PMID- 25527175
OWN - NLM
STAT- MEDLINE
DCOM- 20150521
LR  - 20201209
IS  - 1096-0945 (Electronic)
IS  - 0014-4800 (Linking)
VI  - 98
IP  - 1
DP  - 2015 Feb
TI  - Characterization of the 19q12 amplification including CCNE1 and URI in different 
      epithelial ovarian cancer subtypes.
PG  - 47-54
LID - S0014-4800(14)00201-9 [pii]
LID - 10.1016/j.yexmp.2014.12.004 [doi]
AB  - BACKGROUND: CCNE1 is frequently amplified in high grade serous ovarian cancer and 
      may serve as a target for ovarian cancer treatment. URI is closely related to 
      CCNE1 at the 19q12 amplicon and may also contribute to the oncogenic effect. Our 
      objective was to investigate the relevance of CCNE1 and URI gene amplification 
      and protein expression in different histological subtypes of epithelial ovarian 
      cancer (EOC). METHODS: A novel dual-color 19q12 in situ hybridization (ISH), 
      covering CCNE1 and URI, and chromosome 19 as a surrogate using Ventana BenchMark 
      XT platform was developed and applied to 148 EOCs. URI and CCNE1 amplifications 
      were separately assessed by fluorescence in situ hybridization (FISH). 
      Immunohistochemistry using a Cyclin E1 and a novel URI monoclonal antibody was 
      performed. RESULTS: Amplification of 19q12 was found in 36.6%, CCNE1 in 21.7%, 
      URI in 9.9%, and both genes simultaneously in 9% of EOC cases. High Cyclin E1 and 
      URI protein expression were observed in 52.2% and 26.1%, respectively. 
      Amplification of 19q12 occurred in all EOC subtypes and was associated with 
      amplification and expression of CCNE1/Cyclin E1, URI, TP53 mutation, and advanced 
      stage. CONCLUSION: The novel 19q12 ISH probe reliably detects both CCNE1 and URI 
      amplifications as confirmed by FISH. The combination of 19q12 amplification with 
      Cyclin E1 and URI protein expression may help to select patients more likely to 
      benefit from CDK2 targeted therapies.
CI  - Copyright (c) 2014 Elsevier Inc. All rights reserved.
FAU - Noske, Aurelia
AU  - Noske A
AD  - Institute of Surgical Pathology, University Hospital Zurich, Schmelzbergstr. 12, 
      CH-8091 Zurich, Switzerland. Electronic address: aurelia.noske@usz.ch.
FAU - Henricksen, Leigh A
AU  - Henricksen LA
AD  - Ventana Medical Systems, Inc., 1910 East Innovation Park Drive, Tucson, AZ 85755, 
      USA.
FAU - LaFleur, Bonnie
AU  - LaFleur B
AD  - Ventana Medical Systems, Inc., 1910 East Innovation Park Drive, Tucson, AZ 85755, 
      USA.
FAU - Zimmermann, Anne-Katrin
AU  - Zimmermann AK
AD  - Institute of Surgical Pathology, University Hospital Zurich, Schmelzbergstr. 12, 
      CH-8091 Zurich, Switzerland.
FAU - Tubbs, Alisa
AU  - Tubbs A
AD  - Ventana Medical Systems, Inc., 1910 East Innovation Park Drive, Tucson, AZ 85755, 
      USA.
FAU - Singh, Shalini
AU  - Singh S
AD  - Ventana Medical Systems, Inc., 1910 East Innovation Park Drive, Tucson, AZ 85755, 
      USA.
FAU - Storz, Martina
AU  - Storz M
AD  - Institute of Surgical Pathology, University Hospital Zurich, Schmelzbergstr. 12, 
      CH-8091 Zurich, Switzerland.
FAU - Fink, Daniel
AU  - Fink D
AD  - Department of Gynecology, University Hospital Zurich, Frauenklinikstr. 10, 8091 
      Zurich, Switzerland.
FAU - Moch, Holger
AU  - Moch H
AD  - Institute of Surgical Pathology, University Hospital Zurich, Schmelzbergstr. 12, 
      CH-8091 Zurich, Switzerland.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20141216
PL  - Netherlands
TA  - Exp Mol Pathol
JT  - Experimental and molecular pathology
JID - 0370711
RN  - 0 (CCNE1 protein, human)
RN  - 0 (Cyclin E)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Oncogene Proteins)
RN  - 0 (Repressor Proteins)
RN  - 0 (URI1 protein, human)
RN  - EC 2.7.11.22 (CDK2 protein, human)
RN  - EC 2.7.11.22 (Cyclin-Dependent Kinase 2)
SB  - IM
MH  - Adenocarcinoma, Clear Cell/genetics/metabolism/pathology
MH  - Adenocarcinoma, Mucinous/genetics/metabolism/pathology
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Chromosomes, Human, Pair 19/*genetics
MH  - Cyclin E/*genetics
MH  - Cyclin-Dependent Kinase 2/genetics
MH  - Cystadenocarcinoma, Serous/genetics/metabolism/pathology
MH  - Endometrial Neoplasms/genetics/metabolism/pathology
MH  - Female
MH  - Gene Amplification
MH  - Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - Immunoenzyme Techniques
MH  - In Situ Hybridization, Fluorescence
MH  - Intracellular Signaling Peptides and Proteins/*genetics
MH  - Middle Aged
MH  - Neoplasm Grading
MH  - Neoplasm Staging
MH  - Oncogene Proteins/*genetics
MH  - Ovarian Neoplasms/*genetics/metabolism/pathology
MH  - Prognosis
MH  - Repressor Proteins
OTO - NOTNLM
OT  - 19q12
OT  - CCNE1
OT  - Cyclin E1
OT  - Epithelial ovarian cancer
OT  - ISH
OT  - URI
EDAT- 2014/12/21 06:00
MHDA- 2015/05/23 06:00
CRDT- 2014/12/21 06:00
PHST- 2014/12/09 00:00 [received]
PHST- 2014/12/15 00:00 [accepted]
PHST- 2014/12/21 06:00 [entrez]
PHST- 2014/12/21 06:00 [pubmed]
PHST- 2015/05/23 06:00 [medline]
AID - S0014-4800(14)00201-9 [pii]
AID - 10.1016/j.yexmp.2014.12.004 [doi]
PST - ppublish
SO  - Exp Mol Pathol. 2015 Feb;98(1):47-54. doi: 10.1016/j.yexmp.2014.12.004. Epub 2014 
      Dec 16.