PMID- 25720673
OWN - NLM
STAT- MEDLINE
DCOM- 20160229
LR  - 20181113
IS  - 2045-7634 (Electronic)
IS  - 2045-7634 (Print)
IS  - 2045-7634 (Linking)
VI  - 4
IP  - 6
DP  - 2015 Jun
TI  - HER2 as a target in invasive urothelial carcinoma.
PG  - 844-52
LID - 10.1002/cam4.432 [doi]
AB  - We evaluated primary tumors from two cohorts, Spain (N = 111) and Greece (N = 
      102), for patients who were treated with platinum-based chemotherapy. Patients 
      were tested for HER2 status (IHC score of 3+ or FISH ratio of >/= 2.2) by 
      immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), DNA copy 
      number, mRNA expression, and mutation status in patients with metastatic 
      urothelial carcinoma (UC), and its impact on survival. ERBB2 mutation was 
      determined by hotspot sequencing. mRNA expression was assessed using NanoString 
      counting. Association of overall survival (OS) and HER2 status was assessed by a 
      Cox regression model. NIH-3T3 cells containing HER2 V777L were assessed for 
      growth, invasion, and HER2 kinase activation. In all, 22% of Spanish and 4% of 
      Greek cohorts had 3+ HER2 staining by IHC. FISH amplification was identified in 
      20% of Spanish and 4% of Greek cohorts. Kappa coefficient between FISH and IHC 
      was 0.47. HER2 status was not associated with OS in univariate (Spanish P = 0.34; 
      Greek P = 0.11) or multivariate (Spanish P = 0.49; Greek P = 0.12) analysis. 
      HER2-positive tumors expressed higher levels of HER2 mRNA than HER2-negative 
      tumors (P < 0.001). HER2 mutations (V777L and L755S) were identified in two (2%) 
      patients. In vitro analysis of V777L results in transformation of NIH-3T3 cells, 
      leading to increased growth, invasion on soft agar, and HER2 kinase constitutive 
      activation. In summary, HER2 overexpression or amplification in the primary tumor 
      did not predict OS in patients with metastatic UC. HER2 positivity rates can 
      differ between different populations. Further trials in genomically screened 
      patients are needed to assess HER2-targeted therapies in UC.
CI  - (c) 2015 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.
FAU - Bellmunt, Joaquim
AU  - Bellmunt J
AD  - Bladder Cancer Center, Lank Center for Genitourinary Oncology, Dana-Farber Cancer 
      Institute, Boston, Massachusetts.
AD  - Department of Medical Oncology, University Hospital de Mar-IMIM, Barcelona, 
      Spain.
FAU - Werner, Lillian
AU  - Werner L
AD  - Department of Biostatistics and Computational Biology, Dana-Farber Cancer 
      Institute, Boston, Massachusetts.
FAU - Bamias, Aristotle
AU  - Bamias A
AD  - University of Athens and Hellenic Co-operative Oncology Group, Athens, Greece.
FAU - Fay, Andre P
AU  - Fay AP
AD  - Bladder Cancer Center, Lank Center for Genitourinary Oncology, Dana-Farber Cancer 
      Institute, Boston, Massachusetts.
FAU - Park, Rachel S
AU  - Park RS
AD  - Bladder Cancer Center, Lank Center for Genitourinary Oncology, Dana-Farber Cancer 
      Institute, Boston, Massachusetts.
FAU - Riester, Markus
AU  - Riester M
AD  - Department of Biostatistics and Computational Biology, Dana-Farber Cancer 
      Institute, Boston, Massachusetts.
FAU - Selvarajah, Shamini
AU  - Selvarajah S
AD  - Center for Molecular Oncologic Pathology, Department of Pathology, Brigham and 
      Women's Hospital, Boston, Massachusetts.
FAU - Barletta, Justine A
AU  - Barletta JA
AD  - Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts.
FAU - Berman, David M
AU  - Berman DM
AD  - The Johns Hopkins University School of Medicine, Baltimore, Maryland.
FAU - de Muga, Silvia
AU  - de Muga S
AD  - Hospital de Mar Research Institute-IMIM, Barcelona, Spain.
FAU - Salido, Marta
AU  - Salido M
AD  - Hospital de Mar Research Institute-IMIM, Barcelona, Spain.
FAU - Gallardo, Enrique
AU  - Gallardo E
AD  - Hospital Parc Tauli, Sabadell, Spain.
FAU - Rojo, Federico
AU  - Rojo F
AD  - Hospital de Mar Research Institute-IMIM, Barcelona, Spain.
AD  - IIS-Fundacion Jimenez Diaz, Madrid, Spain.
FAU - Guancial, Elizabeth A
AU  - Guancial EA
AUID- ORCID: 0000-0002-6518-5179
AD  - Bladder Cancer Center, Lank Center for Genitourinary Oncology, Dana-Farber Cancer 
      Institute, Boston, Massachusetts.
FAU - Bambury, Richard
AU  - Bambury R
AD  - Memorial Sloan Kettering Cancer Center, New York City, New York.
FAU - Mullane, Stephanie A
AU  - Mullane SA
AD  - Bladder Cancer Center, Lank Center for Genitourinary Oncology, Dana-Farber Cancer 
      Institute, Boston, Massachusetts.
FAU - Choueiri, Toni K
AU  - Choueiri TK
AD  - Bladder Cancer Center, Lank Center for Genitourinary Oncology, Dana-Farber Cancer 
      Institute, Boston, Massachusetts.
FAU - Loda, Massimo
AU  - Loda M
AD  - Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts.
FAU - Stack, Edward
AU  - Stack E
AD  - Center for Molecular Oncologic Pathology, Department of Pathology, Brigham and 
      Women's Hospital, Boston, Massachusetts.
FAU - Rosenberg, Jonathan
AU  - Rosenberg J
AD  - Bladder Cancer Center, Lank Center for Genitourinary Oncology, Dana-Farber Cancer 
      Institute, Boston, Massachusetts.
AD  - Memorial Sloan Kettering Cancer Center, New York City, New York.
LA  - eng
SI  - ClinicalTrials.gov/NCT00949455
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20150226
PL  - United States
TA  - Cancer Med
JT  - Cancer medicine
JID - 101595310
RN  - 0 (RNA, Messenger)
RN  - EC 2.7.10.1 (ERBB2 protein, human)
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
SB  - IM
CIN - J Urol. 2016 Dec;196(6):1637-1639. PMID: 27845103
MH  - Clinical Trials, Phase III as Topic
MH  - Cohort Studies
MH  - DNA Copy Number Variations/genetics
MH  - Humans
MH  - Immunohistochemistry
MH  - In Situ Hybridization, Fluorescence
MH  - Mutation/*genetics
MH  - Neoplasm Metastasis
MH  - Observer Variation
MH  - RNA, Messenger/genetics/metabolism
MH  - Receptor, ErbB-2/genetics/*metabolism
MH  - Survival Analysis
MH  - Urinary Bladder Neoplasms/drug therapy/*genetics
PMC - PMC4472207
OTO - NOTNLM
OT  - ERBB2
OT  - HER2
OT  - genomic alterations
OT  - prognosis
OT  - urothelial carcinomas
EDAT- 2015/02/28 06:00
MHDA- 2016/03/02 06:00
PMCR- 2015/06/01
CRDT- 2015/02/28 06:00
PHST- 2014/09/03 00:00 [received]
PHST- 2015/01/12 00:00 [revised]
PHST- 2015/01/13 00:00 [accepted]
PHST- 2015/02/28 06:00 [entrez]
PHST- 2015/02/28 06:00 [pubmed]
PHST- 2016/03/02 06:00 [medline]
PHST- 2015/06/01 00:00 [pmc-release]
AID - 10.1002/cam4.432 [doi]
PST - ppublish
SO  - Cancer Med. 2015 Jun;4(6):844-52. doi: 10.1002/cam4.432. Epub 2015 Feb 26.