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Molekularpathologie der epithelialen Ovarialneoplasien

Von der Phänotyp-Genotyp-Korrelation zu neuen Ansatzpunkten in Diagnostik und Therapie

Molecular pathology of epithelial ovarian neoplasias: from the phenotype-genotype correlation to new targets in diagnostics and therapy

  • Schwerpunkt: Ovarialtumoren
  • Published:
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Zusammenfassung

Trotz großer morphologischer Vielfalt lassen sich bei Ovarialkarzinomen aufgrund von pathogenetischen Gemeinsamkeiten 2 Gruppen unterscheiden. In der Zusammenschau von klinischen, pathologischen und molekularen Parametern zeigt sich einerseits eine relativ große Gruppe von Tumoren mit schrittweiser Entstehung aus gutartigen Vorstufen über Borderline-Tumoren hin zu invasiven Karzinomen (Typ I). Je nach morphologischem Typ kommen dabei unterschiedliche Genveränderungen zum Tragen. Dazu gehören Mutationen in KRAS und BRAF in serösen Borderline-Tumoren und „low grade“ serösen Karzinomen. Mutationen in KRAS finden sich auch häufig in muzinösen Borderline-Tumoren und muzinösen Karzinomen. Bei endometrioiden Tumoren findet man vor allem Mutationen in Komponenten der Wnt-Signalkaskade, in PTEN oder in Genen, welche eine Gruppe von Proteinen für DNA-Reparaturmechanismen kodieren („mismatch repair“). Zur zweiten, größeren Gruppe (Typ II) gehören Tumoren mit De-novo-Entstehung von hochmalignen Karzinomen. Hierbei handelt es sich zumeist um die konventionellen, mäßig bis gering differenzierten serösen Karzinome und undifferenzierte Karzinome. Diese sind insbesondere durch häufige Mutationen von p53 und komplexe chromosomale Alterationen gekennzeichnet. Es ist zu erwarten, dass kombinierte Analysen von morphologischen Parametern, genetischen Veränderungen, Genexpressions- und Proteinmustern in diesen beiden Gruppen von Tumoren neue Ansatzpunkte für Diagnostik und Therapie identifizieren werden.

Abstract

Despite the fact that ovarian carcinomas are phenotypically heterogeneous, they can be divided into two main groups with common pathogenetic mechanisms. Based on clinical, pathological and molecular parameters, a relatively large group of tumors can be distinguished with stepwise development from benign precursors and borderline tumors to invasive carcinomas (type I). Depending on the morphological phenotype, characteristic genetic changes can be observed, such as mutations in KRAS and BRAF in serous borderline tumors and low-grade serous carcinomas. Mutations in KRAS are also frequently detected in mucinous borderline tumors and mucinous carcinomas. The group of endometrioid tumors is characterized by mutations in components of the Wnt-signal transduction pathway and PTEN or microsatellite instability. The second large group of tumors (type II) includes tumors with “de novo” development of highly malignant carcinomas such as the conventional (moderately to poorly differentiated) high-grade serous carcinomas, undifferentiated carcinomas and malignant mixed mesodermal tumors. These tumors are associated with frequent mutations in p53 and complex chromosomal alterations. In the future, the combined analysis of morphological parameters, genetic changes, gene-expression profiling and protein data will reveal possible diagnostic and therapeutic targets for ovarian carcinomas.

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  1. Institut für Pathologie, Westfälische Wilhelms-Universität, Domagkstraße 17, 48149, Münster, Deutschland

    A. Staebler

  2. Pathologisches Institut der Ludwig-Maximilians-Universität, München, Deutschland

    J. Diebold

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  2. J. Diebold
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Correspondence to A. Staebler.

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Staebler, A., Diebold, J. Molekularpathologie der epithelialen Ovarialneoplasien. Pathologe 28, 180–186 (2007). https://doi.org/10.1007/s00292-007-0910-1

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