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Prognostische und prädiktive molekulare Marker urologischer Tumoren

Prognostic and predictive molecular markers for urologic cancers

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Zusammenfassung

Molekulare Prognosefaktoren und genetische Veränderungen als prädiktive Marker für die Wirksamkeit spezifischer Target-Therapien sind bei vielen malignen Tumoren in den klinischen Alltag eingezogen. Bei urologischen Tumoren wurden zwar in den letzten Jahren zahlreiche molekulare Marker identifiziert. Diese werden heute jedoch noch nicht in der Klinik genutzt. Beim Prostatakarzinom haben moderne Sequenzierverfahren ein immer differenzierteres Bild der molekularen Grundlagen geliefert. Es zeichnet sich ab, dass durch die Kombination klassischer histologischer und validierter molekularer Marker Verbesserungen in der Prognoseabschätzung zu erwarten sind, die zukünftig für mehr Patienten eine „Active Surveillance“ als realistische Therapieoption erscheinen lassen. Beim Urothelkarzinom sind neben klassischen histopathologischen Faktoren v. a. die Proliferation des Tumors, der Mutationsstatus für proliferationsfördernde Onkogene und Veränderungen in Genen, die zur Invasion und Metastasierung führen, von wesentlicher Bedeutung. Zusätzlich konnten Genexpressionsprofile identifiziert werden, die aggressive, metastasierende von nicht-metastasierenden Tumoren unterscheidet und somit in Zukunft Patienten selektieren könnten, die eine systemische perioperative Therapie benötigen. Für die Nierenzellkarzinome wurden eine ganze Reihe molekularer Marker identifiziert, die eine Korrelation mit der Prognose im Sinne der Metastasierung und dem Überleben der Patienten zeigen. Ein Teil dieser Marker konnte auch als unabhängige Prognoseparameter bestätigt werden. In Zukunft scheint damit eine Selektion von Patienten, die ein erhöhtes Metastasierungsrisiko bei primär organbegrenzten Tumoren haben und einer adjuvanten systemischen Therapie zugeführt werden sollten, möglich.

Abstract

Molecular prognostic factors and genetic alterations as predictive markers for cancer-specific targeted therapies are used today in the clinic for many malignancies. In recent years, many molecular markers for urogenital cancers have also been identified. However, these markers are not clinically used yet. In prostate cancer, novel next-generation sequencing methods revealed a detailed picture of the molecular changes. There is growing evidence that a combination of classical histopathological and validated molecular markers could lead to a more precise estimation of prognosis, thus, resulting in an increasing number of patients with active surveillance as a possible treatment option. In patients with urothelial carcinoma, histopathological factors but also the proliferation of the tumor, mutations in oncogenes leading to an increasing proliferation rate and changes in genes responsible for invasion and metastasis are important. In addition, gene expression profiles which could distinguish aggressive tumors with high risk of metastasis from nonmetastasizing tumors have been recently identified. In the future, this could potentially allow better selection of patients needing systemic perioperative treatment. In renal cell carcinoma, many molecular markers that are associated with metastasis and survival have been identified. Some of these markers were also validated as independent prognostic markers. Selection of patients with primarily organ-confined tumors and increased risk of metastasis for adjuvant systemic therapy could be clinically relevant in the future.

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Einhaltung ethischer Richtlinien

Interessenkonflikt. Arndt Hartmann, Torsten Schlomm, Simone Bertz, Joana Heinzelmann, Sebastian Hölters, Ronald Simon, Robert Stoehr und Kerstin Junker geben an, dass kein Interessenkonflikt besteht. Dieser Beitrag beinhaltet keine Studien an Menschen oder Tieren.

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Authors and Affiliations

  1. Institut für Pathologie, Universität Erlangen, Erlangen, Deutschland

    A. Hartmann, S. Bertz & R. Stoehr

  2. Martini-Klinik, Prostatakarzinomzentrum und Institut für Pathologie, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Deutschland

    T. Schlomm & R. Simon

  3. Klinik für Urologie und Kinderurologie, Universitätsklinikum des Saarlandes, Kirrbergerstraße 1, 66424, Homburg, Deutschland

    J. Heinzelmann, S. Hölters &  K. Junker

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  1. A. Hartmann
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  2. T. Schlomm
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  4. J. Heinzelmann
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Correspondence to K. Junker.

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A. Hartmann, T. Schlomm und K. Junker, sind zu gleichen Teilen an dieser Arbeit beteiligt. S. Bertz und R. Stoehr sind als Koautoren an dem Abschnitt zum Harnblasenkarzinom beteiligt. R. Simon ist als Koautor an dem Abschnitt zum Prostatakarzinom beteiligt. J. Heinzelmann und S. Hölters sind als Koautoren an dem Abschnitt Nierenzellkarzinom beteiligt.

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Hartmann, A., Schlomm, T., Bertz, S. et al. Prognostische und prädiktive molekulare Marker urologischer Tumoren. Urologe 53, 491–500 (2014). https://doi.org/10.1007/s00120-014-3442-3

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