Epidermal growth factor receptor gene amplification and protein overexpression in basal-like carcinoma of the breast

Shao M‐M, Zhang F, Meng G, Wang X‐X, Xu H, Yu X‐W, Chen L‐Y & Tse G M
(2011) Histopathology 59 , 264–273 Epidermal growth factor receptor gene amplification and protein overexpression in basal‐like carcinoma of the breast Aims: Epidermal growth factor receptor (EGFR) is frequently expressed in basal‐like breast cancer (BLBC). The aim of this study was to evaluate their correlation as detected by immunohistochemistry (IHC) or fluorescence in‐situ hybridization (FISH). Methods and results: IHC for oestrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor (HER) 2, cytokeratin (CK) 5/6 and EGFR, and FISH for EGFR amplification, were performed in 59 cases of BLBC. EGFR IHC results were scored semiquantitatively, and compared with its gene amplification status. ER, PR and HER2 were negative in all cases, whereas 35 and 55 cases were positive for CK5/6 and EGFR. For EGFR IHC, 20, 11, 11 and 17 cases showed a negative, a low, an intermediate or a high staining level, respectively, and seven cases showed gene amplification by FISH, with two, 19, 11 and 20 cases showing balanced monosony, disomy, trisomy, and polysomy respectively. Immunohistochemical expression in gene‐amplified tumours was significantly higher than in those without amplification, including balanced polysomy tumours. EGFR immunohistochemical expression also correlated with the EGFR/chromosome 7 ratio. High sensitivity (86%) and negative predictive value (98%) were achieved with high‐level immunohistochemical expression as a cut‐off to predict gene amplification. Conclusions: High‐level EGFR immunohistochemical expression correlated with and predicted EGFR amplification, and may be used as a screening method to exclude gene amplification.