Immunohistochemical and molecular analyses of HER2 status in breast cancers are highly concordant and complementary approaches |
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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 |
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Affiliation: | AP-HP, Hosp Saint-Louis, Department of Biochemistry, Paris 75010, France. jacqueline.lehmann-che@sls.aphp.fr |
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Abstract: | 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. |
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Keywords: | HER2 HER2/neu ERBB2 c-erb-b2 heterogeneity real-time PCR |
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