The Clinicopathologic and Prognostic Value of Altered Chromosome 17 Centromere Copy Number in HER2 Fish Equivocal Breast Carcinomas

Abstract

Chromosome 17 centromere (CEP17) gain is frequently observed in breast cancer by fluorescence in situ hybridization (FISH). To address the biologic characteristics and clinical significance of CEP17 gain in a large population of breast cancer patients, we performed FISH on a series of 770 breast cancer tissues to evaluate the status of human epidermal growth factor receptor 2 (HER2) gene and CEP17 by immunohistochemistry (IHC) and FISH. Among the 770 specimens, 184 cases showed CEP17 gain (23.9%). Histological grade, nodal status, HER2 by IHC, Ki 67 index, and p53 expression were significantly different between CEP17 gain tumors and HER2-positive tumors. In contrast with HER2-negative tumors, CEP17 gain tumors showed higher histological grade, higher HER2 score by IHC, and higher Ki 67 index. The patients with CEP17 gain tumors had an intermediate survival between HER2-negative and HER2-positive patients. By comparison to HER2-negative and HER2-positive patients, survival in luminal B patients with CEP17 gain tumors also fell in between. In conclusion, CEP17 gain tumors show specific differences compared with HER2-negative and HER2-positive tumors in clinical parameters and prognosis.

Impact of an alternative chromosome 17 probe and the 2013 American Society of Clinical Oncology and College of American Pathologists guidelines on fluorescence in situ hybridization for the determination of HER2 gene amplification in breast cancer

“…The majority of patients in this series who were reclassified from equivocal to amplified under the 2013 guidelines had pathologic stage I, intermediate to high histologic grade, hormone receptor‐positive, lymph node‐negative disease and received treatment with endocrine therapy, HER2‐targeted therapy, and chemotherapy. The clinicopathologic features of these tumors are not those typically expected for HER2 ‐amplified tumors, but they are similar to what has been reported for the “new equivocal” tumors defined by the 2013 guidelines . All of these tumors had an HER2:CEP17 ratio <2.0, a mean HER2 copy number between ≥4.0 and <6.0, and a mean CEP17 copy number ≥2.6.…”

“…The clinicopathologic features of these tumors are not those typically expected for HER2-amplified tumors, but they are similar to what has been reported for the "new equivocal" tumors defined by the 2013 guidelines. 25,31,34,38 All of these tumors had an HER2:CEP17 ratio <2.0, a mean HER2 copy number between 4.0 and <6.0, and a mean CEP17 copy number 2.6. These tumors also appeared to be enriched for equivocal (21) IHC results, similar to what has been reported by others for the equivocal category in the 2013 guidelines.…”

Clinicopathologic features of breast cancer reclassified as HER2-amplified by fluorescence in situ hybridization with alternative chromosome 17 probes

“…The clinicopathological characteristics of these tumors are not typical for HER2-amplified tumors but they are similar to the "excess" equivocal cases identified using the 2013 Guidelines. 19,25,28,35 These tumors also were unlikely to have positive (3+) IHC results, similar to the data from other studies of the equivocal category in the 2013 Guidelines. 15,18,19,21,22 The clinicopathologic features and HER2 IHC data may account for the fact that approximately 60% of patients in this series who were re-classified as amplified with alternative probes were not treated with HER2-targeted therapy.…”

HER2-directed antibodies, affibodies and nanobodies as drug-delivery vehicles in breast cancer with a specific focus on radioimmunotherapy and radioimmunoimaging

“…a Negative (score 0), b negative (score 1+), c equivocal (score 2+), d positive (score 3+). [6] antibody domain and are characterised by their low molecular weight of approximately 15 kDa and their fast blood clearance [28].…”