HER2 FISH results in breast cancers with increased CEN17 signals using alternative chromosome 17 probes - reclassifying cases in the equivocal category.

ABSTRACT: AIMS: HER2 testing of invasive breast cancer by in-situ hybridisation guides therapy decisions. Probing HER2 and cen17 simultaneously is supposed to reveal both a potential HER2 gene amplification and polysomy 17. However, a considerable number of breast cancer patients with quasi polysomy 17 are considered "equivocal" which is diagnostically meaningless. Moreover, patients with equivocal / false polysomic tumours are prevented from a potentially beneficial anti-HER2 treatment. Here we evaluated the RAI1, D17S122, and TP53 hybridisation markers to reliably indicate true polysomy and to accurately reclassify equivocal samples as HER2-positive. METHODS AND RESULTS: Samples with (n = 82) and without (n = 52) increased cen17 copy numbers and 78 evidently HER2-amplified specimens were analysed using dual and triple marker hybridisation probes. Selected putative polysomic samples were subjected to array-based comparative genomic hybridisation. We found that 37.8% samples with putative polysomy 17 did not show any gain in RAI1, D17S122, or TP53. Accordingly, aCGH revealed evidence for the presence of HER2/cen17 coamplification rather than for true polysomy in those cases. Reflex testing using alternate 17p markers reclassified up to 56.3% equivocal cases as HER2-positive and the combined assessment of a 17p and 17q locus allows the differentiation of true vs. false polysomy. CONCLUSIONS: An increased cen17 copy number does not necessarily reflect polysomy and reflex testing facilitates the reclassification of "equivocals". Nevertheless, the prognostic and predictive value of a HER2/cen17 coamplification versus HER2 gene amplification alone must still be prospectively evaluated. This article is protected by copyright. All rights reserved.

ORGANISM(S): Homo sapiens

PROVIDER: GSE86305 | GEO | 2017/01/01

SECONDARY ACCESSION(S): PRJNA341380

REPOSITORIES: GEO