Prognostischer Wert von Zelloberflächenmolekülen bei kolorektalen Karzinomen

Zusammenfassung.

Etwa ein Drittel der Patienten mit kolorektalen Karzinomen versterben infolge ihres Tumorleidens. Obwohl Fortschritte in der chirurgischen und adjuvanten Behandlung kolorektaler Karzinome zu verbesserten Überlebensraten bei Patienten mit frühen Stadien geführt haben, konnten bei mehr fortgeschrittenen Stadien noch keine durchgreifenden Verbesserungen des Überlebens der Patienten erreicht werden. Es ist jedoch zu erwarten, dass die Selektion von Patienten für aggressive Therapien auf der Basis einer Prognosebewertung und anderer Charakteristika zu größeren Erfolgen adjuvanter Therapien bei Patienten mit Dukes-B- oder C-Karzinomen führt. Bisherige Untersuchungen haben gezeigt, dass die Expression von Oberflächenmolekülen auf kolorektalen Tumorzellen eng mit maligner Transformation, Tumorprogression und/oder Patientenprognose verbunden ist. Unter diesen Zelloberflächenmolekülen erscheinen verschiedene Adhäsionsmoleküle als potenziell nützliche prognostische oder prädiktive Marker. Obwohl zahlreiche Studien über deren prognostischen und prädiktiven Wert existieren, sind multivariate Analysen zur Identifizierung prognostisch relevanter Faktoren in kolorektalen Tumorzellen nur in sehr begrenztem Umfang verfügbar. Des Weiteren haben bisherige Studien die Heterogenität innerhalb der Tumoren und damit in Zusammenhang stehende Varianz der Expression von zellulären Strukturen nur unzureichend berücksichtigt. Am erfolgversprechendsten erscheinen derzeit β1-, β4-, α6-Integrine, E-Cadherin und seine intrazellulären Partnerproteine α-, β-Catenin, CD44-v6 und andere Splice-Varianten, Sialyl-Lewis^x, Karzinoembryonales Antigen sowie Von-Willebrand-Faktor. Allerdings ist eine abschließende Bewertung bisher für keinen dieser Parameter möglich. In zukünftigen Studien müssen unter Nutzung reproduzierbarer und standardisierter Verfahren und unter Berücksichtigung der intratumoralen Heterogenität multivariate Analysen von Oberflächenmarkern, wie z. B. Adhäsionsmolekülen, in kolorektalen Karzinomen in ausreichend großen Patientenkollektiven hinsichtlich ihrer biologischen und prognostischen Relevanz und potenzieller Nutzbarkeit für therapeutisches Management untersucht werden.

Prognostic value of cell adhesion molecules in colorectal carcinomas.

About one third of patients with colorectal carcinomas are dying because of their tumor-related problems. Advances in the primary treatment of these patients during the last two decades resulted in increased survival and better prognosis at early tumor stages, but patients with more advanced stages of colorectal cancer have still poor prognosis. However, patients with Dukes B or C carcinomas may benefit from better selection of patient subgroups based on their prognosis and other characteristics for adjuvant treatment. Recent investigations demonstrated that the expression of cell surface molecules on colorectal carcinoma cells is closely related to malignant transformation, tumor progression and/or patient prognosis. Numerous studies about their prognostic relevance are published; however, multivariate analysis for identification of relevant prognostic markers are uncommon. Additionally, remarkable heterogeneity within the tumors has been shown including varaible expression of cellular structures which is not considered in most studies. Currently, β1-, β4-, α6-integrins, E-cadherin and its intracellular partner- protein α-, β-catenin, CD44-v6 and other splice-Variants, sialyl-Lewis^x, carcinoembrionic antigen, and von Willebrand-Faktor appear to be potentially useful as prognostic markers. However, final evaluation remains necessary for all parameters. Using reproducible and standardized procedures and multivariate analysis future studies should investigate cell surface proteins, such as adhesion molecules, for their biological and prognostic relevance in sufficient numbers of patients. These investigations should also consider intratumoral heterogeneity to identify parameter that can be used for clinical management of colorectal cancer patients.

Schlüsselwörter:

Zelladhäsionsmoleküle - Kolorektale Karzinome - Prognose - Prädiktiver Wert

Key words:

Cell adhesion molecules - Colorectal carcinoma - Prognosis - Predictive value

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