title: Relationship between HER2 status and proliferation rate in breast cancer assessed by immunohistochemistry, fluorescence in situ hybridisation and standardised AgNOR analysis.
abstract: Lack of standardisation and inaccuracy in HER2 test results may adversely influence patient evaluation and therapy selection. In the present study we applied immunohistochemistry (IHC) using the A0485 and CB11 antibodies and fluorescence in situ hybridisation (FISH) for detection of HER2 in 74 routinely processed breast carcinoma specimens. The rapidity of cellular proliferation was assessed by standardised AgNOR analysis and compared with HER2 status. Protein over-expression was found in 30/74 cases by A0485 and in 20/74 by CB11 antibodies, while amplification was detected in 22/74 carcinomas by FISH. Twenty-seven of 74 tumours were high-level AgNOR expressors (mean AgNOR area >3.369 microm2), 19 of which revealed amplification. The highest concordance between results was achieved by FISH and CB11-IHC (97%), the concordance between FISH and A0485-IHC was 89 and 84% between FISH and AgNOR quantity, respectively. The overall concordance between A0485 and CB11-IHC was 85% with 10 incongruent cases, all scored 2+ by A0485 and 0/1+ by CB11. Eight of the discordant tumours were non-amplified by FISH and 7 were low AgNOR-expressors. Our results indicate that using CB11 antibody, a nearly complete agreement can be achieved between HER2 IHC and FISH in diagnostic paraffin material. Moreover, in 2+ positive IHC cases, the AgNOR analysis may represent an additional tool to select patients as candidates for Herceptin therapy due to the strong negative predictor value.
authors.affiliation: Institute of Pathology, University of Muenster, D-48149 Muenster, Germany. bankfal@uni-muenster.de
authors.forename: Agnes
authors.initials: A
authors.lastname: Bánkfalvi
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Giuffrè
authors.forename: Dietmar
authors.initials: D
authors.lastname: Ofner
authors.forename: Raihanatou
authors.initials: R
authors.lastname: Diallo
authors.forename: Christopher
authors.initials: C
authors.lastname: Poremba
authors.forename: Igor B
authors.initials: IB
authors.lastname: Buchwalow
authors.forename: Valeria
authors.initials: V
authors.lastname: Barresi
authors.forename: Werner
authors.initials: W
authors.lastname: Böcker
authors.forename: Giovanni
authors.initials: G
authors.lastname: Tuccari
mesh_terms: D001943:Breast Neoplasms / Q000473:pathology*; D002455:Cell Division; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods*; D017404:In Situ Hybridization, Fluorescence / Q000379:methods*; D009697:Nucleolus Organizer Region / Q000473:pathology; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis*; D012834:Silver / Q000494:pharmacology; D013194:Staining and Labeling
chemical_list: D018719:Erb-b2 Receptor Tyrosine Kinases; D012834:Silver