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Identifizierung von diagnostischen Tumormarkern und therapeutischen Zielstrukturen in Hodentumoren

Identification of diagnostic tumour markers and therapeutic targets in testicular tumours

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Zusammenfassung

Die morphologische Vielfalt maligner Tumoren kann schon innerhalb einer organtypischen Tumorentität beobachtet werden. Diese rein morphologisch definierte Diversifikation maligner Tumoren hatte schon immer individuell abgestimmte Therapiestrategien zur Folge. Heute erfährt die Tumorklassifizierung infolge immunhistochemischer und molekularpathologischer Analysen eine erneute Erweiterung aufgrund entsprechender Muster/Profile der Protein- und Genexpression. Letztere Analysen betreffen häufig Wachstumsfaktoren und deren Liganden, intrazelluläre Signalwege, DNS(Desoxyribonukleinsäure)-bindende Proteine sowie Onkogene und Suppressorgene und umfassen somit funktionell v. a. die Regulation des Wachstums einschließlich Angiogenese und Regulation der Apoptose sowie die Induktion von Metastasen aufgrund von Störungen der Adhäsion und der Migration. Ausgehend von Beobachtungen, dass Tumoren des Hodens häufig Mikroverkalkungen zeigen, die möglicherweise durch einen gestörten Kalziumstoffwechsel bedingt sind, konzentrierten wir uns bei der Suche nach neuen Tumormarkern und therapeutischen Zielstrukturen auf calciumabhängige Transmembranproteine, speziell die Cadherine. N‑Cadherin wird in den verschiedenen Subtypen der Keimzelltumoren unterschiedlich exprimiert und eignet sich in N‑Cadherin-positiven Keimzelltumoren aufgrund funktioneller Analysen als eine neue therapeutische Zielstruktur, insbesondere bei Cisplatin-Resistenz. In den Keimstrang-Gonadenstroma-Tumoren ermöglichen Cadherine nachgeschalteter Proteine wie z. B. β‑Catenin und der Transkriptionsfaktor SOX9 („sex determining region 9“) eine eindeutige Klassifizierung dieser Tumoren. Morphologische Untersuchungen erweisen sich somit als Lotsen, um das Spektrum funktionell bedeutender Proteine zielgerichtet einzuengen, und somit Erfolg versprechend neue differentialdiagnostische Marker oder Zielstrukturen zu etablieren.

Abstract

Today, tumour classification has been expanded due to immunohistochemical and molecular–pathological analyses due to corresponding patterns/profiles of protein and gene expression. The latter analyses often include growth factors and their ligands, intracellular signalling pathways, DNA-binding proteins, and oncogenes and suppressor genes, thus functionally including primarily the regulation of growth including angiogenesis and apoptosis as well as the induction of metastases to adhesion and migration disorders. Based on observations that testicular tumours often show microcalcifications, possibly due to impaired calcium metabolism, we focused on calcium-dependent transmembrane proteins, particularly cadherins, in the search for new tumour markers and therapeutic targets. N‑cadherin is expressed differently in the various subtypes of germ cell tumours and is useful in N‑cadherin-positive germ cell tumours as a novel therapeutic targeting structure, particularly in cisplatin resistance, due to functional analysis. In the tumours of the sex cord stroma beta-catenin and the transcription factor SOX-9 give a clear classification of these tumours. Thus, morphological investigations prove to be pilot experiments to purposefully narrow the spectrum of functionally important proteins and thus to establish promising new differential diagnostic markers or target structures.

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Danksagung

Herrn Prof. Dr. med H.J. Radzun und Herrn Prof. Dr. med. P. Ströbel danke ich für ihre konsequente Unterstützung seit Beginn meiner wissenschaftlichen Karriere. Mein besonderer Dank gilt Herrn Dr. med. C.L. Behnes für die Zusammenarbeit bei unseren gemeinsamen Projekten. Darüber hinaus möchte ich Herrn PD Dr. rer. nat P. Thelen, Herrn Prof. Dr. med. S. Schweyer, Herrn Prof. Dr. rer. nat. P. Burfeind, Herrn Prof. Dr. rer nat. H. Jarry und Frau PD Dr. rer. nat S. Kaulfuß sowie Herrn PD Dr. B. Hemmerlein und Herrn PD Dr. Dr. F. Honecker für die Zusammenarbeit herzlich danken. Mein großer Dank gilt auch der Universitätsmedizin Göttingen, der Wilhelm-Sander-Stiftung (2016.041.1) sowie der Deutschen Forschungsgemeinschaft (BR 4700/1-1) für die finanzielle Unterstützung der bisherigen Projekte.

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  1. Institut für Pathologie, Universitätsmedizin Göttingen, Robert-Koch-Str. 40, 37075, Göttingen, Deutschland

    F. Bremmer

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Bremmer, F. Identifizierung von diagnostischen Tumormarkern und therapeutischen Zielstrukturen in Hodentumoren. Pathologe 39 (Suppl 2), 215–220 (2018). https://doi.org/10.1007/s00292-018-0493-z

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  • DOI: https://doi.org/10.1007/s00292-018-0493-z

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