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Equivocal (HER2 IHC 2+) breast carcinomas: gene–protein assay testing reveals association between genetic heterogeneity, individual cell amplification status and potential treatment benefits
Author(s) -
Pekar Gyula,
Kasselaki Ionna,
PekarLukacs Agnes,
Dekany Csaba,
Hellberg Dan,
Tot Tibor
Publication year - 2019
Publication title -
histopathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.626
H-Index - 124
eISSN - 1365-2559
pISSN - 0309-0167
DOI - 10.1111/his.13733
Subject(s) - immunohistochemistry , chromosome 17 (human) , breast carcinoma , breast cancer , gene duplication , pathology , carcinoma , biology , genetic heterogeneity , medicine , gene , chromosome , cancer , oncology , cancer research , genetics , phenotype
Aims Genetic heterogeneity can pose a challenge to identifying eligible cases for targeted therapy in the human epidermal growth factor receptor 2 ( HER 2) immunohistochemistry ( IHC ) 2+ breast carcinoma group. In this study, we characterised this subset of tumours according to clinicopathological parameters. Methods and results We assessed 1000 tumour cells per case and recorded the number of HER 2 and chromosome enumeration probe 17 ( CEP 17) copies using gene–protein assay slides. HER 2 status was determined based on ASCO / CAP 2013 guidelines. Tumours with 5–50% of cancer cells with amplification were considered to be heterogeneous, whereas those with >50% were considered to be non‐heterogeneous. In a study cohort of 110 HER 2 IHC 2+ carcinomas, 93 (84.5%) were non‐amplified, 12 (10.9%) were amplified and five (4.5%) were ISH ‐equivocal. All the HER 2‐amplified and two of ISH ‐equivocal cases (12.7%) corresponded to non‐heterogeneous tumours, with highly significant differences evident in the average HER 2/ CEP 17 ratio ( P = 0.0002) and the proportion of cells with HER 2 >6 copies ( P < 0.0001) compared with heterogeneous lesions. NST grade 3 and HER 2‐amplified carcinomas average HER 2/ CEP 17 ratio correlated with an increased number of cells with HER 2/ CEP 17 ≥2.0 ( P < 0.014). Triple‐negative CEP 17 polysomic carcinomas showed increased metastatic capacity ( P = 0.003) compared with other tumour types. Conclusion Non‐heterogeneous HER 2 IHC 2+ tumours tend to be HER 2‐amplified. Adding the percentage of cells with HER 2 >6 copies to the average HER 2/ CEP 17 ratio may facilitate assessment of amplification status in ISH ‐equivocal cases. The proportion of cells with HER 2/ CEP 17 ≥2.0 contributes information concerning the actual average HER 2/ CEP 17 ratio, depending on tumour type.