Intratumoral heterogeneity of HER2 status in breast carcinoma

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

“…In such situations, following other recommendations, an absolute HER2 gene copy count of [6 will fulfill the criteria for a HER2 positive status in all cases (100%) [16,25,27]. Although not included in the ASCO/CAP guidelines, there are papers that propagate their 'own made' criteria, at least for the numeration of the HER2 gene in the case of cluster formation.…”

“…8) showed 1037 HER2 and 1007 CEP17 signals. The HER2 gene count of 17.28 would imply amplification, whereas the CEP17 gene count of 16.78 would mean high chromosomal gain using the recommendations suggested by Viale et al in his discussion for real polysomic cases [16,25,27]. According to the ASCO/CAP guidelines on the other hand, this case is classified as non-amplified as the HER2/CEP17 ratio is 'only' 1.03 [12,30].…”

“…We used the criteria mentioned above in the guidelines for the in situ hybridization for all the gene regions [16,25,27]. In one institute, the exact method of counting required an electronic excel data sheet as described in previous publications [16,25,27]. The other two institutions used direct counting on the computer screen and/or on the fluorescence microscope.…”

“…If more than 50% of the invasive tumor cells in these areas had a HER2/CEP17 ratio higher than 2.2, we considered the tumor as amplified. We used these criteria to examine all the gene regions named above: HER2, CEP17, RARA, TOP2, and TP53 [16,25,27].…”

“…In 9 of 14 cases (64%) the institutions reached an agreement on the HER2 status as amplified or non-amplified, even though the individual ratios varied. We used the criteria mentioned above in the guidelines for the in situ hybridization for all the gene regions [16,25,27]. In one institute, the exact method of counting required an electronic excel data sheet as described in previous publications [16,25,27].…”