ABSTRACT
BACKGROUND: Accurate HER2 testing is of great clinical value for the identification of breast cancer patients who are eligible for trastuzumab therapy. The aim of this study is to review breast carcinomas diagnosed from 2001 to 2007 at a Spanish National Reference Centre for HER2 testing, evaluating the agreement between HER2 immunohistochemical (IHC) tests and fluorescence in situ hybridisation (FISH) tests. METHODS: Demographic and clinical information was obtained from 2751 breast carcinoma patients. HER2 IHC and FISH tests were performed both in a local laboratory and in the reference centre. The HER2 IHC0/1+, IHC2+, IHC3+ and FISH-positive patients comprised 64%, 20%, 16% and 24% of the available population, respectively (results from the reference centre). Using statistical approaches, we evaluated the agreement between: (1) HER2 IHC and FISH tests, and (2) results provided by the local and the reference laboratories. RESULTS: The data confirmed a statistically significant relation between HER2 overexpression and amplification. We also found that instances of polysomy 17 and heterogeneous patterns of HER2 expression (heterogeneous staining distribution in different areas of the same tumour) are more frequently observed in HER2-positive tumours. Finally, since the diagnoses were made from 2001 to 2007, we could also observe a rising agreement rate between laboratories/pathologists with time. CONCLUSIONS: HER2 testing is most accurate when performed by experienced pathologists and at a high-volume reference laboratory. Polysomy 17 and HER2 heterogeneous staining patterns should also be considered for a better understanding of the variation in the anti-HER2 therapeutic response.