title: Comparison of central HER2 testing with quantitative total HER2 expression and HER2 homodimer measurements using a novel proximity-based assay.
abstract: The accuracy and reliability of immunohistochemical analysis and in situ hybridization for the assessment of HER2 status remains a subject of debate. We developed a novel assay (HERmark Breast Cancer Assay, Monogram Biosciences, South San Francisco, CA) that provides precise quantification of total HER2 protein expression (H2T) and HER2 homodimers (H2D) in formalin-fixed, paraffin-embedded tissue specimens. H2T and H2D results of 237 breast cancers were compared with those of immunohistochemical studies and fluorescence in situ hybridization (FISH) centrally performed at the Mayo Clinic, Rochester, MN. H2T described a continuum across a wide dynamic range ( approximately 2.5 log). Excluding the equivocal cases, HERmark showed 98% concordance with immunohistochemical studies for positive and negative assay values. For the 94 immunohistochemically equivocal cases, 67% and 39% concordance values were observed between HERmark and FISH for positive and negative assay values, respectively. Polysomy 17 in the absence of HER2 gene amplification did not result in HER2 overexpression as evaluated quantitatively using the HERmark assay.
authors.affiliation: Dept. of Clinical Research, Monogram Biosciences, South San Francisco, CA 94080, USA.
authors.forename: Weidong
authors.initials: W
authors.lastname: Huang
authors.forename: Monica
authors.initials: M
authors.lastname: Reinholz
authors.forename: Jodi
authors.initials: J
authors.lastname: Weidler
authors.forename: Lie
authors.initials: L
authors.lastname: Yolanda
authors.forename: Agnes
authors.initials: A
authors.lastname: Paquet
authors.forename: Jeannette
authors.initials: J
authors.lastname: Whitcomb
authors.forename: Wilma
authors.initials: W
authors.lastname: Lingle
authors.forename: Robert B
authors.initials: RB
authors.lastname: Jenkins
authors.forename: Beiyun
authors.initials: B
authors.lastname: Chen
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Larson
authors.forename: Yuping
authors.initials: Y
authors.lastname: Tan
authors.forename: Thomas
authors.initials: T
authors.lastname: Sherwood
authors.forename: Michael
authors.initials: M
authors.lastname: Bates
authors.forename: Edith A
authors.initials: EA
authors.lastname: Perez
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005455:Fluorescent Antibody Technique / Q000379:methods*; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis* / Q000096:biosynthesis / Q000235:genetics; D015203:Reproducibility of Results
chemical_list: D018719:Erb-b2 Receptor Tyrosine Kinases