of high-grade PCa (Gleason≥7) was associated with a WC ≥102cm (OR = 1.47 [1.22-1.78]) and with a waist-hip ratio >1.0 (OR = 1.20 [1.01-1.43]). Men with a BMI≥30kg/m(2) had a lower risk of PCa, regardless of grade. Restricting to subjects recently screened for PCa did not alter findings. Elevated BMI was associated with a lower risk of PCa, regardless of grade. Contrastingly, abdominal obesity, when adjusted for BMI, yielded results in the opposite direction. Taken together, our observations suggest that the specific body fat distribution (abdominal), for a given BMI, is a predictor of PCa risk, whereas BMI alone is not. BMI and abdominal obesity, especially when measured by the WC, should be examined conjointly in future studies on this issue and may require consideration at patient counseling. Copyright © 2015 Elsevier Inc. All rights reserved.
    No preview · Article · Aug 2015 · Urologic Oncology

Publication Stats

14k Citations
3,912.14 Total Impact Points


  • 2016
    • Universitätsklinikum Tübingen
      • Department of Urology
      Tübingen, Baden-Württemberg, Germany
  • 1997-2016
    • University Medical Center Hamburg - Eppendorf
      • Department of Urology
      Hamburg, Hamburg, Germany
  • 2015
    • Martini Ziekenhuis
      Groningen, Groningen, Netherlands
  • 2014
    • Duke University
      Durham, North Carolina, United States
  • 2006-2014
    • Prostate Cancer Research Institute
      Los Ángeles, California, United States
  • 2013
    • Ruhr-Universität Bochum
      Bochum, North Rhine-Westphalia, Germany
  • 1997-2013
    • University of Hamburg
      • Department of Urology
      Hamburg, Hamburg, Germany
  • 2012
    • Mater Misericordiae University Hospital
      • Department of Surgery
      Dublin, Leinster, Ireland
    • Cornell University
      Итак, New York, United States
  • 2011
    • Institut Paoli Calmettes
      Marsiglia, Provence-Alpes-Côte d'Azur, France
  • 2007-2011
    • Université de Montréal
      • Department of Surgery
      Montréal, Quebec, Canada
    • University of Milan
      Milano, Lombardy, Italy
  • 2010
    • Krankenhaus Düren gem. GmbH
      Düren, North Rhine-Westphalia, Germany
  • 2009-2010
    • Schön Klinik Hamburg
      Hamburg, Hamburg, Germany
    • Universitätsklinikum Freiburg
      Freiburg an der Elbe, Lower Saxony, Germany
    • University Hospital Essen
      • Klinik für Urologie
      Essen, North Rhine-Westphalia, Germany
  • 2007-2008
    • Università Vita-Salute San Raffaele
      Milano, Lombardy, Italy
  • 2002-2007
    • Memorial Sloan-Kettering Cancer Center
      • Epidemiology & Biostatistics Group
      New York, New York, United States
    • Erasmus Universiteit Rotterdam
      Rotterdam, South Holland, Netherlands
  • 2003
    • Karl-Franzens-Universität Graz
      Gratz, Styria, Austria
  • 2000
    • University of Miami
      • Department of Urology
      كورال غيبلز، فلوريدا, Florida, United States
    • Lund University
      • Department of Chemistry
      Lund, Skåne, Sweden