title: Characterization of the 19q12 amplification including CCNE1 and URI in different epithelial ovarian cancer subtypes.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Institute of Surgical Pathology, University Hospital Zurich, Schmelzbergstr. 12, CH-8091 Zurich, Switzerland. Electronic address: aurelia.noske@usz.ch.
authors.forename: Aurelia
authors.initials: A
authors.lastname: Noske
authors.affiliation: Ventana Medical Systems, Inc., 1910 East Innovation Park Drive, Tucson, AZ 85755, USA.
authors.forename: Leigh A
authors.initials: LA
authors.lastname: Henricksen
authors.affiliation: Ventana Medical Systems, Inc., 1910 East Innovation Park Drive, Tucson, AZ 85755, USA.
authors.forename: Bonnie
authors.initials: B
authors.lastname: LaFleur
authors.affiliation: Institute of Surgical Pathology, University Hospital Zurich, Schmelzbergstr. 12, CH-8091 Zurich, Switzerland.
authors.forename: Anne-Katrin
authors.initials: AK
authors.lastname: Zimmermann
authors.affiliation: Ventana Medical Systems, Inc., 1910 East Innovation Park Drive, Tucson, AZ 85755, USA.
authors.forename: Alisa
authors.initials: A
authors.lastname: Tubbs
authors.affiliation: Ventana Medical Systems, Inc., 1910 East Innovation Park Drive, Tucson, AZ 85755, USA.
authors.forename: Shalini
authors.initials: S
authors.lastname: Singh
authors.affiliation: Institute of Surgical Pathology, University Hospital Zurich, Schmelzbergstr. 12, CH-8091 Zurich, Switzerland.
authors.forename: Martina
authors.initials: M
authors.lastname: Storz
authors.affiliation: Department of Gynecology, University Hospital Zurich, Frauenklinikstr. 10, 8091 Zurich, Switzerland.
authors.forename: Daniel
authors.initials: D
authors.lastname: Fink
authors.affiliation: Institute of Surgical Pathology, University Hospital Zurich, Schmelzbergstr. 12, CH-8091 Zurich, Switzerland.
authors.forename: Holger
authors.initials: H
authors.lastname: Moch
mesh_terms: D018262:Adenocarcinoma, Clear Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002288:Adenocarcinoma, Mucinous / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics*; D019927:Cyclin E / Q000235:genetics*; D051357:Cyclin-Dependent Kinase 2 / Q000235:genetics; D018284:Cystadenocarcinoma, Serous / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D016889:Endometrial Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D005260:Female; D005784:Gene Amplification; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007124:Immunoenzyme Techniques; D017404:In Situ Hybridization, Fluorescence; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D015513:Oncogene Proteins / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D011379:Prognosis; D012097:Repressor Proteins
chemical_list: C475820:CCNE1 protein, human; D019927:Cyclin E; D047908:Intracellular Signaling Peptides and Proteins; D015513:Oncogene Proteins; D012097:Repressor Proteins; C117184:URI1 protein, human; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2
keywords: 19q12; CCNE1; Cyclin E1; Epithelial ovarian cancer; ISH; URI