Assessment of HER2 gene status in breast carcinomas with polysomy of chromosome 17.
BACKGROUND
The current study was performed to determine the impact of polysomy 17 on the interpretation of HER2 testing of invasive breast carcinomas using fluorescent in situ hybridization methods. Current American Society of Clinical Oncology/College of American Pathologists guidelines define HER2-positive tumors as those with >6 HER2 genes per nucleus or those with HER2/CEP17 (chromosome 17) ratio >2.2. These guidelines are potentially contradictory in tumors with polysomy of chromosome 17.


METHODS
Seventy-two breast carcinoma cases with reported polysomy of chromosome 17 (≥ 3 CEP17 signals on average) by fluorescent in situ hybridization were identified, and the corresponding HER2 immunohistochemistry was obtained. The HER2 status of the archived samples was reviewed, and the tumors were recategorized according to the 2007 American Society of Clinical Oncology/College of American Pathologists guidelines.


RESULTS
The average CEP17 copy number for the group was 4.5 (range, 3.0-10.4). Thirty-three (45.8%) cases had >6 copies of HER2 per nucleus. Twenty-one cases (29.2%) qualified as HER2 gene amplified using the HER2/CEP17 ratio (>2.2) guideline. All these cases had >6 HER2 signals, which represented 63.6% of all cases with >6 HER2 signals. HER2 protein expression showed significant positive correlations with both HER2 gene copy number and HER2/CEP17 ratio (P < .01, r(s) = 0.56 and 0.64, respectively).


CONCLUSIONS
Increased CEP17 signals detected in invasive breast carcinomas may lead to discordant interpretation of gene amplification in a significant proportion of the cases, depending on which criterion (ratio vs absolute number) is used for interpretation. However, increased gene dosage (>6 HER2 genes or HER2/CEP17 ratio >2.2), regardless of the evaluation method, is positively correlated with HER2 protein expression.
Vranic
Semir
S
Department of Pathology, Creighton University School of Medicine, Omaha, Nebraska 68131, USA.
Teruya
Bryan
B
Repertinger
Susan
S
Ulmer
Pamela
P
Hagenkord
Jill
J
Gatalica
Zoran
Z
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000782:Aneuploidy; D001943:Breast Neoplasms / Q000235:genetics*; D002886:Chromosomes, Human, Pair 17; D056915:DNA Copy Number Variations; D005260:Female; D018734:Genes, erbB-2; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism
D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human