Co-amplification of the HER2 gene and chromosome 17 centromere: a potential diagnostic pitfall in HER2 testing in breast cancer

Breast Cancer Res Treat. 2012 Apr;132(3):925-35. doi: 10.1007/s10549-011-1642-8. Epub 2011 Jun 23.


Co-amplification of the centromere on chromosome 17 (CEP17) and HER2 can occur in breast cancer. Such aberrant patterns (clusters) on CEP17 can be misleading to calculate the HER2/CEP17 ratio, and thus underreporting of HER2 amplification. We identified 14 breast cancers retrospectively with HER2/CEP17 co-amplification and performed FISH (fluorescence in situ hybridization) with additional chromosome 17 probes (17p11.1-q11.1, 17p11.2-p12, TP53 on 17p13.1, RARA on 17q21.1-3 and TOP2 on 17q21.3-22) to characterize the spanning of the amplicon in these cases. Furthermore, the HER2 status was analyzed by means of HER2 silver in situ hybridization (SISH) and immunohistochemistry (IHC). The co-amplification of HER2/CEP17 was compared between the three institutions. TP53 was eusomic in all cases, 17p11.2-p12 in 79% (11/14), whereas 17p11.1-q11.1 showed chromosomal gain in all cases. RARA was amplified in 10/14 cases (71%) and TOP2 in 3/14 cases (21%). HER2 was amplified with FISH/SISH in all 14 cases. 9/14 tumors were 3+ IHC positive (64%) and 3 cases were 2+ IHC positive. In our cohort the CEP17 amplicon almost always involves the HER2 but not the TOP2 locus. Overall agreement on HER2/CEP17 ratio (when applying ASCO/CAP guidelines) was only 64% (9/14 cases) between the institutions. Discrepant ratios varied from 1.1 to 14.3. The HER2/CEP17 co-amplification is not defined in the ASCO/CAP guidelines, and may result in inaccurate HER2-FISH/SISH status, particularly if only the calculated HER2/CEP17 ratio is reported. It is recommended to report separate CEP17 and HER2 signals in complex HER2/CEP17 patterns.

MeSH terms

  • Adult
  • Aged
  • Antigens, Neoplasm / genetics
  • Breast Neoplasms / diagnosis
  • Breast Neoplasms / genetics*
  • Carcinoma, Ductal, Breast / diagnosis
  • Carcinoma, Ductal, Breast / genetics*
  • Centromere / genetics*
  • Chromosomes, Human, Pair 17 / genetics*
  • DNA Copy Number Variations
  • DNA Topoisomerases, Type II / genetics
  • DNA-Binding Proteins / genetics
  • Diagnostic Errors
  • Female
  • Gene Amplification*
  • Humans
  • In Situ Hybridization, Fluorescence
  • Middle Aged
  • Poly-ADP-Ribose Binding Proteins
  • Receptor, ErbB-2 / genetics*
  • Receptors, Retinoic Acid / genetics
  • Retinoic Acid Receptor alpha
  • Retrospective Studies
  • Tumor Suppressor Protein p53 / genetics


  • Antigens, Neoplasm
  • DNA-Binding Proteins
  • Poly-ADP-Ribose Binding Proteins
  • RARA protein, human
  • Receptors, Retinoic Acid
  • Retinoic Acid Receptor alpha
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • ERBB2 protein, human
  • Receptor, ErbB-2
  • DNA Topoisomerases, Type II
  • TOP2A protein, human