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Apoptose und Tumorregression bei neoadjuvant behandelten lokal fortgeschrittenen nichtkleinzelligen Lungenkarzinomen

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Zusammenfassung

Fehler im Prozess der Apoptoseregulation sind eng mit einer malignen Zelltransformation assoziiert. Andererseits wird die Apoptose durch Zytostatika und Strahlentherapie induziert. Vor diesem Hintergrund wurden bei 54 neoadjuvant behandelten lokal fortgeschrittenen nichtkleinzelligen Lungenkarzinomen (NSCLC; 36 Plattenepithel-, 18 Adenokarzinome, Stadium IIIA/IIIB) die Apoptoseraten (TUNEL-Methode) vor Einleitung und nach Abschluss der Behandlung vergleichend analysiert und mit dem Ansprechen auf die neoadjuvante Therapie (Grad der therapieinduzierten Tumorregression) sowie den Überlebenszeiten korreliert. Dabei ließ sich ein statistisch signifikanter Unterschied zwischen prä- und posttherapeutisch ermittelten Apoptoseindices nicht nachweisen (arithmetische Mittelwerte: 0,93% vs. 1,1%). Ein signifikant prädiktiver Wert der Höhe der Apoptoseindices konnte weder prä- noch posttherapeutisch im Hinblick auf Unterschiede im Gesamtüberleben aufgezeigt werden. Eine statistisch signifikante Abhängigkeit der bestimmten Apoptoseindices vom Regressionsgrad ließ sich weder prä- noch posttherapeutisch belegen. Diese Resultate verdeutlichen, dass eine neoadjuvante Therapie die Apoptoserate bösartiger Lungentumoren nicht langfristig modifiziert. Dies trägt bereits wenige Wochen nach Abschluss der neoadjuvanten Chemo- und Radiotherapie zu einem Nettoproliferationsverhalten des Resttumorgewebes bei, das weitgehend dem des unbehandelten Tumors entspricht.

Abstract

Dysregulation of apoptosis is closely associated with malignant cell transformation. On the other hand, apoptosis is induced by chemotherapy or irradiation. Therefore, in 54 patients with locally advanced non-small cell lung cancer (NSCLC, 36 squamous cell carcinomas, 18 adenocarcinomas, stage IIIA/IIIB), apoptotic indices were comparatively analysed before onset and after termination of neoadjuvant therapy. The results were compared with the response to neoadjuvant therapy (extent of therapy-induced tumour regression) as well as the survival times. A statistically significant difference could not be established between pre-therapeutically and post-surgically established apoptotic indices (mean values: 0.93% vs. 1.1%). Neither before therapy nor after surgery did the apoptotic indices show a significant predictive value concerning different overall survival times. These results suggest that neoadjuvant therapy does not modify the extent of apoptosis in lung cancer in the long term. Only a few weeks after the completion of the neoadjuvant chemoradiotherapy this contributes to a net proliferation of the residual tumour tissue which is largely equivalent to that of the untreated tumour.

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Authors and Affiliations

  1. Institut für Pathologie, Universitätsklinik Bergmannsheil, Bochum

    K. Junker & K.-M. Müller

  2. , Institut für Pathologie, Osnabrück

    U. Bosse

  3. Thoraxchirurgie, St. Raphael-Hospital, Ostercappeln

    F. Klinke

  4. Institut für Medizinische Informatik und Biomathematik, Westfälische Wilhelms-Universität, Münster

    A. Heinecke

  5. Medizinische Klinik A, Westfälische Wilhelms-Universität, Münster

    M. Thomas

  6. Institut für Pathologie, BG-Kliniken Bergmannsheil – Klinikum der Ruhr-Universität Bochum, Bürkle-de-la-Camp-Platz 1, 44789, Bochum

    K. Junker

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  1. K. Junker
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  2. K.-M. Müller
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  3. U. Bosse
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  4. F. Klinke
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  5. A. Heinecke
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  6. M. Thomas
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Correspondence to K. Junker.

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Junker, K., Müller, KM., Bosse, U. et al. Apoptose und Tumorregression bei neoadjuvant behandelten lokal fortgeschrittenen nichtkleinzelligen Lungenkarzinomen. Pathologe 24, 214–219 (2003). https://doi.org/10.1007/s00292-002-0607-4

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  • DOI: https://doi.org/10.1007/s00292-002-0607-4

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