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TumorDiagnostik & Therapie 2003; 24(1): 21-25
DOI: 10.1055/s-2003-37563
Übersicht/Review
© Georg Thieme Verlag Stuttgart · New York

Tumor Cell Dissemination in Solid Tumors: Clinical Usefulness of Diagnostic Approaches, Prognostic Significance, and Therapeutical Options

Tumorzelldisseminierung in soliden Tumoren: Durchführbarkeit der diagnostischen Fortschritte, Prognostik und therapeutische MöglichkeitenS.  Kasimir-Bauer1
  • 1Innere Klinik und Poliklinik (Tumorforschung), Universitätsklinik Essen, 45122 Essen
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Publication History

Publication Date:
03 March 2003 (online)

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Zusammenfassung

Auch nach vollständiger Entfernung des Primärtumors und fehlendem Nachweis einer Metastasierung mit konventionellen diagnostischen Verfahren zu diesem Zeitpunkt besteht für eine Vielzahl von Karzinompatienten ein deutliches Risiko, Fernmetastasen zu entwickeln. Diese Fernrezidive sind nach dem heutigen Kenntnisstand auf disseminierte Tumorzellen zurückzuführen, die sich frühzeitig vom Primärtumor gelöst haben, sich in anderen Organen ansiedeln und dort zum Ausgangspunkt einer Metastase werden können. Da diese Zellen bisher weder durch hochauflösende bildgebende Diagnoseverfahren noch durch die klassische Histopathologie nachweisbar sind, wurden in den letzten Jahren sensitive immunzytochemische und molekulare Methoden entwickelt, die den Nachweis von einer Tumorzelle unter 1 × 106 normalen Zellen ermöglichen. Obwohl das Vorliegen dieser Zellen - z. B. im Knochenmark als Indikatororgan - in einer Reihe von Tumoren epithelialer Herkunft nachgewiesen wurde, und als relevanter Prognosefaktor angesehen wird, variieren die Ergebnisse einzelner Studien durch die Verwendung verschiedener Antikörper und unterschiedlich sensitiver Testsysteme, was einen Vergleich der Studien erschwert. Eine allgemeingültige Methodik zum Nachweis und zur Charakterisierung disseminierter Zellen gibt es zurzeit noch nicht. Obwohl die Immunzytochemie unter Verwendung von Antikörpern gegen Zytokeratine als Zellgerüst epithelialer Zellen zur Zeit am häufigsten Anwendung findet, gibt es auch hier kritische Variablen, die standardisiert werden müssen, um den Nachweis disseminierter Tumorzellen in die klinische Routine zu integrieren. Dieser Artikel gibt einen Überblick über methodische Aspekte zum Nachweis und zur Charakterisierung disseminierter Tumorzellen von soliden Tumoren im Hinblick auf die Durchführbarkeit dieser Techniken im klinischen Alltag, die klinische Relevanz und mögliche Therapieoptionen.

Abstract

Besides early detection and surgical therapy of the primary tumor, mortality from solid malignant tumors has remained high and even in modern chemoradiation protocols a high number of carcinoma patients experiences tumor recurrences. The major reason for relapse is the hematogeneous or lymphatic spread of occult tumor cells which can arise before diagnosis of primary tumor growth at an early stage and which is regularly underestimated by currently available clinical and pathologic staging procedures. To improve the diagnosis of the occult stage of early metastases, sensitive immunohistochemical and molecular techniques were developed to facilitate the detection of isolated carcinoma cells in mesenchymal organs like bone marrow or lymph nodes using monoclonal antibodies against epithelium-specific proteins. Several studies demonstrated that the detection of isolated disseminated tumor cells in the bone marrow is an independent prognostic variable in breast, colorectal, gastric, and non-small-cell lung cancer but the comparison of the results becomes difficult due to lack of a standardized protocol. At present immunocytochemistry, using antibodies targeting a broad number of cytokeratins, with a sensitivity of one carcinoma cell among one million mononuclear bone marrow cells, seems to be the method of choice. But there are still some variables which have to be standardized to integrate the detection and characterization of disseminated tumor cells in clinical routine. The present review focuses on methodological aspects for identification and characterization of tumor cells, the clinical relevance of diagnostic approaches with their impact on treatment of minimal residual disease.

Schlüsselwörter

Solide Tumoren - Tumorzelldisseminierung - Knochenmark - Blut - Lymphknoten - Zytokeratine - Immunzytochemie

Key words

Solid tumors - tumor cell dissemination - bone marrow - blood - lymph nodes - cytokeratins - immunocytochemistry

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Dr. rer. nat. Sabine Kasimir-Bauer

Innere Klinik und Poliklinik (Tumorforschung), Universitätsklinikum Essen

Hufelandstraße 55

45122 Essen

Phone: (+49) 201-723-3112

Fax: (+49) 201/723-5736

Email: sabine.kasimir-bauer@uni-essen.de

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