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Neuroendokrine Differenzierung im Prostatakarzinom

Ein Marker für die Androgen- und Strahlenresistenz

Neuroendocrine differentiation in prostate cancer: an unrecognized and therapy resistant phenotype

  • Schwerpunkt: Prostatapathologie
  • Published:
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Zusammenfassung

Das gewöhnliche Adenokarzinom der Prostata besteht überwiegend aus exokrinen (PSA-produzierenden) Tumorzellen. Daneben finden sich neuroendokrine (NE) Tumorzellen, die nahezu in allen Prostatakarzinomen (PCa) vorkommen. Der NE-Phänotyp wird meist erst immunhistochemisch (Chromogranin A) erkannt. Zellbiologische und klinische Daten sprechen für die Androgen- und Strahlenresistenz der NE-Tumorzellen im gewöhnlichen Prostatakarzinom.

Die NE-Tumorzellen befinden sich in der G0-Phase des Zellzyklus und sind weitgehend resistent gegenüber dem programmierten Zelltod. Sie entstehen über einen Prozess der intermediären Differenzierung aus dem exokrinen Tumorzelltyp. Den NE-Tumorzellen fehlt der Androgenrezeptor (AR), sie produzieren aber eine Reihe von hormonellen Wachstumsfaktoren, die die Proliferationsaktivität in benachbarten, exokrinen Tumorzellen über parakrine (androgenunabhängige) Regulationsmechanismen beeinflussen können.

Die NE-Tumorzellen bilden somit eine androgeninsensitive Zellpopulation im Prostatakarzinom und sind als G0-Zellen relativ strahlenresistent und potenziell unsterblich. In der klinischen und histopathologischen Routinediagnostik sollte gezielt nach der NE-Differenzierung gefahndet werden, wenn für den Patienten die Option auf eine Androgenentzugs- bzw. Strahlentherapie besteht.

Abstract

Neuroendocrine (NE) differentiation frequently occurs in common prostatic malignancies but usually escapes pathological and clinical detection. The present review focuses on biological properties of NE tumor cells making them resistant to androgen deprivation and radiation therapy. Recent data have shown that NE prostate cancer cells (as defined by the most commonly used endocrine marker chromogranin A) are arrested in the G0-phase of the cell cycle and do not undergo apoptosis. This particular phenotype consistently lacks the nuclear androgen receptor in both benign and malignant conditions but produces a series of hormonal growth factors exerting mitogenic stimuli on adjacent, exocrine tumor cells.

Neoplastic NE cells devoid of the nuclear androgen receptor constitute an androgen-insensitive cell population in prostate cancer. The absence of proliferative and apoptotic activity makes NE tumor cells particularly resistant towards cytotoxic drugs and radiation therapy. Pathological and clinical detection of NE features is recommended for all prostate cancer patients for whom radiation therapy and androgen deprivation is being considered.

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Mit freundlicher Unterstützung durch die Deutsche Forschungsgemeinschaft, Bo 1018/2–3.

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  1. Praxis für Pathologie, Berlin

    H. Bonkhoff

  2. Fraunhofer Institut für Biomedizinische Technik, St. Ingbert

    T. Fixemer

  3. Praxis für Pathologie, Tietzenweg 129, 12203, Berlin

    H. Bonkhoff

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  1. H. Bonkhoff
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  2. T. Fixemer
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Correspondence to H. Bonkhoff.

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Bonkhoff, H., Fixemer, T. Neuroendokrine Differenzierung im Prostatakarzinom. Pathologe 26, 453–460 (2005). https://doi.org/10.1007/s00292-005-0791-0

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  • DOI: https://doi.org/10.1007/s00292-005-0791-0

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