Breast cancers with a HER2/CEP17 ratio of 2.0 or greater and an average HER2 copy number of less than 4.0 per cell: frequency, immunohistochemical correlation, and clinicopathological features

The 2013 American Society of Clinical Oncology and College of American Pathologists (ASCO/CAP) guidelines classified breast cancers with a fluorescence in situ hybridization dual-probe HER2/CEP17 ratio of 2 or greater as “amplified,” inclusive of cases with a HER2 copy number less than 4. The 2018 A...

Full description

Saved in:
Bibliographic Details
Published in:Human pathology Vol. 83; pp. 7 - 13
Main Authors: Zare, Somaye Y., Lin, Leo, Alghamdi, Abrar G., Daehne, Svenja, Roma, Andres A., Hasteh, Farnaz, Dell'Aquila, Marie, Fadare, Oluwole
Format: Journal Article
Language:English
Published: United States Elsevier Inc 01.01.2019
Elsevier Limited
Subjects:
Adult
Aged
Aged, 80 and over
Biomarkers, Tumor - analysis
Biomarkers, Tumor - genetics
Breast cancer
Breast Neoplasms - classification
Breast Neoplasms - genetics
Breast Neoplasms - pathology
Centromere enumeration probe for chromosome 17
Chromosome 17 monosomy
Chromosomes
Chromosomes, Human, Pair 17 - genetics
Female
Fluorescence in situ hybridization
Gene Dosage
Gene Expression Profiling - methods
Genes, erbB-2
Human epidermal growth factor receptor 2
Humans
Hybridization
Immunohistochemistry
Lymphatic system
Middle Aged
Receptor, ErbB-2 - analysis
Receptor, ErbB-2 - genetics
Tumors
Young Adult
Chromosome 17 monosomy
Breast cancer
Human epidermal growth factor receptor 2
Centromere enumeration probe for chromosome 17
Fluorescence in situ hybridization
ISSN:0046-8177, 1532-8392, 1532-8392
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The 2013 American Society of Clinical Oncology and College of American Pathologists (ASCO/CAP) guidelines classified breast cancers with a fluorescence in situ hybridization dual-probe HER2/CEP17 ratio of 2 or greater as “amplified,” inclusive of cases with a HER2 copy number less than 4. The 2018 ASCO/CAP update assigns HER2/neu status for the latter group in a fashion that is highly dependent on the associated immunohistochemical findings. Herein, the authors define the frequency, immunohistochemical correlates, and other clinicopathological features of breast cancers with HER2/CEP17 ratio of 2 or greater and HER2/neu copy number less than 4 (group A), based on an analysis of an institutional cohort assessed for HER2/neu status by both florescence in situ hybridization and immunohistochemistry and scored using 2013 ASCO/CAP criteria. Group A cases were compared with a group B of HER2/neu-amplified breast cancers with a HER2/neu copy number of 4 or greater regarding a variety of clinicopathological features. One hundred sixty-nine (14%) of 1201 cases were HER2/neu amplified, 18 (10.7%) in group A and 151 (89.3%) in group B. By immunohistochemistry, 61.1% of group A cases were HER2/neu negative, 7 (38.9%) were equivocal, and none were positive. In contrast, 66.9% of group B cases were HER2 positive (3+). We could not demonstrate statistically significant differences between the 2 groups regarding standard clinicopathological variables. In summary, our group A cases account for 1.5% of breast cancers, and 10.7% of all HER2/neu-amplified cancers classified as such based on 2013 ASCO/CAP criteria. They are predominantly HER2/neu negative by immunohistochemistry, which suggests that they are biologically different from classically HER2/neu-amplified cases and which validates the 2018 ASCO/CAP guideline against automatically classifying such cases as HER2/neu amplified. •Breast cancers with HER2/CEP17 ratio of 2 or greater and HER2 copy number less than 4 account for 1.5% of breast cancers.•Sixty-one percent of breast cancers with HER2/CEP17 ratio of 2 or greater and HER2 copy number less than 4 are HER2 negative by IHC.•None of the breast cancers with HER2/CEP17 ratio of 2 or greater and HER2 copy number less than 4 were HER2 positive by IHC.•The findings are supportive of the 2018 ASCO/CAP guideline classifying these cases as HER2 negative.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 14
content type line 23
ISSN:0046-8177
1532-8392
1532-8392
DOI:10.1016/j.humpath.2018.08.005