title: Clinicopathological variables predicting HER-2 gene status in immunohistochemistry-equivocal (2+) invasive breast cancer.
abstract: OBJECTIVE
  Human epidermal growth factor receptor-2 (HER-2) gene status is crucial to guide treatment decisions regarding the use of HER-2-targeted therapies in breast cancer. An invasive breast cancer with HER-2 2+ score is regarded as HER-2 status equivocal and should further determine by fluorescent in situ hybridization (FISH), which is considered the standard test for HER-2 status. Here, we aimed to establish a risk score to allow for prediction of the presence of HER-2 gene status.
  
  
  METHODS
  A total of 182 HER-2 2+ by immunohistochemistry (IHC) invasive breast cancer cases were enrolled in this study. The association between clinicopathological variables like age, sex, tumor grade, hormone receptor (HR) status, P53 and proliferation index (Ki67), and FISH result using US Food and Drug Administration (FDA) criteria was evaluated. Also, we compared the HER-2 FISH results using FDA criteria and 2013 American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guideline.
  
  
  RESULTS
  The study population had a median age of 48 years (range, 29-78 years). Estrogen receptor (ER) was expressed in 131 (72.0%) patients. 73.1% of patients (133/182) were progesterone receptor (PR) positive. The median Ki67 value was 20% (range, 3-90%). There was good agreement between the FDA and 2013 ASCO/CAP guideline. Sixty-three of all patients were HER-2 FISH amplified (positive) based on FDA criteria. Tumors with HER-2 amplified were more likely to harbor ER negative (58.8% vs. 25.2%, P<0.001) or PR negative (57.1% vs. 26.3%, P<0.001) or P53 negative (44.8% vs. 29.8%, P=0.048). A significant high level of Ki67 was detected in HER-2 amplified groups (P=0.006). We created a risk score that comprised HR, P53 and Ki67. A significant association between risk score and HER-2 FISH amplification was observed (χ(2)=30.41, P<0.001).
  
  
  CONCLUSIONS
  This novel immunohistochemical risk score could be highly useful to predict the presence of HER-2 gene status in invasive breast cancer.
authors.affiliation: 1 Department of Radiation Therapy, 2 Department of Pathology, 3 Department of Medical Oncology, Zhejiang Cancer Hospital, Hangzhou 310022, China.
authors.forename: Yongling
authors.initials: Y
authors.lastname: Ji
authors.affiliation: 1 Department of Radiation Therapy, 2 Department of Pathology, 3 Department of Medical Oncology, Zhejiang Cancer Hospital, Hangzhou 310022, China.
authors.forename: Liming
authors.initials: L
authors.lastname: Sheng
authors.affiliation: 1 Department of Radiation Therapy, 2 Department of Pathology, 3 Department of Medical Oncology, Zhejiang Cancer Hospital, Hangzhou 310022, China.
authors.forename: Xianghui
authors.initials: X
authors.lastname: Du
authors.affiliation: 1 Department of Radiation Therapy, 2 Department of Pathology, 3 Department of Medical Oncology, Zhejiang Cancer Hospital, Hangzhou 310022, China.
authors.forename: Guoqin
authors.initials: G
authors.lastname: Qiu
authors.affiliation: 1 Department of Radiation Therapy, 2 Department of Pathology, 3 Department of Medical Oncology, Zhejiang Cancer Hospital, Hangzhou 310022, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Chen
authors.affiliation: 1 Department of Radiation Therapy, 2 Department of Pathology, 3 Department of Medical Oncology, Zhejiang Cancer Hospital, Hangzhou 310022, China.
authors.forename: Xiaojia
authors.initials: X
authors.lastname: Wang
keywords: Invasive breast cancer; fluorescent in situ hybridization (FISH); human epidermal growth factor receptor-2 (HER-2); immunohistochemistry (IHC); prediction
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