HER-2-Diagnostik beim Mammakarzinom: Aktuelle Methoden und Zukunftsperspektiven

Zusammenfassung

Der transmembranöse HER-2-Rezeptor ist ein 185 kD schweres Protein, welches von dem Protoonkogen HER-2 auf dem langen Arm des Chromosoms 17 (17 q 12 - 21) kodiert wird. Bei etwa einem Drittel aller Mammakarzinome wird das HER-2-Protein überexprimiert. Eine wichtige Vorbedingung für den Einsatz der monoklonalen Antikörpertherapie mit Trastuzumab (Herceptin®) ist die Bestimmung des HER-2-Status. Verschiedene Testverfahren auf der Protein- (Immunhistochemie [IHC], Enzyme-linked Immunosorbent Assay [ELISA] und Western Blot) und auf der Genebene (Fluoreszenz-in-situ-Hybridisierung [FISH], chromogene In-situ-Hybridisierung [CISH], Polymerase-Ketten-Reaktion [PCR] und Southern Blot) stehen dafür zur Verfügung. Am häufigsten werden zurzeit die IHC und die FISH verwendet. Eine Kombination dieser beiden Verfahren wird zur Routinetestung empfohlen. Zunächst sollte die HER-2-Expression immunhistologisch untersucht werden. Fälle mit dem HercepTest-Score 2 + sollten dann mittels FISH nachuntersucht werden. Für die Zukunft stellt die CISH möglicherweise eine interessante Alternative zur FISH-Technik dar. Chromogene ersetzen bei dieser Methode Fluoreszenzfarbstoffe. CISH ermöglicht so die Verwendung von Lichtmikroskopen und Archivierung von Schnittpräparaten. Die quantitative ELISA-Bestimmung des abgespaltenen extrazellulären Anteils (ECD) des HER-2-Proteins im Patientenserum als Surrogatmarker für das Tumorvolumen stellt aus klinischer Sicht eine besonders interessante Zukunftsperspektive dar. Mit ihr könnte die Effektivität adjuvanter Therapien bzw. das Auftreten von Rezidiven frühzeitig festgestellt werden. Jedoch sollten zur endgültigen klinischen Validierung der CISH und des ELISA als Methoden der HER-2-Testung weitere prospektive Studien mit größeren Patientenzahlen folgen.

Abstract

The transmembrane HER-2 receptor is 185 kD of molecular weight and is encoded by the proto oncogene HER-2 on the long arm of chromosome 17 (17 q 12 - 21). Over-expression of HER-2 is found in about one third of all breast carcinomas. Determining the HER-2 status is a prerequisite for the use of the monoclonal antibody trastuzumab (Herceptin™) in the therapy of metastatic breast cancer. Various test assays for HER-2 either on the protein level (immunhistochemistry [IHC], enzyme-linked immunosorbent assay [ELISA], western blot) or on the gene level (fluorescence in situ hybridization [FISH], chromogenic in situ hybridization [CISH], polymerase chain reaction [PCR], and southern blot) are available. However, IHC and FISH are most often applied. For routine HER-2 testing a combination of both methods is recommended. IHC should be used for screening, followed by FISH only in those cases scored as 2 + by the HercepTest. In future, CISH may represent a useful alternative to FISH. In CISH fluorescent dyes are replaced by chromogenes, facilitating the use of light microscopes and the filing of slides. Quantitative analysis of the shed extracellular domain of HER-2 (HER-2 ECD) in the patients' serum by ELISA is helpful for clinical use. With HER-2 ECD as a surrogate marker of the tumor volume monitoring of adjuvant therapies and tumor recurrence would be feasible. However, more prospective studies with higher numbers of patients are required for validation of these new methods.

CISH - ELISA - FISH - HER-2 - Immunhistochemie - Mammakarzinom - PCR

Breast cancer - CISH - ELISA - FISH - HER-2 - immunohistochemistry - PCR

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