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Zentralbl Gynakol 2001; 123(4): 192-197
DOI: 10.1055/s-2001-14779
Historisches, Pathogenese und Epidemiologie

J.A.Barth Verlag in Medizinverlage Heidelberg GmbH & Co.KG

Hypoxie beim Zervixkarzinom: Pathogenese, Charakterisierung und biologische/klinische Konsequenzen [1]

Tumor hypoxia in cervical cancer: Pathophy-sociological aspects, clinical evidence and consequencesP. Vaupel1 , M. Höckel2
  • 1Institut für Physiologie und Pathophysiologie, Universität Mainz (Direktor: Prof. Dr. M. Vaupel)
  • 2Universitätsfrauenklinik (Triersches Institut), Universität Leipzig (Direktor: Prof. Dr. M. Höckel)
Further Information

Publication History

Publication Date:
31 December 2001 (online)

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Zusammenfassung

Lokal fortgeschrittene Zervixkarzinome weisen in der Mehrzahl (ca. 60 %) hypoxische und anoxische Gewebeareale auf. Die heterogen über den Tumor verteilten Hypoxiebereiche sind Folge struktureller Anomalien der neu gebildeten Tumorgefäße, einer gestörten Durchblutung, vergrößerter Diffusionswege und einer tumor- bzw. therapieassoziierten Anämie. Das Ausmaß der prätherapeutischen Hypoxie ist unabhängig von der klinischen Größe, dem Stadium und dem Differenzierungsgrad des Tumors. Anämie verstärkt die Tumorhypoxie. Vergleicht man den prätherapeutischen Oxygenierungsstatus in Zervixkarzinomen gleichen Stadiums und Differenzierungsgrades, so zeigen sich erhebliche inter-individuelle Unterschiede. Die in Beckenrezidiven gemessenen O2-Druckwerte sind deutlich niedriger als in den Primärtumoren. Etwa 78 % der Lokalrezidive weisen Hypoxieareale auf. Die Existenz hypoxischer Tumorbereiche beeinträchtigt sowohl direkt als auch indirekt (u. a. über Zellzykluseffekte) die Effizienz der Therapie mit schwach-ionisierenden Strahlen und einer Reihe O2-abhängiger Zytostatika. Weiterhin kann die Tumorhypoxie die maligne Progression fördern. Dies erklärt die bedeutende Rolle der Tumorhypoxie als unabhängiger, aussagekräftiger Prognoseparameter für die Lokalkontrolle und Überlebensrate. Darüber hinaus könnte die routinemäßige Erfassung des prätherapeutischen Oxygenierungsstatus Möglichkeiten einer von anderen onkologischen Parametern unabhängigen individuellen Therapieplanung eröffnen.

Tumor hypoxia in cervical cancer: Pathophy-sociological aspects, clinical evidence and consequences

Summary

Approximately 60 % of locally advanced carcinomas in the uterine cervix exhibit hypoxic and/or anoxic tissue areas which are heterogeneously distributed within the tumor mass. Hypoxia is caused by structural and functional abnormalities of the newly formed tumor vessels arising from neovascularization, by a disturbed microcirculation, enlarged diffusion distances and by tumor- or therapy-associated anemias. The extent of pretherapeutically measured hypoxic tissue areas is independent of clinical size, FIGO stage and histopathological grade of squamous cell carcinomas of the uterine cervix. Anemia can intensify tumor hypoxia. O2-tensions in local recurrences are even lower than those in the primary tumors. About 78 % of recurrent tumors exhibit hypoxic tissue areas. Hypoxia is known to directly or indirectly (e. g., via cell cycle effects) affect the therapeutic efficacy of sparsely ionizing radiation and some forms of chemotherapy. Sustained tissue hypoxia may also cause molecular changes that can result in a more malignant phenotype, a process termed malignant progression. Based on this association between tumor hypoxia and malignant progression, tumor oxygenation has proven to be an independent, powerful prognostic factor of local control, overall and disease-free survival. In addition, the routine evaluation of the pretherapeutic oxygenation status may enable individual therapeutic strategies, independent of other oncologic parameters.

Schlüsselwörter

Zervixkarzinom - Oxygenierungsstatus - Hypoxie - maligne Progression - Therapieresistenz - Prognosefaktor

Key words

Carcinoma of the uterine cervix - oxygenation status - hypoxia - malignant progression - therapy resistance - prognostic factor

1 Gefördert durch die Deutsche Krebshilfe (70-1920 Va 2)

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1 Gefördert durch die Deutsche Krebshilfe (70-1920 Va 2)

Univ.-Prof. Dr. med. Peter VaupelM.A./Univ. Harvard 

Institut für Physiologie und Pathophysiologie
Universität Mainz

Duesbergweg 6

D-55099 Mainz