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Minimalresiduale Tumorerkrankung bei gastrointestinalen Karzinomen

Prognoserelevanz und onkologisch-chirurgische Konsequenzen

Minimal residual tumor in gastrointestinal carcinoma

Relevance to prognosis and oncologic surgical consequences

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Zusammenfassung

Isolierte Tumorzellen (ITZ) als Ausdruck einer „minimal residuellen Tumormanifestation“ (MRD) entziehen sich in der Regel der perioperativen Routinediagnostik. Tatsächlich sind sie aber relativ oft in Lymphknoten, in der Peritonealhöhle, im Blut oder im Knochenmark präsent. Dies bedeutet ein permanentes Understaging von Tumorpatienten, begründet unerwartete Tumorrezidive nach vermeintlich kurativer Therapie und unterstreicht die Bedeutung dieser Zellen zumindest als Surrogatparameter. Die Häufigkeit des Auftretens der ITZ in den verschiedenen Körperbereichen hängt von der Primärtumorart ab. Die bisher konsekutiv entwickelten Nachweismethoden werden zunehmend sensitiver, jedoch häufig auf Kosten der Spezifität. Als bewiesen kann die Lebensfähigkeit der ITZ und ihre mögliche Tumorigenität angesehen werden. Allerdings konnte auch eine ausgesprochene Heterogenität der ITZ im Hinblick auf Proliferation und Tumorigenität und die damit in Zusammenhang stehende Expression verschiedener Gene gezeigt werden. Leider besteht auch eine Heterogenität bei der Gewinnung, den Nachweismethoden und der Aufarbeitung dieser Zellen. Trotz aller zurzeit berechtigten Kontroversen hinsichtlich des Nachweises und der biologischen Bedeutung von MRD/ITZ ist zumindest eine mögliche prognostische Relevanz auch unter multivariater Testung bei gastrointestinalen Karzinomen nicht von der Hand zu weisen. Diese Ergebnisse sollten daher zukünftig in der Planung chirurgisch-onkologischer Studien zumindest als Stratifizierungsmerkmal vermehrt Beachtung finden.

Abstract

Isolated tumor cells as a consequence of minimal residual disease are often not detectable by routine diagnostic procedures. However, before or after surgery, isolated tumor cells in lymph nodes, the peritoneal cavity, blood, or bone marrow can frequently be identified by immunohistochemical or molecular methods. Failure to reveal the presence of such cells results in understaging of tumor patients and may constitute the source of unexpected tumor recurrence after radical surgery. These facts emphasize the importance of isolated tumor cells at least as a surrogate marker. The frequency of appearance of isolated tumor cells in different organ systems also depends on the type of primary tumor. Developments in modern detection methods have led to increasing sensitivity but at the expense of specificity. Isolated tumor cells demonstrate remarkable heterogeneity with respect to proliferative potential and tumorigenicity. This characteristic is also reflected by a striking variability in the expression of various genes conditioning the aforementioned biological behavior. Unfortunately there is also remarkable heterogeneity in methods used for sampling and processing patient material as well as for the enrichment and detection of isolated tumor cells. Despite the ongoing controversies concerning detection methods and biological significance of isolated tumor cells, several clinical trials providing data supporting the prognostic relevance of minimal residual disease should also be considered for gastrointestinal carcinoma. In future this finding should be integrated in the planning of trials in surgical oncology, and “minimal residual disease” should receive stronger attention as a stratification criterion in such clinical studies.

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  1. Klinik für Chirurgie und Chirurgische Onkologie, Robert-Rössle-Klinik am Helios Klinikum Berlin, Universitätsmedizin Berlin, Charite Campus Buch, Lindenberger Weg 80, 13125 , Berlin

    S. Gretschel, A. Bembenek, T. Schulze, W. Kemmner &  P. M. Schlag

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  1. S. Gretschel
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  2. A. Bembenek
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Gretschel, S., Bembenek, A., Schulze, T. et al. Minimalresiduale Tumorerkrankung bei gastrointestinalen Karzinomen. Chirurg 77, 1104–1117 (2006). https://doi.org/10.1007/s00104-006-1263-7

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