HER2 gene amplification in patients with breast cancer with equivocal IHC results

• Published in: Journal of clinical pathology Vol. 64; no. 12; pp. 1069 - 1072
• Main Authors: Meijer, Sybren L, Wesseling, Jelle, Smit, Vincent T, Nederlof, Petra M, Hooijer, Gerrit K J, Ruijter, Henrique, Arends, Jan Willem, Kliffen, Mike, van Gorp, Joost M, Sterk, Lotus, van de Vijver, Marc J
• Format: Journal Article
• Language: English
• Published: London BMJ Publishing Group Ltd and Association of Clinical Pathologists 01.12.2011; BMJ Publishing Group; BMJ Publishing Group LTD
• Subjects: Biological and medical sciences; Breast cancer; Breast Neoplasms - genetics; breast pathology; cancer genetics; cancer research; Cancer therapies; cerb 2; Chemotherapy; Chromosomes; CISH; colorectal cancer; comparative genomic hybridisation; diagnostics; equivocal test result; familial cancers; Female; gall bladder; Gene amplification; Gene Amplification - genetics; Genes, erbB-2 - genetics; GI neoplasms; gynaecological pathology; Gynecology. Andrology. Obstetrics; HER2; Humans; image analysis; immunocytochemistry; Immunohistochemistry; in situ hybridisation; In Situ Hybridization - methods; Investigative techniques, diagnostic techniques (general aspects); Kinases; Laboratories; Mammary gland diseases; Medical prognosis; Medical sciences; molecular oncology; molecular pathology; oncology; p53; pancreas; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; Protein expression; Proteins; Tumors; California; Human; Mammary gland diseases; Gene amplification; Anatomic pathology; Breast disease; erbB2 Gene; Breast cancer; Malignant tumor; Cancer
• DOI: 10.1136/jclinpath-2011-200019
• ISSN: 0021-9746; 1472-4146

AimsEquivocal 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.Methods553 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.ResultsUsing 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).ConclusionsTesting 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.