Comparison of immunohistochemistry with fluorescence in situ hybridization in determining the human epidermal growth factor receptor 2 status of breast cancer specimens: a multicenter study of 3,149 Chinese patients.
BACKGROUND
Accurate detection of human epidermal growth factor receptor 2 (HER2) expression and gene amplification is crucial for the application of HER2-specific therapy and for evaluating the response of patients with breast cancer. A uniform and standard procedure of immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) needs to be established for evaluating the HER2 status in breast cancer tissues for the treatment of patients with real HER2-positive tumors. The present multicenter study was aimed to examine the HER2 status in breast cancer specimens from Chinese patients using both IHC and FISH methods.


METHODS
A multicenter study was performed on the HER2 status in 3 149 breast cancer specimens from different ethnic populations and areas in China by IHC and FISH assays. The potential association of HER2 status with demographic and clinical characteristics was analyzed.


RESULTS
The positive rates for HER2 over-expression and HER2 amplification were 23.3% and 27.5% in this study, respectively. The concordance between IHC and FISH was 71.2% (κ = 0.494, P < 0.001). Furthermore, 72.9% of specimens with IHC 2+ were negative to FISH. The discordance rates among laboratories were from 5% to 28% for IHC and 1% to 16% for FISH. HER2 amplification was associated significantly with advanced tumor stage (III or IV, P = 0.002), large tumor size (>5 cm, P = 0.002), moderate and poor histological grades (P < 0.0001), post-menopause (P < 0.0001), ER-PR- (P = 0.002), and having ≥ 4 lymph nodes affected (P < 0.0001) in this population. The positive rates of HER2 amplification in specimens from Man and Hui Chinese were significantly higher than that in other Chinese populations. There are slightly higher positive rates of HER2 expression and amplification in Chinese patients with breast cancer.


CONCLUSIONS
These findings may provide new insights into understanding the epidemiological features of HER2 expression and amplification, and may be valuable for clinical practice.
Department of Medical Oncology, Beijing Key Laboratory of Clinical Study on Anti-cancer Molecular Targeted Drugs, Cancer Institute/Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100021, China.
Xiaohong
X
Han
Department of Medical Oncology, Beijing Key Laboratory of Clinical Study on Anti-cancer Molecular Targeted Drugs, Cancer Institute/Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100021, China.
Yuankai
Y
Shi
Department of Medical Oncology, Beijing Key Laboratory of Clinical Study on Anti-cancer Molecular Targeted Drugs, Cancer Institute/Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100021, China.
Li
L
Ma
Department of Medical Oncology, Beijing Key Laboratory of Clinical Study on Anti-cancer Molecular Targeted Drugs, Cancer Institute/Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100021, China.
Zheng
Z
Lyu
Department of Pathology, Cancer Institute/Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100021, China.
Hongying
H
Yang
Department of Medical Oncology, Beijing Key Laboratory of Clinical Study on Anti-cancer Molecular Targeted Drugs, Cancer Institute/Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100021, China.
Jiarui
J
Yao
Department of Medical Oncology, Beijing Key Laboratory of Clinical Study on Anti-cancer Molecular Targeted Drugs, Cancer Institute/Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100021, China.
Jian
J
Li
Department of Medical Oncology, Beijing Key Laboratory of Clinical Study on Anti-cancer Molecular Targeted Drugs, Cancer Institute/Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100021, China.
Bo
B
Li
Department of Medical Oncology, Beijing Key Laboratory of Clinical Study on Anti-cancer Molecular Targeted Drugs, Cancer Institute/Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100021, China.
Yan
Y
Qin
D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D001943:Breast Neoplasms / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods*; D017404:In Situ Hybridization, Fluorescence / Q000379:methods*; D008875:Middle Aged; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis* / Q000235:genetics / Q000378:metabolism
D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human