Genotypisierung von disseminierten epithelialen Zellen bei Mammakarzinom-Patientinnen

Zusammenfassung

Der Nachweis von disseminierten epithelialen Zellen im Knochenmark (KM) und Blut von Mammakarzinom-Patientinnen ist mit einer schlechten Prognose assoziiert. Jedoch haben Langzeitstudien gezeigt, dass nicht alle diese Patientinnen eine Fernmetastasierung erleiden. Daher ist über die reine Detektion hinaus die weiter gehende Charakterisierung disseminierter epithelialer Zellen zum Malignitätsnachweis und zur Prognoseabschätzung notwendig. Immunzytochemische Doppelfärbungen haben bereits viel dazu beigetragen, die Bedeutung dieser Zellen besser zu verstehen. Mittlerweile sind auch Genotypisierungen mittels Interphase-Fluoreszenz-in-situ-Hybridisierung (Interphase-FISH) möglich. Disseminierte epitheliale Zellen weisen zahlreiche chromosomale numerische Aberrationen auf. Des Weiteren konnten Amplifikationen für einzelne Gene, wie HER2 und MYC, detektiert werden. Die Genotypisierung kann somit über den Nachweis numerischer Aberrationen dazu beitragen, den malignen Charakter der epithelialen Zellen im Blut und Knochenmark zu beschreiben und zu bestätigen. Des Weiteren erlaubt die FISH-Analyse mit locusspezifischen DNA-Sonden (HER2, MYC) das tumorbiologische Verhalten der epithelialen Zellen besser einzuschätzen. Die Genotypisierung wird in Zukunft zur weiter gehenden Charakterisierung der disseminierten Tumorzellen verstärkt ihren Einsatz finden.

Abstract

The presence of disseminated epithelial cells in bone marrow of breast cancer patients is associated with poor prognosis. However, even during long-term follow-up not all of these patients will develop metastatic disease. Therefore, further characterization of disseminated epithelial cells is necessary to determine their malignant potential. Immunocytochemical double-staining was used in the majority of studies to get a better understanding of these cells. Recently, genotyping of disseminated tumor cells by interphase FISH has been established as a further tool to study the role of these cells in more detail. Using FISH technology, numerical aberrations for a variety of chromosomes were discovered in disseminated epithelial cells. Moreover, several studies demonstrated HER2 and MYC amplification in disseminated tumor cells.

These preliminary data suggest that genotyping can be used to describe and confirm the malignant nature of disseminated tumor cells. Moreover, the tumorbiological role of these epithelial cells can be studied in more detail by locus-specific probes for HER2 or MYC. Genotyping of tumor cells by interphase-FISH will become an important tool to characterize disseminated tumor cells.

Tumorzelldisseminierung - FISH - Mammakarzinom - Genotypisierung

Tumor cell dissemination - FISH - breast cancer - genotyping

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