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Lasermikrodissektion und molekulare Charakterisierung von dysplastischen Zellen aus Zervixabstrichen

Ein neues analytisches Konzept zur Frühdiagnose des Zervixkarzinoms

Laser microdissection and molecular typing of dysplastic cells from Pap smears: a new approach to early detection of cervical cancer

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Zusammenfassung

Wissensstand.

Der Papanicolaou-Test dient weltweit zum Screening auf Zervixkarzinom und dessen Vorläuferläsionen. Die Transition von Dysplasie zu Krebs jedoch ist ein komplexer genetischer Prozess und kann nicht allein anhand morphologischer Kriterien vorhergesagt werden.

Fragestellung.

Kann die molekulare Charakterisierung dysplastischer Zellen aus Zervixabstrichen zur besseren Definition von Hochrisikoläsionen mit Progressionspotenzial beitragen?

Ziele.

Entwicklung einer Methode, die morphologische Begutachtung und molekulare Multiparameteranalyse dysplastischer Zellen aus Zervixabstrichen vereint.

Methoden und Ergebnisse.

Dysplastische Zellen aus 52 nach Papanicolaou gefärbten Zervixabstrichen unterschiedlicher Klassifikationen wurden mittels Lasermikrodissektion isoliert und auf zervixkarzinomtypische DNA-Läsionen untersucht. Der in Zervixkarzinomgewebe beschriebene „loss of heterozygosity“ (LOH) wurde von uns nachgewiesen. Die Marker früher Stadien zeigten einen LOH in 43% bzw. 22%, diejenigen später Stadien in 26% der Analysen.

Fazit.

Die Kombination morphologischer Begutachtung und molekularer Multiparameteranalyse dysplastischer Zellen aus Zervixabstrichen eröffnet weitere diagnostische Möglichkeiten in der Frühdetektion des Zervixkarzinoms.

Abstract

The Papanicolaou smear (Pap) is a worldwide screening tool for early detection of cervical cancer and its precursor lesions. The transition from dysplasia to cancer is a highly complex genetic process and cannot be predicted based solely on cell morphology. Molecular characterization of precursor lesions could yield a better definition of lesions at high risk for progression.

We developed an analytical concept comprising not only morphological characterization but also molecular analysis with multiple parameters of dysplastic cells from cervical smears.

We isolated dysplastic cells from 52 fixed Pap-stained smears of various grades by laser microdissection and analyzed them for genetic lesions typical for cervical carcinoma. The loss of heterozygosity (LOH) as published for cervical carcinoma tissue was detected. Markers for early stages showed a LOH in 43% and 22%, and those for late stages in 26% of the cases.

Combining morphological characterization with molecular analysis by multiple molecular markers could open up new opportunities for early detection of cervical carcinoma.

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Danksagung

Unser Dank gilt Frau Sabine Pomphrey für ihre Assistenz im Bereich Zytologie.

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Eder, C., Chaganti, R.S.K., Murty, V.V.V.S. et al. Lasermikrodissektion und molekulare Charakterisierung von dysplastischen Zellen aus Zervixabstrichen. Pathologe 25, 209–216 (2004). https://doi.org/10.1007/s00292-003-0663-4

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  • DOI: https://doi.org/10.1007/s00292-003-0663-4

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