Comparison of central HER2 testing with quantitative total HER2 expression and HER2 homodimer measurements using a novel proximity-based assay.
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.
Huang
Weidong
W
Dept. of Clinical Research, Monogram Biosciences, South San Francisco, CA 94080, USA.
Reinholz
Monica
M
Weidler
Jodi
J
Yolanda
Lie
L
Paquet
Agnes
A
Whitcomb
Jeannette
J
Lingle
Wilma
W
Jenkins
Robert B
RB
Chen
Beiyun
B
Larson
Jeffrey S
JS
Tan
Yuping
Y
Sherwood
Thomas
T
Bates
Michael
M
Perez
Edith A
EA
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
D018719:Erb-b2 Receptor Tyrosine Kinases