title: The relation between percentage of immunostained cells and amplification status in breast cancers with equivocal result for Her2 immunohistochemistry.
abstract: We analyzed Her2 amplification in breast cancers with equivocal IHC staining to investigate the significance of percentage of Her2 immunostained tumor cells. We especially included the breast cancers with complete/incomplete membrane staining at moderate intensity in less than 10% of the invasive tumor cells. Of 1804 breast cases, 180 had moderate complete/incomplete membrane Her2 immunostaining. According to 2013 ASCO/CAP guideline, 124 were in IHC score 2+ and 56 in 1+ category. The percentage of Her2 immunostained invasive tumor cells were determined by visual estimation at the time of diagnosis and categorized into three groups; <10%, 10-50%, and >50% for this review. FISH was performed by dual DNA probe and data of Her2/cep17 ratio, Her2/cell and Cep17/cell were recorded applying 2013 ASCO/CAP criteria. There were 22 cases (12.2%) in >50% group, 102 (56.7%) in 10-50% group, and 56 (31.1%) in <10% group. Overall Her2 amplification was 25.5%. Her2 was amplified in 12 (54.5%) cases in >50% group; 26 (25.4%) in 10-50% and 8 (14.3%) in <10%. Her2 amplification was more frequent in cancers with >50% moderately immunostained cells in IHC equivocal group. However, most of Her2 IHC equivocal breast cancers contain moderate amount (10-50%) of immunostained cells. Relatively small but non-neglectable number (14%) of cases in <10% group was Her2 amplified by FISH which approaches to overall incidence of Her2 overexpression (15-20%) in all breast cancer. Breast cancers with moderate complete/incomplete membrane Her2 IHC staining in <10% of invasive tumor cells should be regarded as equivocal and reflex FISH should be performed in these cases.
authors.affiliation: Department of Pathology, GATA and TUBITAK, Ankara, Turkey; Department of Pathology and Laboratory Medicine, University of Pennsylvania Medical Center, Philadelphia, PA, USA. Electronic address: onguruo@yahoo.com.
authors.forename: Onder
authors.initials: O
authors.lastname: Onguru
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Pennsylvania Medical Center, Philadelphia, PA, USA.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Zhang
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D016208:Databases, Factual; D005260:Female; D005784:Gene Amplification; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*
chemical_list: D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human
keywords: Breast cancer; Equivocal; FISH; Her2; Immunohistochemistry