title: Quantum dot-based immunofluorescent imaging of Ki67 and identification of prognostic value in HER2-positive (non-luminal) breast cancer.
abstract: BACKGROUND
  The immunohistochemical assessment of Ki67 antigen (Ki67) is the most widely practiced measurement of breast cancer cell proliferation; however, it has some disadvantages and thus the prognostic value of Ki67 in breast cancer remains controversial. Our previous studies confirmed the advantages of quantum dots-based nanotechnology for quantitative analysis of biomarkers compared with conventional immunohistochemistry (IHC). This study was designed to assess Ki67 by quantum dot-immunohistochemistry (QD-IHC) and investigate the prognostic value of the Ki67 score in human epidermal growth factor receptor 2 (HER2)-positive (non-luminal) breast cancer.
  
  
  METHODS
  Ki67 expression in 108 HER2-positive (non-luminal) breast cancer specimens was detected by IHC and QD-IHC. Two observers assessed the Ki67 score independently and comparisons between the two methods were made. The prognostic value of the Ki67 score for five-year disease-free survival was estimated.
  
  
  RESULTS
  The same antigen localization, high correlation of staining rates (r=0.993), and high agreement of measurements (κ=0.874) of Ki67 expression (cutoff: 30%) in breast cancer were found by QD-IHC and conventional IHC. The QD-IHC had a better interobserver agreement for the Ki67 score than conventional IHC (t=-7.280, P<0.01). High Ki67 expression (cutoff: 30%) was associated with shorter disease-free survival (log-rank test; IHC, P=0.026; QD-IHC, P=0.001), especially in the lymph node-negative subgroups (log-rank test; IHC, P=0.017; QD-IHC, P=0.002).
  
  
  CONCLUSIONS
  QD-IHC imaging of Ki67 was an easier and more accurate method for detecting and assessing Ki67. The Ki67 score was an independent prognosticator in the HER2-positive (non-luminal) breast cancer patients.
authors.affiliation: Department of Breast and Thyroid Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, People's Republic of China.
authors.forename: Jin-Zhong
authors.initials: JZ
authors.lastname: Sun
authors.affiliation: Department of Breast and Thyroid Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, People's Republic of China.
authors.forename: Chuang
authors.initials: C
authors.lastname: Chen
authors.affiliation: Department of Dermatology, Renmin Hospital of Wuhan University, Wuhan, Hubei, People's Republic of China.
authors.forename: Guan
authors.initials: G
authors.lastname: Jiang
authors.affiliation: Department of Biomedical Engineering, Wuhan University School of Basic Medical Sciences, Wuhan, Hubei, People's Republic of China.
authors.forename: Wei-Qun
authors.initials: WQ
authors.lastname: Tian
authors.affiliation: Department of Oncology, Zhongnan Hospital of Wuhan University and Hubei Key Laboratory of Tumor Biological Behaviors and Hubei Cancer Clinical Study Center, Wuchang District, Wuhan, Hubei, People's Republic of China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Breast and Thyroid Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, People's Republic of China.
authors.forename: Sheng-Rong
authors.initials: SR
authors.lastname: Sun
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000378:metabolism*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism*; D008875:Middle Aged; D050997:Nanomedicine; D036103:Nanotechnology; D011379:Prognosis; D045663:Quantum Dots; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*
chemical_list: D019394:Ki-67 Antigen; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human
keywords: Ki67; breast cancer; disease-free survival; prognosis; quantum dots