Immunohistochemical and molecular analyses of HER2 status in breast cancers are highly concordant and complementary approaches

• Published in: British journal of cancer Vol. 104; no. 11; pp. 1739 - 1746
• Main Authors: Lehmann-Che, J, Amira-Bouhidel, F, Turpin, E, Antoine, M, Soliman, H, Legres, L, Bocquet, C, Bernoud, R, Flandre, E, Varna, M, de Roquancourt, A, Plassa, L-F, Giacchetti, S, Espié, M, de Bazelaire, C, Cahen-Doidy, L, Bourstyn, E, Janin, A, de Thé, H, Bertheau, P
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 24.05.2011; Nature Publishing Group
• Subjects: 631/1647/1513/2216; 631/1647/664/1257; 692/699/67/1347; Alleles; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Cancer Research; Drug Resistance; Epidemiology; Gene Dosage; Genes, erbB-2; Gynecology. Andrology. Obstetrics; Humans; Immunohistochemistry; In Situ Hybridization, Fluorescence; Mammary gland diseases; Medical sciences; Molecular Diagnostics; Molecular Medicine; Oncology; Receptors, Androgen; Reverse Transcriptase Polymerase Chain Reaction - methods; Tumors; HER2/neu; c-erb-b2; real-time PCR; HER2; heterogeneity; ERBB2; Immunohistochemistry; Breast disease; erbB2 Gene; Heterogeneity; Cancerology; Genetics; Reverse transcription polymerase chain reaction; Protooncogene; Quantitative analysis; Human; Breast cancer; Malignant tumor; Gene expression; Real time; Human Epidermal growth factor Receptor 2; Mammary gland diseases; Anatomic pathology; C-Onc gene; Molecular biology; Cancer
• ISSN: 0007-0920; 1532-1827; 1532-1827
• DOI: 10.1038/bjc.2011.135

Background: Immunohistochemistry (IHC) and fluorescent in situ hybridisation (FISH) are currently the most commonly used methods to assess HER2 status. PCR-based assays allow quantitative determination of HER2 amplification (Q-PCR) or overexpression (Q-RT–PCR), but are not routinely used. We evaluated the relevance of Q-RT–PCR for HER2 status determination. Methods: We compared IHC and Q-RT–PCR in 466 breast tumours. In discordant or equivocal cases, five additional methods (IHC with two other antibodies, FISH, silver in situ hybridisation (SISH) and Q-PCR) were combined to determine HER2 status. Two cases with HER2 intra-tumour heterogeneity were further explored by allelic profiles analysis and HUMARA clonality determination after microdissection. Results: We observed 97.3% concordance between Q-RT–PCR and non-equivocal IHC. Twelve out of 466 cases (3%) revealed discordances between the two methods. The power of Q-RT–PCR to predict HER2 status (defined by seven methods) was similar to that of IHC. Although rare, some discordances between techniques might be due to HER2 intra-tumour heterogeneity and we report two examples, one tumour containing two distinct clones, another tumour consisting of HER2 amplified and non-amplified subclones. Conclusion: Q-RT–PCR and IHC are highly concordant methods for HER2 status assessment, and Q-RT–PCR allows a highly reliable quantitative assessment and could be a useful adjunct to IHC.