title: An international study comparing conventional versus mRNA level testing (TargetPrint) for ER, PR, and HER2 status of breast cancer.
abstract: To compare results from messenger RNA (mRNA)-based TargetPrint testing with those from immunohistochemistry (IHC) and in situ hybridization (ISH) conducted according to local standard procedures at hospitals worldwide. Tumor samples were prospectively obtained from 806 patients at 22 hospitals. The mRNA level of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) was assessed by TargetPrint quantitative gene expression readouts. IHC/ISH assessments were performed according to local standards at the participating hospitals. TargetPrint readout showed a high concordance with IHC/ISH of 95 % (kappa 0.81) for ER, 81 % (kappa 0.56) for PR, and 94 % (kappa 0.76) for HER2. The positive/negative agreement between TargetPrint and IHC for ER, PR, and HER2 was 96 %/87 %, 84 %/74 %, and 74 %/98 %, respectively. The concordance rate in IHC/ISH results between hospitals varied: 88-100 % for ER (kappa 0.50-1.00); 50-100 % for PR (kappa 0.20-1.00); and 90-100 % for HER2 (kappa 0.59-1.00). mRNA readout of ER, PR, and HER2 status by TargetPrint was largely comparable to local IHC/ISH analysis. However, there was substantial discordance in IHC/ISH results between different hospitals. When results are discordant, the use of TargetPrint would improve the reliability of hormone receptor and HER2 results by prompting retesting in a reference laboratory.
authors.affiliation: Department of Pathology, The Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands. j.wesseling@nki.nl.
authors.forename: Jelle
authors.initials: J
authors.lastname: Wesseling
authors.affiliation: Breast Surgery, Istituto Clinico Humanitas IRCCS, Rozzano, Milan, Italy.
authors.forename: Corrado
authors.initials: C
authors.lastname: Tinterri
authors.affiliation: Department of Medical Sciences, Università di Torino, Torino, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Sapino
authors.affiliation: Anatomic Pathology Unit, Università di Trieste, Trieste, Italy.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Zanconati
authors.affiliation: Department of Surgery, Medisch Spectrum Twente, Enschede and the Saxenburgh Group, Hardenberg, The Netherlands.
authors.forename: Martijn
authors.initials: M
authors.lastname: Lutke-Holzik
authors.affiliation: Department of Medicine, Todd Cancer Institute, Long Beach Memorial Medical Center, Long Beach, CA, USA.
authors.forename: Bichlien
authors.initials: B
authors.lastname: Nguyen
authors.affiliation: Memorial Care Breast Center, Saddleback Memorial Medical Center, Laguna Hills, CA, USA.
authors.forename: Kenneth B
authors.initials: KB
authors.lastname: Deck
authors.affiliation: Section of Anatomic Pathology, Department of Experimental and Diagnostic Medicine, Università di Ferrara, Ferrara, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Querzoli
authors.affiliation: Division of Pathology, Centro di Riferimento Oncologico, National Cancer Institute, Aviano, Italy.
authors.forename: Tiziana
authors.initials: T
authors.lastname: Perin
authors.affiliation: Department of Pathological Anatomy, Università degli Studi di Bari, Bari, Italy.
authors.forename: Carmela
authors.initials: C
authors.lastname: Giardina
authors.affiliation: Institute of Pathology, Klinikum Bamberg, Bamberg, Germany.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Seitz
authors.affiliation: Department of Pathology, Institut Curie, Hôpital René-Huguenin, Saint-Cloud, France.
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Guinebretière
authors.affiliation: Comprehensive Breast Care of San Diego and Sharp Memorial Hospital, San Diego, CA, USA.
authors.forename: Julie
authors.initials: J
authors.lastname: Barone
authors.affiliation: Agendia, Amsterdam, The Netherlands.
authors.forename: Laura
authors.initials: L
authors.lastname: Dekker
authors.affiliation: Agendia, Amsterdam, The Netherlands.
authors.forename: Femke
authors.initials: F
authors.lastname: de Snoo
authors.affiliation: Agendia, Amsterdam, The Netherlands.
authors.forename: Lisette
authors.initials: L
authors.lastname: Stork-Sloots
authors.affiliation: Agendia, Amsterdam, The Netherlands.
authors.forename: Paul
authors.initials: P
authors.lastname: Roepman
authors.affiliation: Department of Medicine, Hamamatsu Oncology Center, Shizuoka, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Watanabe
authors.affiliation: Gynecology Oncology Unit, Centre Hospitalier Chrétien, Liège, Belgium.
authors.forename: Pino
authors.initials: P
authors.lastname: Cusumano
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008875:Middle Aged; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000378:metabolism*; D011980:Receptors, Progesterone / Q000378:metabolism; D015203:Reproducibility of Results; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C508053:ERBB2 protein, human
keywords: Breast cancer; ER; Her-2; IHC/Fish; PgR; mRNA