Aims: Equivocal human epidermal growth factor receptor 2 protein (HER2) (2+) immunohistochemistry (IHC) is subject to significant interobserver variation and poses a challenge in obtaining a definitive positive or negative test result. This equivocal test result group accounts for approximately 15% of all tumours, and for optimal guidance of HER2 targeted therapy, a further analysis of quantification of gene copy number and amplification status is needed for patients with early or metastatic breast cancer. Methods: 553 breast-cancer specimens with equivocal HER2 IHC(2+) test results were collected and subsequently centrally retested by chromogenic in situ hybridisation (CISH), and HER2 gene copy numbers per tumour cell nucleus were determined. Results: Using CISH, 77 of 553 equivocal HER2 IHC(2+) test result cases (13.9% of total) showed high levels of HER2 gene amplification (≥10.0 gene copies per nucleus), and 41 of 553 (7.4% of total) showed low-level HER2 gene amplification (6.0-9.9 gene copies per nucleus). In 73.6% of cases, no amplification of the HER2 gene was shown, and in only 4.9% of cases was an equivocal test result by CISH observed (4.0-5.9 gene copies per nucleus). Conclusions: Testing by CISH of all equivocal HER2 IHC (2+) test result provides a definitive guidance in HER2 targeted therapy in 95.1% of cases. A significant proportion (21.3%) of patients with equivocal IHC(2+) test results show amplification of the HER2 gene.

dx.doi.org/10.1136/jclinpath-2011-200019, hdl.handle.net/1765/65514
Journal of Clinical Pathology: an international peer-reviewed journal for health professionals and researchers in clinical pathology
Erasmus School of Law

Meijer, S, Wesseling, J, Smit, V.T.H.B.M, Nederlof, P.M, Hooijer, J, Ruijter, H, … Vijver, M.J. (2011). HER2 gene amplification in patients with breast cancer with equivocal IHC results. Journal of Clinical Pathology: an international peer-reviewed journal for health professionals and researchers in clinical pathology, 64(12), 1069–1072. doi:10.1136/jclinpath-2011-200019