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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
Lund Univ, Dept Oncol & Pathol, Solvegatan 25, Lund, Sweden.ORCID iD: 0000-0002-0667-0270
Lund Univ, Dept Oncol & Pathol, Solvegatan 25, Lund, Sweden.
Lund Univ, Dept Oncol & Pathol, Solvegatan 25, Lund, Sweden.ORCID iD: 0000-0001-7776-4744
Lund Univ, Dept Oncol & Pathol, Solvegatan 25, Lund, Sweden.
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2019 (English)In: Histopathology, ISSN 0309-0167, E-ISSN 1365-2559, Vol. 74, no 2, p. 300-310Article in journal (Refereed) Published
Abstract [en]

Aims: Genetic heterogeneity can pose a challenge to identifying eligible cases for targeted therapy in the human epidermal growth factor receptor 2 (HER2) 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 HER2 and chromosome enumeration probe 17 (CEP17) copies using gene-protein assay slides. HER2 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 HER2 IHC 2+ carcinomas, 93 (84.5%) were non-amplified, 12 (10.9%) were amplified and five (4.5%) were ISH-equivocal. All the HER2-amplified and two of ISH-equivocal cases (12.7%) corresponded to non-heterogeneous tumours, with highly significant differences evident in the average HER2/CEP17 ratio (P = 0.0002) and the proportion of cells with HER2 >6 copies (P < 0.0001) compared with heterogeneous lesions. NST grade 3 and HER2-amplified carcinomas average HER2/CEP17 ratio correlated with an increased number of cells with HER2/CEP17 >= 2.0 (P < 0.014). Triple-negative CEP17 polysomic carcinomas showed increased metastatic capacity (P = 0.003) compared with other tumour types.

Conclusion: Non-heterogeneous HER2 IHC 2+ tumours tend to be HER2-amplified. Adding the percentage of cells with HER2 >6 copies to the average HER2/CEP17 ratio may facilitate assessment of amplification status in ISH-equivocal cases. The proportion of cells with HER2/CEP17 >= 2.0 contributes information concerning the actual average HER2/CEP17 ratio, depending on tumour type.

Place, publisher, year, edition, pages
WILEY , 2019. Vol. 74, no 2, p. 300-310
Keywords [en]
ASCO/CAP guidelines, breast cancer, gene-protein assay, HER2 IHC 2+, heterogeneity
National Category
Cancer and Oncology Cell and Molecular Biology
Identifiers
URN: urn:nbn:se:uu:diva-373315DOI: 10.1111/his.13733ISI: 000453895100011PubMedID: 30113715OAI: oai:DiVA.org:uu-373315DiVA, id: diva2:1279369
Available from: 2019-01-16 Created: 2019-01-16 Last updated: 2019-01-16Bibliographically approved

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Hellberg, Dan

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