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Einleitung: Es gibt weiterhin keinen robusten prädiktiven Biomarker zur Vorhersage des Ansprechens gegenüber Immuncheckpoint-Blockade (ICB) beim metastasierten Urothelkarzinom (mUC.) Die frühe Kinetik des C-reaktiven Proteins (CRP) nach Einleitung der ICB und insbesondere das kürzlich [zum vollständigen Text gelangen Sie über die oben angegebene URL]

Einleitung: F��r die adjuvante Immuncheckpoint-Inhibition beim Nierenzellkarzinom (RCC) mit dem anti-PD-1-Inhibitor Pembrolizumab konnte erstmalig ein Vorteil im krankheitsfreien ��berleben nach Nephrektomie gezeigt werden (KEYNOTE-564). Es gilt nun, Subgruppen zu identifizieren die im Besonderen [zum vollst��ndigen Text gelangen Sie ��ber die oben angegebene URL]

Fragestellung: Die Durchf��hrung multiparametrischer Magnetresonanztomographien (mpMRT) vor Prostatabiopsien verbessert die Detektionsrate (CDR) von Prostatakarzinomen (PCA). Wir verglichen die Tumordetektionsrate der gezielten (TB) und systematischen (SB) mpMRT/Ultraschall-Fusionsbiopsien [zum vollst��ndigen Text gelangen Sie ��ber die oben angegebene URL]

BACKGROUND: Expression of circulating serum microRNAs has not been studied in a cohort of patients with papillary renal cell carcinoma (pRCC) so far. We hypothesized that miRNA deregulation in malignant tissue is reflected in serum and could be used for non-invasive diagnosis of pRCC as well as differentiation between type 1 and type 2 pRCC. METHODS: We selected 11 differentially regulated miRNAs from the Cancer Genome Atlas (TCGA) pRCC data set as potential serum validation candidates. Serum miRNA expression was determined by qRT-PCR in a total of 34 pRCC type 1, 33 pRCC type 2 and 33 control subjects of three german high-volume medical centers. RESULTS: Heatmap and principal component analysis showed that miRNA expression did not cluster the samples into distinct sample groups and that miRNA levels did not significantly discriminate healthy individuals from patients with pRCC, nor between patients with type 1 and type 2 pRCC. However, miR-21-5p levels were significantly increased in patients with advanced pRCC (>pT3, and/or pN+ and/or pM+) in comparison to localized pRCC. Moreover, adding the expression of miR-210-3p, which was significantly down-regulated in localized pRCC sera in comparison to healthy sera, additionally increased diagnostic accuracy in our study cohort. CONCLUSIONS: In our multicenter cohort, we were not able to identify a single miRNA serum marker for pRCC including its subclasses. However, our study revealed that miR-21-5p levels were elevated in advanced disease (with added diagnostic accuracy via addition of miR-210-3p expression), proposing these two miRs as potential biomarkers in pRCC.

Einleitung: Das Mikrotubuli-assoziierte Protein 2 (MAP2) ist ein Vertreter der Mikrotubuli-assoziierten Proteine (MAPs) der MAP2/Tau-Familie. MAP2 ist bekannt als ein dendritisches Strukturprotein, das im dendritischen Zytoplasma von Nervenzellen vorliegt. Es spielt eine entscheidende Rolle für[zum vollständigen Text gelangen Sie über die oben angegebene URL], 66. Kongress der Nordrhein-Westfälischen Gesellschaft für Urologie

AIMS: Nested variant of urothelial carcinoma (NVUC) is rare and only few small series exist. Molecular characteristics and the classifying marker profile as well as therapeutic targets of this specific variant are mostly unknown. Aim of this study was to characterize NVUC on the molecular level in one of the largest cohorts to date. In addition, we applied an immunohistochemical marker panel in order to define the molecular subtype. METHODS: 60 NVUC cases were collected from different departments. TERT mutation analysis was carried out in all samples using SNaPshot analysis. Target sequencing of 48 cancer related genes by Next Generation Sequencing (NGS) analysis was performed in a subset of 26 cases. Immunohistochemical markers CD44, CK5, CK14, EGFR, p63, FOXA1, GATA3, CD24 und CK20 were used to elucidate the molecular subtype. RESULTS: A total of 62.5% of NVUC cases harbored a mutation of the TERT promoter. Additionally, TP53, JAK3, and CTNNB1 were among the most frequently mutated genes identified by NGS analysis. Subtyping revealed that all NVUC express luminal markers such as CD24, FOXA1, GATA3 and CK20. CONCLUSIONS: Summarized, NVUC belong to the luminal molecular subtype. Moreover, a subset of NVUC seems to be characterized by mutations of the Wnt- and inflammatory pathway, including JAK3 mutations, indicating a different biological background compared to conventional urothelial bladder cancer.

In November, 2014, 65 prostate cancer pathology experts, along with 17 clinicians including urologists, radiation oncologists, and medical oncologists from 19 different countries gathered in a consensus conference to update the grading of prostate cancer, last revised in 2005. The major conclusions were: (1) Cribriform glands should be assigned a Gleason pattern 4, regardless of morphology; (2) Glomeruloid glands should be assigned a Gleason pattern 4, regardless of morphology; (3) Grading of mucinous carcinoma of the prostate should be based on its underlying growth pattern rather than grading them all as pattern 4; and (4) Intraductal carcinoma of the prostate without invasive carcinoma should not be assigned a Gleason grade and a comment as to its invariable association with aggressive prostate cancer should be made. Regarding morphologies of Gleason patterns, there was clear consensus on: (1) Gleason pattern 4 includes cribriform, fused, and poorly formed glands; (2) The term hypernephromatoid cancer should not be used; (3) For a diagnosis of Gleason pattern 4, it needs to be seen at 10x lens magnification; (4) Occasional/seemingly poorly formed or fused glands between well-formed glands is insufficient for a diagnosis of pattern 4; (5) In cases with borderline morphology between Gleason pattern 3 and pattern 4 and crush artifacts, the lower grade should be favored; (6) Branched glands are allowed in Gleason pattern 3; (7) Small solid cylinders represent Gleason pattern 5; (8) Solid medium to large nests with rosette-like spaces should be considered to represent Gleason pattern 5; and (9) Presence of unequivocal comedonecrosis, even if focal is indicative of Gleason pattern 5. It was recognized by both pathologists and clinicians that despite the above changes, there were deficiencies with the Gleason system. The Gleason grading system ranges from 2 to 10, yet 6 is the lowest score currently assigned. When patients are told that they have a Gleason score 6 out of 10, it implies that their prognosis is intermediate and contributes to their fear of having a more aggressive cancer. Also, in the literature and for therapeutic purposes, various scores have been incorrectly grouped together with the assumption that they have a similar prognosis. For example, many classification systems consider Gleason score 7 as a single score without distinguishing 3+4 versus 4+3, despite studies showing significantly worse prognosis for the latter. The basis for a new grading system was proposed in 2013 by one of the authors (J.I.E.) based on data from Johns Hopkins Hospital resulting in 5 prognostically distinct Grade Groups. This new system was validated in a multi-institutional study of over 20,000 radical prostatectomy specimens, over 16,000 needle biopsy specimens, and over 5,000 biopsies followed by radiation therapy. There was broad (90%) consensus for the adoption of this new prostate cancer Grading system in the 2014 consensus conference based on: (1) the new classification provided more accurate stratification of tumors than the current system; (2) the classification simplified the number of grading categories from Gleason scores 2 to 10, with even more permutations based on different pattern combinations, to Grade Groups 1 to 5; (3) the lowest grade is 1 not 6 as in Gleason, with the potential to reduce overtreatment of indolent cancer; and (4) the current modified Gleason grading, which forms the basis for the new grade groups, bears little resemblance to the original Gleason system. The new grades would, for the foreseeable future, be used in conjunction with the Gleason system [ie. Gleason score 3+3=6 (Grade Group 1)]. The new grading system and the terminology Grade Groups 1-5 have also been accepted by the World Health Organization for the 2016 edition of Pathology and Genetics: Tumours of the Urinary System and Male Genital Organs.

Einleitung: Das Mikrotubuli-assoziierte Protein 2 (MAP2) wird hauptsächlich in Nervenzellen exprimiert und fungiert als dendritisches Strukturprotein. Es spielt eine entscheidende Rolle für die Stabilisierung von Mikrotubuli, die Tubulinpolymerisation und die Verankerung von regulatorischen[zum vollständigen Text gelangen Sie über die oben angegebene URL], 65. Kongress der Nordrhein-Westfälischen Gesellschaft für Urologie