title: Genetic alterations and protein expression of HER2 and chromosome 17 polysomy in breast cancer.
abstract: HER2/neu alteration detection in breast cancer is important for decision making of the HER2-targeted therapy. We retrospectively analyzed the HER2/neu status by fluorescence in situ hybridization and HER2 protein expression by immunohistochemistry in a cohort of 481 patients with invasive breast cancer. Fluorescence in situ hybridization showed that 57.4% of cases exhibited HER2 amplification but 41.4% did not, and 1.2% exhibited an equivocal status. Immunohistochemistry showed that 10.4%, 16.8%, 38.3%, and 34.5% of cases had scores of 0, 1+, 2+, and 3+, respectively. The HER2 status showed a moderate agreement with HER2 expression with a score of 0, 1+, and 3+ (κ = 0.576, P < .05), and the concordance rate was 90%, 61.7%, and 83.1%, respectively. The HER2 amplification occurred more likely in cases with higher immunohistochemistry scores (P < .001), and polysomy 17 was observed in 28.3% of cases, but more frequently in the HER2 amplification subgroup (33.3%) than in the HER2 nonamplification subgroup (20.1%) (P < .05). There was no significant correlation between the frequency of polysomy 17 and immunohistochemistry scores (P > .05). In the immunohistochemistry 2+ group, 56.5% cases showed HER2/neu amplification, and polysomy 17 occurred more likely in the HER2 amplification subgroup (34.6%) than in the HER2 nonamplification group (13.0%) (P < .001). We concluded that the HER2 status was correlated with HER2 protein expression levels, and it is necessary to determine the HER2 status for cases with immunohistochemistry 2+. The frequency of polysomy 17 was correlated with the HER2 copy number and partially contributed to HER2/neu amplification but not HER2 protein expression.
authors.affiliation: Department of Pathology, Cancer Hospital and Department of Oncology, Shanghai Medical School, Fudan University, Shanghai 200032, China.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Zhu
authors.forename: Yongming
authors.initials: Y
authors.lastname: Lu
authors.forename: Hongfen
authors.initials: H
authors.lastname: Lu
authors.forename: Wentao
authors.initials: W
authors.lastname: Yang
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Tu
authors.forename: Xu
authors.initials: X
authors.lastname: Cai
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Zhou
mesh_terms: D000782:Aneuploidy; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics*; D005260:Female; D005784:Gene Amplification; D018628:Gene Dosage; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D012189:Retrospective Studies
chemical_list: D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human