[HER-2 overexpression and gene amplification of advanced breast cancers determined by fluorescence in situ hybridization in fine needle aspiration specimens].
OBJECTIVE
To explore the feasibility of testing HER-2 expression and gene amplification in fine needle aspiration specimens of advanced breast cancers, and to benefit the patients receiving targeted drug therapy.


METHODS
Liquid-based cytology specimens by fine needle aspiration of 49 breast cancer cases were used in this study. The expression of HER-2 protein was detected by immunocytochemistry (ICC) and the gene amplification was assessed by fluorescence in situ hybridization (FISH). All the 49 cases had overexpression of HER-2 protein marked as ++ or +++ in immunohistochemistry (IHC), and had corresponding FISH results in formalin-fixed, paraffin-embedded (FFPE) tissue samples.


RESULTS
FNA samples in all the 49 cases were tested by FISH, and showed a complete agreement with the FISH results in the histological specimens (kappa = 1.0). Of the 49 cases, 33 had HER-2 gene amplification in FFPE samples. So do that in FNA samples. Both had an amplification rate of 67.3%. Among the 33 cases with HER-2 gene amplification, 26 had an ICC score of +++ (78.8%). The conformity rate was 78.8%. Of the 33 cases, 29 had an IHC score of +++ (87.9%). Its conformity rate was 87.9%. The difference between the ICC and IHC results was statistically not significant (P = 0.322). Among the 16 cases with negative gene amplification by both ICC and IHC, 15 cases showed HER-2 protein expression as 0/+, and another one case was not counted because there was not enough cells. Of the 16 cases, 15 had an IHC score of ++ and one of +++ . To take the FISH results as gold standard, ICC results had a high sensitivity (87.9%) and specificity (100.0%).


CONCLUSIONS
FISH in FNA samples can be used in the clinic to test HER-2 gene amplification and overexpression in breast cancers, with a high sensitivity and specificity in ICC. Our data support the use of FISH and ICC analysis to determine HER-2 status on FNA specimens in patients with advanced breast cancer and recurrence or metastatic tumors. When ICC score is +++ , it indicates that there is a HER-2 gene amplification by FISH.
Department of Cytopathology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
Zhihui
Z
Zhang
Department of Cytopathology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
Linlin
L
Zhao
Department of Cytopathology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
Huiqin
H
Guo
Department of Cytopathology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
Lei
L
Guo
Department of Cytopathology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
Yun
Y
Ling
Department of Cytopathology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
Xin
X
Xu
Department of Cytopathology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
Huan
H
Zhao
Department of Cytopathology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China. Email: pqjing@hotmail.com.
Qinjing
Q
Pan
D000328:Adult; D000368:Aged; D044963:Biopsy, Fine-Needle; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D005260:Female; D005784:Gene Amplification; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008207:Lymphatic Metastasis; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D016612:Paraffin Embedding; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D012680:Sensitivity and Specificity
D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human