PMID- 25323485
OWN - NLM
STAT- MEDLINE
DCOM- 20150727
LR  - 20231213
IS  - 1549-490X (Electronic)
IS  - 1083-7159 (Print)
IS  - 1083-7159 (Linking)
VI  - 19
IP  - 11
DP  - 2014 Nov
TI  - Gene status in HER2 equivocal breast carcinomas: impact of distinct 
      recommendations and contribution of a polymerase chain reaction-based method.
PG  - 1118-26
LID - 10.1634/theoncologist.2014-0195 [doi]
AB  - BACKGROUND: The primary objectives of this study on carcinomas with equivocal 
      HER2 expression were to assess the impact of distinct recommendations with regard 
      to identifying patients eligible for anti-HER2 agents by fluorescence in situ 
      hybridization (FISH) and to elucidate whether multiplex ligation-dependent probe 
      amplification (MLPA) may be of support in assessing HER2 gene status. METHODS: A 
      cohort of 957 immunohistochemistry-evaluated HER2-equivocal cases was analyzed by 
      dual-color FISH. The results were assessed according to U.S. Food and Drug 
      Administration (FDA) and European Medicines Agency (EMA) guidelines and American 
      Society of Clinical Oncology (ASCO) and College of American Pathologists (CAP) 
      2007 and 2013 guidelines for dual- and single-signal in situ hybridization (ISH) 
      assays. A subgroup of 112 cases was subjected to MLPA. RESULTS: HER2 
      amplification varied from 15% (ASCO/CAP 2007 HER2/CEP17 ratio) to 29.5% (FDA/EMA 
      HER2 copy number). According to the ASCO/CAP 2013 interpretation of the 
      dual-signal HER2 assay, ISH-positive carcinomas accounted for 19.7%. In contrast 
      with the ASCO/CAP 2007 ratio, this approach labeled as positive all 32 cases 
      (3.34%) with a HER2/CEP17 ratio <2 and an average HER2 copy number >/=6.0 signals 
      per cell. In contrast, only one case showing a HER2 copy number <4 but a ratio >/=2 
      was diagnosed as positive. MLPA data correlated poorly with FISH results because 
      of the presence of heterogeneous HER2 amplification in 33.9% of all amplified 
      carcinomas; however, MLPA ruled out HER2 amplification in 75% of ISH-evaluated 
      HER2-equivocal carcinomas. CONCLUSION: The ASCO/CAP 2013 guidelines seem to 
      improve the identification of HER2-positive carcinomas. Polymerase chain 
      reaction-based methods such as MLPA can be of help, provided that heterogeneous 
      amplification has been ruled out by ISH.
CI  - (c)AlphaMed Press.
FAU - Sapino, Anna
AU  - Sapino A
AD  - Department of Medical Sciences, University of Turin, Turin, Italy; Pathology 
      Unit, Department of Laboratory Medicine, Azienda Ospedaliera Citta della Salute e 
      della Scienza di Torino, Turin, Italy; Pathology Division, Santa Croce Hospital, 
      Moncalieri, Italy; Pathology Division, Azienda USL Valle d'Aosta, Aosta, Italy; 
      Pathology Division, Valdese Hospital, Turin, Italy; Pathology Division, Martini 
      Hospital, Turin, Italy; Pathology Division, ASL 9, Civile Hospital, Ivrea, Italy; 
      Department of Pathology, Regina Elena National Cancer Institute, Rome, Italy; 
      Division of Pathology, European Institute of Oncology, Milan, Italy; University 
      of Milan School of Medicine, Milan, Italy caterina.marchio@unito.it 
      anna.sapino@unito.it.
FAU - Maletta, Francesca
AU  - Maletta F
AD  - Department of Medical Sciences, University of Turin, Turin, Italy; Pathology 
      Unit, Department of Laboratory Medicine, Azienda Ospedaliera Citta della Salute e 
      della Scienza di Torino, Turin, Italy; Pathology Division, Santa Croce Hospital, 
      Moncalieri, Italy; Pathology Division, Azienda USL Valle d'Aosta, Aosta, Italy; 
      Pathology Division, Valdese Hospital, Turin, Italy; Pathology Division, Martini 
      Hospital, Turin, Italy; Pathology Division, ASL 9, Civile Hospital, Ivrea, Italy; 
      Department of Pathology, Regina Elena National Cancer Institute, Rome, Italy; 
      Division of Pathology, European Institute of Oncology, Milan, Italy; University 
      of Milan School of Medicine, Milan, Italy.
FAU - Verdun di Cantogno, Ludovica
AU  - Verdun di Cantogno L
AD  - Department of Medical Sciences, University of Turin, Turin, Italy; Pathology 
      Unit, Department of Laboratory Medicine, Azienda Ospedaliera Citta della Salute e 
      della Scienza di Torino, Turin, Italy; Pathology Division, Santa Croce Hospital, 
      Moncalieri, Italy; Pathology Division, Azienda USL Valle d'Aosta, Aosta, Italy; 
      Pathology Division, Valdese Hospital, Turin, Italy; Pathology Division, Martini 
      Hospital, Turin, Italy; Pathology Division, ASL 9, Civile Hospital, Ivrea, Italy; 
      Department of Pathology, Regina Elena National Cancer Institute, Rome, Italy; 
      Division of Pathology, European Institute of Oncology, Milan, Italy; University 
      of Milan School of Medicine, Milan, Italy.
FAU - Macri, Luigia
AU  - Macri L
AD  - Department of Medical Sciences, University of Turin, Turin, Italy; Pathology 
      Unit, Department of Laboratory Medicine, Azienda Ospedaliera Citta della Salute e 
      della Scienza di Torino, Turin, Italy; Pathology Division, Santa Croce Hospital, 
      Moncalieri, Italy; Pathology Division, Azienda USL Valle d'Aosta, Aosta, Italy; 
      Pathology Division, Valdese Hospital, Turin, Italy; Pathology Division, Martini 
      Hospital, Turin, Italy; Pathology Division, ASL 9, Civile Hospital, Ivrea, Italy; 
      Department of Pathology, Regina Elena National Cancer Institute, Rome, Italy; 
      Division of Pathology, European Institute of Oncology, Milan, Italy; University 
      of Milan School of Medicine, Milan, Italy.
FAU - Botta, Cristina
AU  - Botta C
AD  - Department of Medical Sciences, University of Turin, Turin, Italy; Pathology 
      Unit, Department of Laboratory Medicine, Azienda Ospedaliera Citta della Salute e 
      della Scienza di Torino, Turin, Italy; Pathology Division, Santa Croce Hospital, 
      Moncalieri, Italy; Pathology Division, Azienda USL Valle d'Aosta, Aosta, Italy; 
      Pathology Division, Valdese Hospital, Turin, Italy; Pathology Division, Martini 
      Hospital, Turin, Italy; Pathology Division, ASL 9, Civile Hospital, Ivrea, Italy; 
      Department of Pathology, Regina Elena National Cancer Institute, Rome, Italy; 
      Division of Pathology, European Institute of Oncology, Milan, Italy; University 
      of Milan School of Medicine, Milan, Italy.
FAU - Gugliotta, Patrizia
AU  - Gugliotta P
AD  - Department of Medical Sciences, University of Turin, Turin, Italy; Pathology 
      Unit, Department of Laboratory Medicine, Azienda Ospedaliera Citta della Salute e 
      della Scienza di Torino, Turin, Italy; Pathology Division, Santa Croce Hospital, 
      Moncalieri, Italy; Pathology Division, Azienda USL Valle d'Aosta, Aosta, Italy; 
      Pathology Division, Valdese Hospital, Turin, Italy; Pathology Division, Martini 
      Hospital, Turin, Italy; Pathology Division, ASL 9, Civile Hospital, Ivrea, Italy; 
      Department of Pathology, Regina Elena National Cancer Institute, Rome, Italy; 
      Division of Pathology, European Institute of Oncology, Milan, Italy; University 
      of Milan School of Medicine, Milan, Italy.
FAU - Scalzo, Maria Stella
AU  - Scalzo MS
AD  - Department of Medical Sciences, University of Turin, Turin, Italy; Pathology 
      Unit, Department of Laboratory Medicine, Azienda Ospedaliera Citta della Salute e 
      della Scienza di Torino, Turin, Italy; Pathology Division, Santa Croce Hospital, 
      Moncalieri, Italy; Pathology Division, Azienda USL Valle d'Aosta, Aosta, Italy; 
      Pathology Division, Valdese Hospital, Turin, Italy; Pathology Division, Martini 
      Hospital, Turin, Italy; Pathology Division, ASL 9, Civile Hospital, Ivrea, Italy; 
      Department of Pathology, Regina Elena National Cancer Institute, Rome, Italy; 
      Division of Pathology, European Institute of Oncology, Milan, Italy; University 
      of Milan School of Medicine, Milan, Italy.
FAU - Annaratone, Laura
AU  - Annaratone L
AD  - Department of Medical Sciences, University of Turin, Turin, Italy; Pathology 
      Unit, Department of Laboratory Medicine, Azienda Ospedaliera Citta della Salute e 
      della Scienza di Torino, Turin, Italy; Pathology Division, Santa Croce Hospital, 
      Moncalieri, Italy; Pathology Division, Azienda USL Valle d'Aosta, Aosta, Italy; 
      Pathology Division, Valdese Hospital, Turin, Italy; Pathology Division, Martini 
      Hospital, Turin, Italy; Pathology Division, ASL 9, Civile Hospital, Ivrea, Italy; 
      Department of Pathology, Regina Elena National Cancer Institute, Rome, Italy; 
      Division of Pathology, European Institute of Oncology, Milan, Italy; University 
      of Milan School of Medicine, Milan, Italy.
FAU - Balmativola, Davide
AU  - Balmativola D
AD  - Department of Medical Sciences, University of Turin, Turin, Italy; Pathology 
      Unit, Department of Laboratory Medicine, Azienda Ospedaliera Citta della Salute e 
      della Scienza di Torino, Turin, Italy; Pathology Division, Santa Croce Hospital, 
      Moncalieri, Italy; Pathology Division, Azienda USL Valle d'Aosta, Aosta, Italy; 
      Pathology Division, Valdese Hospital, Turin, Italy; Pathology Division, Martini 
      Hospital, Turin, Italy; Pathology Division, ASL 9, Civile Hospital, Ivrea, Italy; 
      Department of Pathology, Regina Elena National Cancer Institute, Rome, Italy; 
      Division of Pathology, European Institute of Oncology, Milan, Italy; University 
      of Milan School of Medicine, Milan, Italy.
FAU - Pietribiasi, Francesca
AU  - Pietribiasi F
AD  - Department of Medical Sciences, University of Turin, Turin, Italy; Pathology 
      Unit, Department of Laboratory Medicine, Azienda Ospedaliera Citta della Salute e 
      della Scienza di Torino, Turin, Italy; Pathology Division, Santa Croce Hospital, 
      Moncalieri, Italy; Pathology Division, Azienda USL Valle d'Aosta, Aosta, Italy; 
      Pathology Division, Valdese Hospital, Turin, Italy; Pathology Division, Martini 
      Hospital, Turin, Italy; Pathology Division, ASL 9, Civile Hospital, Ivrea, Italy; 
      Department of Pathology, Regina Elena National Cancer Institute, Rome, Italy; 
      Division of Pathology, European Institute of Oncology, Milan, Italy; University 
      of Milan School of Medicine, Milan, Italy.
FAU - Bernardi, Paolo
AU  - Bernardi P
AD  - Department of Medical Sciences, University of Turin, Turin, Italy; Pathology 
      Unit, Department of Laboratory Medicine, Azienda Ospedaliera Citta della Salute e 
      della Scienza di Torino, Turin, Italy; Pathology Division, Santa Croce Hospital, 
      Moncalieri, Italy; Pathology Division, Azienda USL Valle d'Aosta, Aosta, Italy; 
      Pathology Division, Valdese Hospital, Turin, Italy; Pathology Division, Martini 
      Hospital, Turin, Italy; Pathology Division, ASL 9, Civile Hospital, Ivrea, Italy; 
      Department of Pathology, Regina Elena National Cancer Institute, Rome, Italy; 
      Division of Pathology, European Institute of Oncology, Milan, Italy; University 
      of Milan School of Medicine, Milan, Italy.
FAU - Arisio, Riccardo
AU  - Arisio R
AD  - Department of Medical Sciences, University of Turin, Turin, Italy; Pathology 
      Unit, Department of Laboratory Medicine, Azienda Ospedaliera Citta della Salute e 
      della Scienza di Torino, Turin, Italy; Pathology Division, Santa Croce Hospital, 
      Moncalieri, Italy; Pathology Division, Azienda USL Valle d'Aosta, Aosta, Italy; 
      Pathology Division, Valdese Hospital, Turin, Italy; Pathology Division, Martini 
      Hospital, Turin, Italy; Pathology Division, ASL 9, Civile Hospital, Ivrea, Italy; 
      Department of Pathology, Regina Elena National Cancer Institute, Rome, Italy; 
      Division of Pathology, European Institute of Oncology, Milan, Italy; University 
      of Milan School of Medicine, Milan, Italy.
FAU - Viberti, Laura
AU  - Viberti L
AD  - Department of Medical Sciences, University of Turin, Turin, Italy; Pathology 
      Unit, Department of Laboratory Medicine, Azienda Ospedaliera Citta della Salute e 
      della Scienza di Torino, Turin, Italy; Pathology Division, Santa Croce Hospital, 
      Moncalieri, Italy; Pathology Division, Azienda USL Valle d'Aosta, Aosta, Italy; 
      Pathology Division, Valdese Hospital, Turin, Italy; Pathology Division, Martini 
      Hospital, Turin, Italy; Pathology Division, ASL 9, Civile Hospital, Ivrea, Italy; 
      Department of Pathology, Regina Elena National Cancer Institute, Rome, Italy; 
      Division of Pathology, European Institute of Oncology, Milan, Italy; University 
      of Milan School of Medicine, Milan, Italy.
FAU - Guzzetti, Stefano
AU  - Guzzetti S
AD  - Department of Medical Sciences, University of Turin, Turin, Italy; Pathology 
      Unit, Department of Laboratory Medicine, Azienda Ospedaliera Citta della Salute e 
      della Scienza di Torino, Turin, Italy; Pathology Division, Santa Croce Hospital, 
      Moncalieri, Italy; Pathology Division, Azienda USL Valle d'Aosta, Aosta, Italy; 
      Pathology Division, Valdese Hospital, Turin, Italy; Pathology Division, Martini 
      Hospital, Turin, Italy; Pathology Division, ASL 9, Civile Hospital, Ivrea, Italy; 
      Department of Pathology, Regina Elena National Cancer Institute, Rome, Italy; 
      Division of Pathology, European Institute of Oncology, Milan, Italy; University 
      of Milan School of Medicine, Milan, Italy.
FAU - Orlassino, Renzo
AU  - Orlassino R
AD  - Department of Medical Sciences, University of Turin, Turin, Italy; Pathology 
      Unit, Department of Laboratory Medicine, Azienda Ospedaliera Citta della Salute e 
      della Scienza di Torino, Turin, Italy; Pathology Division, Santa Croce Hospital, 
      Moncalieri, Italy; Pathology Division, Azienda USL Valle d'Aosta, Aosta, Italy; 
      Pathology Division, Valdese Hospital, Turin, Italy; Pathology Division, Martini 
      Hospital, Turin, Italy; Pathology Division, ASL 9, Civile Hospital, Ivrea, Italy; 
      Department of Pathology, Regina Elena National Cancer Institute, Rome, Italy; 
      Division of Pathology, European Institute of Oncology, Milan, Italy; University 
      of Milan School of Medicine, Milan, Italy.
FAU - Ercolani, Cristiana
AU  - Ercolani C
AD  - Department of Medical Sciences, University of Turin, Turin, Italy; Pathology 
      Unit, Department of Laboratory Medicine, Azienda Ospedaliera Citta della Salute e 
      della Scienza di Torino, Turin, Italy; Pathology Division, Santa Croce Hospital, 
      Moncalieri, Italy; Pathology Division, Azienda USL Valle d'Aosta, Aosta, Italy; 
      Pathology Division, Valdese Hospital, Turin, Italy; Pathology Division, Martini 
      Hospital, Turin, Italy; Pathology Division, ASL 9, Civile Hospital, Ivrea, Italy; 
      Department of Pathology, Regina Elena National Cancer Institute, Rome, Italy; 
      Division of Pathology, European Institute of Oncology, Milan, Italy; University 
      of Milan School of Medicine, Milan, Italy.
FAU - Mottolese, Marcella
AU  - Mottolese M
AD  - Department of Medical Sciences, University of Turin, Turin, Italy; Pathology 
      Unit, Department of Laboratory Medicine, Azienda Ospedaliera Citta della Salute e 
      della Scienza di Torino, Turin, Italy; Pathology Division, Santa Croce Hospital, 
      Moncalieri, Italy; Pathology Division, Azienda USL Valle d'Aosta, Aosta, Italy; 
      Pathology Division, Valdese Hospital, Turin, Italy; Pathology Division, Martini 
      Hospital, Turin, Italy; Pathology Division, ASL 9, Civile Hospital, Ivrea, Italy; 
      Department of Pathology, Regina Elena National Cancer Institute, Rome, Italy; 
      Division of Pathology, European Institute of Oncology, Milan, Italy; University 
      of Milan School of Medicine, Milan, Italy.
FAU - Viale, Giuseppe
AU  - Viale G
AD  - Department of Medical Sciences, University of Turin, Turin, Italy; Pathology 
      Unit, Department of Laboratory Medicine, Azienda Ospedaliera Citta della Salute e 
      della Scienza di Torino, Turin, Italy; Pathology Division, Santa Croce Hospital, 
      Moncalieri, Italy; Pathology Division, Azienda USL Valle d'Aosta, Aosta, Italy; 
      Pathology Division, Valdese Hospital, Turin, Italy; Pathology Division, Martini 
      Hospital, Turin, Italy; Pathology Division, ASL 9, Civile Hospital, Ivrea, Italy; 
      Department of Pathology, Regina Elena National Cancer Institute, Rome, Italy; 
      Division of Pathology, European Institute of Oncology, Milan, Italy; University 
      of Milan School of Medicine, Milan, Italy.
FAU - Marchio, Caterina
AU  - Marchio C
AD  - Department of Medical Sciences, University of Turin, Turin, Italy; Pathology 
      Unit, Department of Laboratory Medicine, Azienda Ospedaliera Citta della Salute e 
      della Scienza di Torino, Turin, Italy; Pathology Division, Santa Croce Hospital, 
      Moncalieri, Italy; Pathology Division, Azienda USL Valle d'Aosta, Aosta, Italy; 
      Pathology Division, Valdese Hospital, Turin, Italy; Pathology Division, Martini 
      Hospital, Turin, Italy; Pathology Division, ASL 9, Civile Hospital, Ivrea, Italy; 
      Department of Pathology, Regina Elena National Cancer Institute, Rome, Italy; 
      Division of Pathology, European Institute of Oncology, Milan, Italy; University 
      of Milan School of Medicine, Milan, Italy caterina.marchio@unito.it 
      anna.sapino@unito.it.
LA  - eng
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20141016
PL  - England
TA  - Oncologist
JT  - The oncologist
JID - 9607837
RN  - 0 (Autoantigens)
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (CEP250 protein, human)
RN  - EC 2.7.10.1 (ERBB2 protein, human)
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
SB  - IM
MH  - Autoantigens/genetics
MH  - Biomarkers, Tumor/genetics
MH  - Breast Neoplasms/*genetics/metabolism/pathology
MH  - Cell Cycle Proteins/genetics
MH  - Cohort Studies
MH  - Female
MH  - Gene Amplification
MH  - Gene Dosage
MH  - Guidelines as Topic
MH  - Humans
MH  - Immunohistochemistry
MH  - In Situ Hybridization, Fluorescence
MH  - Polymerase Chain Reaction/*methods
MH  - Receptor, ErbB-2/*genetics/metabolism
PMC - PMC4221371
OTO - NOTNLM
OT  - Breast cancer
OT  - Equivocal HER2 status
OT  - Guidelines
OT  - HER2 amplification
OT  - Heterogeneity
COIS- Disclosures of potential conflicts of interest may be found at the end of this 
      article.
EDAT- 2014/10/18 06:00
MHDA- 2015/07/28 06:00
PMCR- 2015/11/01
CRDT- 2014/10/18 06:00
PHST- 2014/10/18 06:00 [entrez]
PHST- 2014/10/18 06:00 [pubmed]
PHST- 2015/07/28 06:00 [medline]
PHST- 2015/11/01 00:00 [pmc-release]
AID - theoncologist.2014-0195 [pii]
AID - T14195 [pii]
AID - 10.1634/theoncologist.2014-0195 [doi]
PST - ppublish
SO  - Oncologist. 2014 Nov;19(11):1118-26. doi: 10.1634/theoncologist.2014-0195. Epub 
      2014 Oct 16.