PMID- 30284063
OWN - NLM
STAT- MEDLINE
DCOM- 20190114
LR  - 20200309
IS  - 1559-131X (Electronic)
IS  - 1357-0560 (Print)
IS  - 1357-0560 (Linking)
VI  - 35
IP  - 12
DP  - 2018 Oct 3
TI  - Droplet digital PCR using HER2/EIF2C1 ratio for detection of HER2 amplification 
      in breast cancer tissues.
PG  - 149
LID - 10.1007/s12032-018-1210-8 [doi]
LID - 149
AB  - Breast cancers with amplification and overexpression of human epithelial growth 
      factor receptor 2 (HER2) are associated with poor prognosis, and targeted for 
      anti-HER2 therapy. Immunohistochemistry (IHC) and fluorescence in situ 
      hybridization (FISH) are currently the recommended methods to asses HER2 
      overexpression/amplification. Droplet digital PCR (ddPCR), a highly accurate 
      method to quantify DNA copy number, is potentially a robust alternative for HER2 
      diagnostics. In the FISH assay and most of previous ddPCR reports, chromosome 17 
      centromere (CEP17) has been used as the reference control to determine HER2/CEP17 
      ratio. Nevertheless, miss-classification could occur when HER2 is co-amplified 
      with CEP17. To avoid this inherent defect, in the present study, we employed 
      ddPCR assay using the human eukaryotic translation initiation factor 2C1 (EIF2C1) 
      gene located at chromosome 1p34.3 as the reference control to quantify HER2 copy 
      number in 31 frozen breast cancer tissues. HER2 status of these samples had been 
      determined by FISH and classified as HER2-amplified and HER2-non-amplified breast 
      cancers. The results showed that HER2 determined by ddPCR using HER2/EIF2C1 ratio 
      was in good concordance with HER2 determined by FISH using HER2/CEP17 ratio, the 
      concordance rate 87.1% (27/31), Kappa  = 0.719. The sensitivity and specificity 
      of ddPCR assay was 90% (9/10) and 85.7% (18/21), respectively. The median 
      HER2/EIF2C1 copy number ratio in HER2-amplified cancers (6.55, range 1.3-17.3) 
      was significantly higher than in HER2-non-amplified cancers (1.05, range 0.6-3.6, 
      p < 0.001). This study demonstrated that ddPCR using HER2/EIF2C1 ratio could 
      accurately assess HER2 status in frozen breast cancer tissues. Thus, our findings 
      warrant further studies into breast cancer with HER2-equivocal by IHC/FISH.
FAU - Tantiwetrueangdet, Anchalee
AU  - Tantiwetrueangdet A
AD  - Research Center, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, 
      Bangkok, Thailand.
FAU - Panvichian, Ravat
AU  - Panvichian R
AUID- ORCID: 0000-0001-5282-8166
AD  - Department of Internal Medicine, Division of Medical Oncology, Faculty of 
      Medicine, Ramathibodi Hospital, Mahidol University, Rama 6 Road, Rajthevi, 
      Bangkok, 10400, Thailand. ravat.pan@mahidol.ac.th.
FAU - Wongwaisayawan, Sansanee
AU  - Wongwaisayawan S
AD  - Department of Pathology, Faculty of Medicine, Ramathibodi Hospital, Mahidol 
      University, Bangkok, Thailand.
FAU - Sueangoen, Natthaporn
AU  - Sueangoen N
AD  - Research Center, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, 
      Bangkok, Thailand.
FAU - Lertsithichai, Panuwat
AU  - Lertsithichai P
AD  - Department of Surgery, Faculty of Medicine, Ramathibodi Hospital, Mahidol 
      University, Bangkok, Thailand.
LA  - eng
PT  - Journal Article
DEP - 20181003
PL  - United States
TA  - Med Oncol
JT  - Medical oncology (Northwood, London, England)
JID - 9435512
RN  - 0 (AGO1 protein, human)
RN  - 0 (Argonaute Proteins)
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (Eukaryotic Initiation Factors)
RN  - EC 2.7.10.1 (ERBB2 protein, human)
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
SB  - IM
MH  - Argonaute Proteins/*genetics
MH  - Biomarkers, Tumor/*genetics
MH  - Breast Neoplasms/*diagnosis/genetics
MH  - Eukaryotic Initiation Factors/*genetics
MH  - Female
MH  - *Gene Amplification
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Middle Aged
MH  - Polymerase Chain Reaction/*methods
MH  - Prognosis
MH  - Receptor, ErbB-2/*genetics
PMC - PMC6182624
OTO - NOTNLM
OT  - EIF2C1
OT  - FISH
OT  - HER2
OT  - IHC
OT  - ddPCR
COIS- CONFLICT OF INTEREST: The authors declare no conflict of interests regarding the 
      publication of this paper. ETHICAL APPROVAL: This study was approved by the 
      Ethics Committee on Research involving Human Subjects of the Faculty of Medicine, 
      Ramathibodi Hospital, Mahidol University. INFORMED CONSENT: As this retrospective 
      study was observational and link anonymized, no patient informed consent was 
      required.
EDAT- 2018/10/05 06:00
MHDA- 2019/01/15 06:00
PMCR- 2018/10/03
CRDT- 2018/10/05 06:00
PHST- 2018/09/05 00:00 [received]
PHST- 2018/09/26 00:00 [accepted]
PHST- 2018/10/05 06:00 [entrez]
PHST- 2018/10/05 06:00 [pubmed]
PHST- 2019/01/15 06:00 [medline]
PHST- 2018/10/03 00:00 [pmc-release]
AID - 10.1007/s12032-018-1210-8 [pii]
AID - 1210 [pii]
AID - 10.1007/s12032-018-1210-8 [doi]
PST - epublish
SO  - Med Oncol. 2018 Oct 3;35(12):149. doi: 10.1007/s12032-018-1210-8.