FISH testing of HER2 immunohistochemistry 1+ invasive breast cancer with unfavorable characteristics

Abstract

Diagnostic assays for human epidermal growth factor receptor 2 (HER2) expression have a high predictive value because patients with HER2‑positive tumors could benefit from HER2‑targeted therapy. The aim of the present study is to analyze the incidence of HER2 gene amplification in selected tumors with adverse features that scored 1+ by immunohistochemistry (IHC). For that purpose, 331 consecutive invasive breast cancers (IBCs) were tested by IHC for HER2 expression between January and December 2013, 102 of which (31%) scored 1+. Of these 102 women with IBC who underwent surgery, 75 entered the study (73.5%). A total of 48 out of 75 (64%) IBC samples (patients' median age, 60.75 years) were selected according to ≥1 unfavorable tumor characteristics, and tested by fluorescence in situ hybridization (FISH). Of these 48 IBC samples scoring 1+ by IHC, 22 (46%) exhibited high histological grade (G3), 23 (48%) had a high proliferative index (Ki‑67, >30%), 27 (56%) showed vascular invasion and 32 out of 41 evaluable cases (78%) were node‑positive. Regarding hormone receptor expression, 3 (6%) and 10 (21%) cases were negative for estrogen and progesterone receptors expression, respectively. FISH was performed on 48 IBC cases scoring 1+ by IHC, and 7 infiltrating ductal carcinomas (IDCs) (14.6%) demonstrated HER2 amplification with a high proliferative index. In 42 IDC samples, statistical analysis evidenced a significant association between histological grade and high proliferative index (P=0.0200). In addition, in 48 HER2 scoring 1+ IBCs, Fisher's exact test evidenced a significant association between the presence of gene amplification and high proliferative index (P=0.0033). Based on these biopathological parameters, particularly a high proliferative index, the present results indicate that it is possible to of identify tumors scoring 1+ by IHC with HER2 amplification by FISH, thus aiding the selection of patients who are suitable for HER2‑targeted therapy according to an acceptable cost/benefit ratio.