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Der prädiktive Wert der PD-L1-Diagnostik

Predictive value of PD-L1 diagnostics

  • Schwerpunkt: Immunpathologie
  • Published:
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An Erratum to this article was published on 29 May 2019

This article has been updated

Zusammenfassung

Immunonkologische Therapien sind mittlerweile Standardbehandlungen für mehrere Tumorentitäten geworden. Viele weitere Indikationen werden zurzeit in klinischen Therapiestudien erforscht. Unter mehreren Biomarkern, wie z. B. Mikrosatelliteninstabilität oder Tumormutationslast, hat sich die Bestimmung der PD-L1(„programmed cell death ligand 1“)-Expression im Tumorgewebe bislang am stärksten in der klinischen Anwendung etabliert. Die PD-L1-Immunhistochemie ist ein obligatorischer prädiktiver Biomarker für bestimmte immunonkologische Behandlungskonzepte beim nichtkleinzelligen Lungenkarzinom, bei Urothelkarzinomen und Kopf-Hals-Karzinomen. Es ist zu erwarten, dass in naher Zukunft weitere Therapien bei Magen- oder Zervix-Karzinomen auch in Europa zugelassen werden, die ebenfalls eine PD-L1-Testung erforderlich machen. Außerdem kann die PD-L1-Bestimmung als fakultativer Biomarker für klinische Entscheidungen hilfreich sein. Die PD-L1-Testung erfordert eine sensitive Immunfärbung über einen breiten dynamischen Bereich mit geeigneten Primärantikörpern und abgestimmten Färbeprotokollen. Für die Auswahl des Untersuchungsmaterials sowie für die Validierung und die fortlaufende Qualitätskontrolle der Färbung sind hohe Standards anzulegen. Die Auswertung erfolgt nach verschiedenen Auswertealgorithmen. Während der TPS („tumor proportion score“) ausschließlich membranäre Färbungen in Tumorzellen bewertet, berücksichtigen CPS („combined positivity score“) und IC-Scoring („immune cell“) auch oder ausschließlich PD-L1-Färbungen in bestimmten Immunzellen. TPS wird vorrangig bei nichtkleinzelligen Lungenkarzinomen, Melanomen und Karzinomen der Kopf-Hals-Region eingesetzt, CPS und IC-Scoring sind Standarduntersuchungen bei Urothelkarzinomen.

Abstract

Immuno-oncology related treatments have become standard of care for many tumor entities. Numerous additional indications are currently under investigation in ongoing clinical trials. Predictive biomarkers include microsatellite instability as well as tumor mutational burden. However, PD-L1 testing by immunohistochemistry (IHC) is already widely established as a biomarker in clinical routine for certain treatment decisions in non-small cell lung cancer, head and neck cancer and in urothelial carcinomas. More applications of that kind are expected to follow. Moreover, PD-L1 testing can provide clinicians with valuable information even if the test is not mandatory (i. e., complementary diagnostics). PD-L1 staining requires a highly specific staining over a broad dynamic range. Sensitive and specific primary antibodies and suitable staining protocols are prerequisite. Selection of appropriate patients’ materials, validation and contiguous quality assurance need to meet the highest standards. There are different scoring algorithms for PD-L1 stainings which are specific to tumor entities and certain clinical decisions. The tumor proportion score (TPS) is a PD-L1 measurement which is applied, for example, to lung cancer, head and neck cancer and melanomas. Within this approach, only membranous staining of tumor cells is regarded as a significant staining. In contrast, the combined positivity score (CPS) and inflammatory cell (IC) scoring include or are restricted to PD-L1 expression in certain inflammatory cells, respectively. CPS and IC scoring are standard measurements of PD-L1 in urothelial carcinoma.

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Change history

  • 29 May 2019

    Erratum zu:

    Pathologe 2018

    https://doi.org/10.1007/s00292-018-0507-x

    Bei der Publikation „Der prädiktive Wert der PD-L1-Diagnostik“ fehlt in der dritten Spalte von Tab. 5 am Ende der Formeln sowie in der Legende von Abb. 7 bei der Berechnung des CPS (50 + 250)/350 × 100 = 85 jeweils der Faktor …

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  1. Institut für Pathologie, Universitätsmedizin Göttingen, Robert-Koch-Straße 40, 37075, Göttingen, Deutschland

    H.-U. Schildhaus

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H.-U. Schildhaus gibt folgende potenziellen Interessenskonflikte an: Mitarbeiter der Targos Molecular Pathology GmbH, Kassel. Honorare: BMS, MSD, Roche, Pfizer, Novartis Oncology, Zytomed Systems. Lead/panel Institut für die QuIP GmbH, Assessor für NordiQC und UKNequas.

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Schildhaus, HU. Der prädiktive Wert der PD-L1-Diagnostik. Pathologe 39, 498–519 (2018). https://doi.org/10.1007/s00292-018-0507-x

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