PMID- 26856369
OWN - NLM
STAT- MEDLINE
DCOM- 20170116
LR  - 20181113
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 6
DP  - 2016 Feb 9
TI  - Continuous quantification of HER2 expression by microfluidic precision 
      immunofluorescence estimates HER2 gene amplification in breast cancer.
PG  - 20277
LID - 10.1038/srep20277 [doi]
LID - 20277
AB  - Chromogenic immunohistochemistry (IHC) is omnipresent in cancer diagnosis, but 
      has also been criticized for its technical limit in quantifying the level of 
      protein expression on tissue sections, thus potentially masking clinically 
      relevant data. Shifting from qualitative to quantitative, immunofluorescence (IF) 
      has recently gained attention, yet the question of how precisely IF can quantify 
      antigen expression remains unanswered, regarding in particular its technical 
      limitations and applicability to multiple markers. Here we introduce microfluidic 
      precision IF, which accurately quantifies the target expression level in a 
      continuous scale based on microfluidic IF staining of standard tissue sections 
      and low-complexity automated image analysis. We show that the level of HER2 
      protein expression, as continuously quantified using microfluidic precision IF in 
      25 breast cancer cases, including several cases with equivocal IHC result, can 
      predict the number of HER2 gene copies as assessed by fluorescence in situ 
      hybridization (FISH). Finally, we demonstrate that the working principle of this 
      technology is not restricted to HER2 but can be extended to other biomarkers. We 
      anticipate that our method has the potential of providing automated, fast and 
      high-quality quantitative in situ biomarker data using low-cost 
      immunofluorescence assays, as increasingly required in the era of individually 
      tailored cancer therapy.
FAU - Dupouy, Diego G
AU  - Dupouy DG
AD  - Laboratory of Microsystems, Ecole Polytechnique Federale de Lausanne, CH-1015, 
      Switzerland.
FAU - Ciftlik, Ata Tuna
AU  - Ciftlik AT
AD  - Laboratory of Microsystems, Ecole Polytechnique Federale de Lausanne, CH-1015, 
      Switzerland.
AD  - Lunaphore Technologies SA, EPFL Innovation Park-Building C, CH-1015, Lausanne, 
      Switzerland.
FAU - Fiche, Maryse
AU  - Fiche M
AD  - Institute of Pathology, Centre Hospitalier Universitaire Vaudois and University 
      of Lausanne, CH-1011 Lausanne, Switzerland.
FAU - Heintze, Deborah
AU  - Heintze D
AD  - Laboratory of Microsystems, Ecole Polytechnique Federale de Lausanne, CH-1015, 
      Switzerland.
AD  - Lunaphore Technologies SA, EPFL Innovation Park-Building C, CH-1015, Lausanne, 
      Switzerland.
FAU - Bisig, Bettina
AU  - Bisig B
AD  - Institute of Pathology, Centre Hospitalier Universitaire Vaudois and University 
      of Lausanne, CH-1011 Lausanne, Switzerland.
FAU - de Leval, Laurence
AU  - de Leval L
AD  - Institute of Pathology, Centre Hospitalier Universitaire Vaudois and University 
      of Lausanne, CH-1011 Lausanne, Switzerland.
FAU - Gijs, Martin A M
AU  - Gijs MA
AD  - Laboratory of Microsystems, Ecole Polytechnique Federale de Lausanne, CH-1015, 
      Switzerland.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20160209
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (Biomarkers, Tumor)
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
SB  - IM
MH  - Biomarkers, Tumor/*genetics/metabolism
MH  - Breast Neoplasms/*genetics/metabolism
MH  - Female
MH  - Fluorescent Antibody Technique
MH  - *Gene Amplification
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Microfluidics/*instrumentation/*methods
MH  - Pilot Projects
MH  - Receptor, ErbB-2/*genetics/metabolism
PMC - PMC4746572
COIS- A.T.C. and D.H., at the submission of the paper, are employed at Lunaphore 
      Technologies SA, which is commercializing the MTP-based technology. Some of the 
      authors have equity interest in Lunaphore Technologies SA.
EDAT- 2016/02/10 06:00
MHDA- 2017/01/17 06:00
PMCR- 2016/02/09
CRDT- 2016/02/10 06:00
PHST- 2015/08/14 00:00 [received]
PHST- 2015/12/23 00:00 [accepted]
PHST- 2016/02/10 06:00 [entrez]
PHST- 2016/02/10 06:00 [pubmed]
PHST- 2017/01/17 06:00 [medline]
PHST- 2016/02/09 00:00 [pmc-release]
AID - srep20277 [pii]
AID - 10.1038/srep20277 [doi]
PST - epublish
SO  - Sci Rep. 2016 Feb 9;6:20277. doi: 10.1038/srep20277.