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Eur J Cancer. 2017 Oct;84:219-227. doi: 10.1016/j.ejca.2017.07.041. Epub 2017 Aug 19.

Interlaboratory variability of Ki67 staining in breast cancer.

Author information

1
Department of Pathology, Dietrich Bonhoeffer Medical Centre, Allendestrasse 30, 17033 Neubrandenburg, Germany; Department of Pathology, University Medical Centre Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands. Electronic address: cornelia.focke@web.de.
2
Institute of Pathology Paderborn/Höxter, Breast Center Paderborn, Husener Str. 46 a, 33098 Paderborn, Germany.
3
Department of Pathology, University Medical Centre Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands.
4
Department of Pathology, Dietrich Bonhoeffer Medical Centre, Allendestrasse 30, 17033 Neubrandenburg, Germany.
5
Institute of Bioinformatics, University of Münster, Niels-Stensen-Straße 14, 48149 Münster, Germany.
6
Joint Practice for Pathology, Greifswald, Germany.
7
Joint Practice for Pathology, Bonn, Germany.
8
Department of Pathology, St. Agnes Hospital, Bocholt, Germany.
9
Department of Pathology, Carl Gustav Carus University of Dresden, Germany.
10
Joint Practice for Pathology, Chemnitz, Germany.
11
Georg Schmorl Institute of Pathology, Dresden-Friedrichstadt, Germany.
12
Medical Care Center for Pathology and Cytology, Köln, Germany.
13
Department of Pathology, Medical Center Dessau, Germany.
14
Department of Pathology, Medical Center Herford, Germany.
15
Department of Pathology, Medical Center Dortmund, Germany.
16
Joint Practice for Pathology, Eisenhüttenstadt, Germany.
17
Practice for Pathology, Moers, Germany.
18
Joint Practice for Pathology, Leipzig, Germany.
19
Joint Practice for Pathology, Osnabrück, Germany.
20
Joint Practice for Pathology, Bielefeld, Germany.
21
Department of Pathology, Evangelisches Waldkrankenhaus, Berlin, Germany.
22
Joint Practice for Pathology, Schwerin, Germany.
23
Joint Practice for Pathology and Cytology, Stendal, Germany.
24
Joint Practice for Pathology, Dresden, Germany.
25
Practice for Pathology, Berlin, Germany.
26
Institute of Pathology, Thüringen-Hospital Georgius Agricola, Saalfeld, Germany.
27
MVZ Hanse Histologikum, Hamburg, Germany.
28
Bács-Kiskun County Teaching Hospital, Department of Pathology, Kecskemét, Hungary.
29
Immunohistochemical Lab Habedank, Berlin, Germany.
30
Department of Pathology, LKH West, Graz, Austria.
31
Department of Pathology, University of Graz, Austria.
32
Department of Pathology, Donauspital Vienna, Austria.
33
Institute of Pathology Nordhessen, Kassel, Germany.
34
Department of Pathology, University of Zürich, Switzerland.
35
Institute of Pathology, Aurich, Germany.

Abstract

BACKGROUND:

Postanalytic issues of Ki67 assessment in breast cancers like counting method standardisation and interrater bias have been subject of various studies, but little is known about analytic variability of Ki67 staining between pathology labs. Our aim was to study interlaboratory variability of Ki67 staining in breast cancer using tissue microarrays (TMAs) and central assessment to minimise preanalytic and postanalytic influences.

METHODS:

Thirty European pathology labs stained serial slides of a TMA set of breast cancer tissues with Ki67 according to their routine in-house protocol. The Ki67-labelling index (Ki67-LI) of 70 matched samples was centrally assessed by one observer who counted all cancer cells per sample. We then tested for differences between the labs in Ki67-LI medians by analysing variance on ranks and in proportions of tumours classified as luminal A after dichotomising oestrogen receptor-positive cancers into cancers showing low (<14%, luminal A) and high (≥14%, luminal B HER2 negative) Ki67-LI using Cochran's Q.

RESULTS:

Substantial differences between the 30 labs were indicated for median Ki67-LI (0.65%-33.0%, p < 0.0001) and proportion of cancers classified as luminal A (17%-57%, p < 0.0001). The differences remained significant when labs using the same antibody (MIB-1, SP6, or 30-9) were analysed separately or labs without prior participation in external quality assurance programs were excluded (p < 0.0001, respectively).

CONCLUSION:

Substantial variability in Ki67 staining of breast cancer tissue was found between 30 routine pathology labs. Clinical use of the Ki67-LI for therapeutic decisions should be considered only fully aware of lab-specific reference values.

KEYWORDS:

Breast cancer; Immunohistochemistry; Ki67; Proliferation; St Gallen consensus; Subtyping; Variability

PMID:
28829990
DOI:
10.1016/j.ejca.2017.07.041
[Indexed for MEDLINE]

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