Amplification of Chromosome 17 Centromere (CEP17) in Breast Cancer Patients with a Result of HER2 2± by Immunohistochemistry

Abstract

Background: Amplification of the centromeric region of chromosome 17 (CEP17) as measured by In Situ Hybridization (ISH) of the CEP17 probe is used clinically as part of the ISH assay for HER2 status determination in breast cancer. The value of amplification of CEP17 beyond its use in the HER2 ISH test has not been fully explored.Methods: A retrospective review of patients with breast cancer that had a dual probe HER2/CEP17 FISH test during an eight-year period was performed. Data on demographic and cancer-specific characteristics of the included patients were extracted. The group of patients with an amplified CEP17 defined as mean copy number of ≥3 per nucleus was compared with the group without amplification.Results: Two hundred and twelve patients were eligible and included in the analysis. Amplification of CEP17 was observed in 39 patients (18.4%). All patients in the amplified group had a concomitant amplification of HER2 (mean copy number ≥3 per nucleus). In the CEP17 non-amplified group 82 of 172 patients (47.7%) had an amplified HER2 status. More patients in the amplified group had a clinical HER2+ status according to the 3-protein classifier (30.8% versus 12.3% in the non-amplified group) and fewer patients in the amplified group had a clinical ER+/HER2- status (66.7% versus 81.3% in the non-amplified group, x2 p = .01). Other significant differences between the amplified and CEP17 non-amplified groups were observed in their lymph node (LN) status (56.4% of patients in the amplified group versus 38.8% in the non-amplified group were lymph node positive, p = .04) and in the nuclear heterogeneity component of grade (91.2% of patients in the amplified group were nuclear grade 3 versus 67.1% in the non-amplified group, p = .005). There were no statistically significant differences between the groups in overall stage, grade, menopause status or histology. Recurrence Free Survival (RFS) was shorter in stage I to III patients with an amplified CEP17 compared with the non-amplified group.Conclusion: Patients with amplification of CEP17 had a co-amplified HER2 and were more commonly HER2+, LN positive and grade 3 in the nuclear component of grade.