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HER2-Rezeptoren des Mamma - Karzinoms |
| allgemeines | Viele Mammakarzinome enthalten auf der Zelloberfläche Rezeptoren für den Epithelial - Growth - Factor (EGF).
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| Wirkung | Eine Stimulation der EGF-Rezeptoren (EGFR) bewirkt eine rasche Proliferation.
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| Trastzumab | Diese Stimulation lässt sich durch eine Therapie mit Trastzumab (Herzeptin) unterdrücken. Voraussetzung für diese Therapie, ist der Nachweis von Her-2/neu. Folgende Kriterien werden in diversen Leitlinien empfohlen:
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| Score |
| IHC-Score |
Her - 2 - Status |
immunhistochemische Membranreaktion |
| +++ |
positiv |
gleichmäßig
intensiv
zirkulär
>30% der Tumorzellen |
| ++ |
zweifelhaft |
ungleichmäßig oder schwach
zirkulär, >10% der Tumorzellen |
| 0 oder + |
positiv |
keine oder schwach, inkomplett |
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FISH-Analyse |
Sondenkit ZytoLight Dual Color Probe (ZytoVision) |
Es werden 30 Tumorzellkerne ausgezählt. |
Quotient A: Gen / Zentromersignal. |
Quotient B: Gensignale / gezählte Kerne |
| FISH | bei zweifelhaftem IHC-Score: FISH (Fluorescence In Situ Hybridization) /
CISH (Silver in situ hybridization) - Test
| Status |
Her-2/
CEP17 |
Her - 2 - Genkopien |
| positiv |
> 2,2 |
> 6 |
| zweifelhaft |
1,8 - 2,2 |
4 - 6 |
| negativ |
< 1,8 |
<4 |
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Ventana |
Die Firma Ventana hat einen monoklonalen Mausantikörper gegen Her2neu entwickelt: Ventana Pathway Her-2 (4B5). Die Anwendung erfolgt in einem automatisierten immunhistochemischen Färbeautomaten.
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ASCO |
Empfehlungen des American Society of Clinical Oncology (ASCO) und des College of American Pathologists (CAP)(1) |
Quellen |
1.) Wolff AC, et al.:
Recommendations for human epidermal growth factor receptor 2 testing in breast cancer: ASCO / CAP Clinical Practice Guideline Update.
J Clin Oncol 31(2013): 3997 – 4013
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Am J Surg Pathol. 2010 Jun;34(6):767-76. doi: 10.1097/PAS.0b013e3181d96231.
Silver in situ hybridization (SISH) for determination of HER2 gene status in breast carcinoma: comparison with FISH and assessment of interobserver reproducibility.
Papouchado BG1, Myles J, Lloyd RV, Stoler M, Oliveira AM, Downs-Kelly E, Morey A, Bilous M, Nagle R, Prescott N, Wang L, Dragovich L, McElhinny A, Garcia CF, Ranger-Moore J, Free H, Powell W, Loftus M, Pettay J, Gaire F, Roberts C, Dietel M, Roche P, Grogan T, Tubbs R.
Author information
Abstract
The importance of HER2 status in breast cancer management has focused attention on the ability of clinical assays to correctly assign HER2 amplification status.
There is no consensus as to the best method for assessing HER2 status.
Disadvantages of fluorescence in situ hybridization (FISH) testing include longer time required for staining and scoring slides,
requirements for specialized training and fluorescence microscopy, and loss of the signal due to quenching of the fluorescent dye.
Silver-enhanced in situ hybridization (SISH) is a rapid fully automated assay providing permanently stained slides that are interpreted
by conventional bright field microscopy which enables pathologists to evaluate slides within the context of tissue morphology.
This study evaluates the concordance between SISH and FISH assays in determining the status of HER2 gene amplification in a cohort of
298 primary invasive breast carcinomas. Furthermore, we assessed in detail the variables contributing to interobserver interpretive reproducibility of
HER2 SISH among 10 pathologists. HER2 was quantified using the ratio of HER2 to CHR17 signals using the conventional historical interpretation scale
and also by the American Society of Clinical Oncology/College of American Pathologists reporting scheme. For SISH status determined by consensus
among 10 pathologists, overall concordance between SISH and FISH was identified in 288 of 298 cases (96.6%) using the conventional Food and Drug
Administration approved criteria. Overall agreement was observed in 282 of 285 cases (98.9%) using the
American Society of Clinical Oncology/College of American Pathologists result reporting scheme (with equivocal cases removed).
In conclusion, SISH represents a novel approach for the determination of HER2 status in breast cancer.
The overall concordance between SISH and FISH is excellent, and the interpretation of SISH results by pathologists is most reproducible using the HER2/CHR17 ratio.
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