Zusammenfassung
Hintergrund
Der Artikel gibt eine Übersicht über die Diagnostik des Ovarialkarzinoms, eine seltene, aber häufig letale Erkrankung. Die jüngste Entwicklung auf dem Gebiet hat gezeigt, dass es sich beim Ovarialkarzinom tumorbiologisch nicht um eine Erkrankung, sondern vielmehr um verschiedene Subtypen mit jeweils spezifischer Pathogenese, Morphologie, Molekularpathologie und Prognose handelt.
Methode
Der Artikel basiert auf selektiver Literaturrecherche in PubMed und gängigen pathologischen Standardwerken sowie eigener Erfahrung in Diagnostik und konsiliarpathologischer Tätigkeit am Institut für Pathologie – Charité – Universitätsmedizin Berlin.
Ergebnisse
Der häufigste histologische Subtyp ist das seröse High-grade-Ovarialkarzinom; daneben gibt es die selteneren serösen Low-grade- sowie die endometrioiden, klarzelligen und muzinösen Ovarialkarzinome. Das seröse High-grade-Adenokarzinom entsteht nach aktueller Lehrmeinung auf dem Boden eines serösen tubaren intraepithelialen Karzinoms (STIC) und ist durch eine hohe Rate an p53-Mutationen und Defekte in der homologen Rekombination gekennzeichnet.
Das seröse Low-grade-Adenokarzinom entsteht hingegen über ein Borderline-Karzinom-Kontinuum und ist molekular durch pathologische Genmutationen von KRAS oder BRAF charakterisiert. Endometrioide und klarzellige Adenokarzinome entstehen am ehesten in Zusammenhang mit einer Endometriose und weisen daher entsprechende molekulare Aberrationen der Gene wie PI3KCA, CTNNB1 und ARID1A auf. Weiterhin ist das endometrioide Adenokarzinom mit einer Mikrosatelliteninstabilität assoziiert. Der Ursprung muzinöser Ovarialtumoren ist weitestgehend unbekannt. Auch wenn ein Primarius im Gastrointestinaltrakt ausgeschlossen wird, ähneln sie morphologisch und molekular den kolorektalen Karzinomen.
Schlussfolgerung
Die molekularen Eigenheiten beeinflussen entscheidend die Prognose, den klinischen Verlauf, die Chemosensititvität und die Rezidivneigung. Translationale und klinische Studien dieses spannenden Gebiets sind notwendig, um tumorbiologische Besonderheiten herauszukristallisieren und multimodale innovative Therapiestrategien zu entwickeln.
Schlüsselwörter
Pathogenese Morphologie Molekularpathologie High-grade-Adenokarzinom Low-grade-AdenokarzinomCurrent aspects of the diagnostics of ovarian tumors
Abstract
Background
The article gives an overview of the current diagnostics of ovarian cancer, a rare but often fatal disease. The most recent development in this field has shown that from the tumor biology, ovarian cancer is not one disease but different subtypes each with a specific pathogenesis, morphology, molecular pathology and prognosis.
Methods
The article is based on a selective literature search in PubMed and standard pathological reference works as well as own experiences in diagnostics and consultative pathology at the Institute of Pathology, Charité, Medical University of Berlin.
Results
The most common histological subtype is high-grade serous ovarian carcinoma and in addition there are the rarer low-grade serous, endometrioid, clear cell and mucinous ovarian carcinomas. According to the current scientific consensus, the high-grade serous adenocarcinoma develops from a serous tubal intra-epithelial carcinoma (STIC) and is characterized by a high rate of p53 mutations and defects in the homologous recombination. By contrast, the low-grade serous adenocarcinoma arises from a borderline to carcinoma continuum and is molecularly characterized by pathological gene mutations in KRAS or BRAF. Endometrioid and clear cell adenocarcinomas are most likely associated with endometriosis and therefore have corresponding molecular aberrations of genes, such as PI3KCA, CTNNB1 and ARID1A. Furthermore, endometrioid adenocarcinomas are associated with microsatellite instability. The origin of mucinous ovarian tumors is largely unknown. Even if a primary tumor in the gastrointestinal tract is excluded, they are morphologically and molecularly similar to colorectal carcinomas.
Conclusion
These molecular characteristics influence the prognosis, clinical course, chemosensitivity and the tendency to recurrence. Translational and clinical studies in this exciting field are necessary to understand specific biological tumor characteristics and to develop multimodal innovative therapeutic strategies.
Keywords
Pathogenesis Morphology Molecular pathology High-grade serous ovarian carcinoma Low-grade serous adenocarcinomaNotes
Einhaltung ethischer Richtlinien
Interessenkonflikt
E.T. Taube, I. Braicu, C.A. Kunze, H. Kulbe, W.D. Schmitt und C. Denkert geben an, dass kein Interessenkonflikt besteht.
Dieser Beitrag beinhaltet keine von den Autoren durchgeführten Studien an Menschen oder Tieren.
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