title: Distribution pattern of the Ki67 labelling index in breast cancer and its implications for choosing cut-off values.
abstract: The Ki67 labelling index (LI - proportion of staining cells) is widely used to reflect proliferation in breast carcinomas. Several cut-off values have been suggested to distinguish between tumours with low and high proliferative activity. The aim of the current study was to evaluate the distribution of Ki67 LIs in breast carcinomas diagnosed at different institutions by different pathologists using the method reflecting their daily practice. Pathologists using Ki67 were asked to provide data (including the LI, type of the specimen, receptor status, grade) on 100 consecutively stained cases, as well as details of their evaluation. A full dataset of 1709 carcinomas was collected from 19 departments. The median Ki67 LI was 17% for all tumours and 14% for oestrogen receptor-positive and HER2-negative carcinomas. Tumours with higher mitotic counts were associated with higher Ki67 LIs. Ki67 LIs tended to cluster around values ending with 5 or 0 both in cases where the values were obtained by counting the proportion of stained tumour cell nuclei and those where the values were obtained by estimation. On the basis of the distribution pattern described, some currently used Ki67 LI cut off values are not realistic, and it is proposed to select more realistic values ending with 0 or 5.
authors.affiliation: Bács-Kiskun County Teaching Hospital, Kecskemét, Hungary; Department of Pathology, University of Szeged, Hungary. Electronic address: cserni@freemail.hu.
authors.forename: Gábor
authors.initials: G
authors.lastname: Cserni
authors.affiliation: Department of Pathology, University of Szeged, Hungary.
authors.forename: András
authors.initials: A
authors.lastname: Vörös
authors.affiliation: Pathology Centre, Riga East Clinical University Hospital, Riga, Latvia.
authors.forename: Inta
authors.initials: I
authors.lastname: Liepniece-Karele
authors.affiliation: Section of Pathological Anatomy, Department of Surgery and Translational Medicine, University of Florence, AOU Careggi, Largo GA Brambilla 3, 50134 Florence, Italy.
authors.forename: Simonetta
authors.initials: S
authors.lastname: Bianchi
authors.affiliation: Section of Pathological Anatomy, Department of Surgery and Translational Medicine, University of Florence, AOU Careggi, Largo GA Brambilla 3, 50134 Florence, Italy.
authors.forename: Vania
authors.initials: V
authors.lastname: Vezzosi
authors.affiliation: Department of Pathology, Skåne University Hospital, Lund, Sweden.
authors.forename: Dorthe
authors.initials: D
authors.lastname: Grabau
authors.affiliation: Department of Medical Sciences, University of Turin, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Sapino
authors.affiliation: Department of Medical Sciences, University of Turin, Italy.
authors.forename: Isabella
authors.initials: I
authors.lastname: Castellano
authors.affiliation: Medical University of Graz, Institute of Pathology, Auenbruggerplatz 25, A-8036 Graz, Austria.
authors.forename: Peter
authors.initials: P
authors.lastname: Regitnig
authors.affiliation: Department of Biomedical and Neuromotor Sciences, University of Bologna, Anatomic Pathology at Bellaria Hospital, Via Altura, 3, 40139 Bologna, Italy.
authors.forename: Maria Pia
authors.initials: MP
authors.lastname: Foschini
authors.affiliation: Department of Pathology, Medical School, University of Patras, Rion, Patras, Greece.
authors.forename: Vassiliki
authors.initials: V
authors.lastname: Zolota
authors.affiliation: Institute of Surgical Pathology, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Varga
authors.affiliation: Lab Histopatologia, Av Bissaya Barreto, Apartado 2005, 3001-651 Coimbra, Portugal.
authors.forename: Paulo
authors.initials: P
authors.lastname: Figueiredo
authors.affiliation: Department of Pathology, Dietrich Bonhoeffer Medical Centre, Allendestraße 30, D-17036 Neubrandenburg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Decker
authors.affiliation: Department of Pathology, Dietrich Bonhoeffer Medical Centre, Allendestraße 30, D-17036 Neubrandenburg, Germany.
authors.forename: Cornelia
authors.initials: C
authors.lastname: Focke
authors.affiliation: 2nd Department of Pathology, Semmelweis University Budapest, Üllői út 93, H-1091 Budapest, Hungary.
authors.forename: Janina
authors.initials: J
authors.lastname: Kulka
authors.affiliation: Marmara University School of Medicine, Department of Pathology, Istanbul, Turkey.
authors.forename: Handan
authors.initials: H
authors.lastname: Kaya
authors.affiliation: Institute of Pathology, Danube Hospital, Langobardenstrasse 122, A-1220 Vienna, Austria.
authors.forename: Angelika
authors.initials: A
authors.lastname: Reiner-Concin
authors.affiliation: Department of Pathology, Centro Hospitalar de S. João and Instituto de Patologia e Imunologia Molecular da Universidade do Porto (IPATIMUP), Portugal.
authors.forename: Isabel
authors.initials: I
authors.lastname: Amendoeira
authors.affiliation: Discipline of Pathology, NUI Galway, Galway, Ireland.
authors.forename: Grace
authors.initials: G
authors.lastname: Callagy
authors.affiliation: Discipline of Pathology, NUI Galway, Galway, Ireland.
authors.forename: Emer
authors.initials: E
authors.lastname: Caffrey
authors.affiliation: Department of Pathology, Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands; Department of Molecular Pathology, Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.
authors.forename: Jelle
authors.initials: J
authors.lastname: Wesseling
authors.affiliation: Department of Pathology, University College Hospital, London, United Kingdom.
authors.forename: Clive
authors.initials: C
authors.lastname: Wells
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism; D001943:Breast Neoplasms / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology; D002467:Cell Nucleus / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods / Q000592:standards; D019394:Ki-67 Antigen / Q000378:metabolism*; D008940:Mitotic Index; D060787:Neoplasm Grading; D011237:Predictive Value of Tests; D011379:Prognosis; D012016:Reference Values; D013194:Staining and Labeling / Q000379:methods
chemical_list: D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen
keywords: Breast cancer; Ki67; Proliferation