title: Detection of CCNE1/URI (19q12) amplification by in situ hybridisation is common in high grade and type II endometrial cancer.
abstract: One TCGA subgroup of endometrial cancer (EC) is characterised by extensive genomic DNA copy number alterations. CCNE1 located at 19q12 is frequently amplified in EC and a target for anti-cancer therapy. The relevance of URI, also located at 19q12, is unknown. To evaluate the prevalence of 19q12 (CCNE1/URI) in EC, we investigated different histologic types by in situ hybridisation (ISH) and copy number assay. We applied a previously established 19q12 ISH for the detection of CCNE1/URI copy numbers in EC (n = 270) using conventional bright field microscopy. In a subset (n = 21), 19q12 amplification status was validated by OncoScan assay. Manual ISH was controlled by a recently developed computational ISHProfiler algorithm. Associations of 19q12 status with Cyclin E1, URI and p53 expression, and clinico-pathological parameters were tested.Amplification of 19q12 (CCNE1/URI) was found in 10.4% (28/270) and was significantly associated with type II EC (high grade and non-endometrioid; p < 0.0001), advanced FIGO stage (p = 0.001), high Cyclin E1 expression (p = 0.008) and aberrant p53 expression (p = 0.04). 19q12 ISH data were confirmed by OncoScan and computational ISHProfiler techniques. The 19q12 in situ hybridisation is a feasible and robust biomarker assay in molecular pathology. Amplification of CCNE1/URI predominantly occurred in type II endometrial cancer. Prospective clinical trials are warranted to assess the utility of combined 19q12 amplification and Cyclin E1/URI protein expression analysis for the prediction of therapeutic response to chemotherapy and/or cyclin-dependent kinase inhibitors in patients with endometrial cancer.
authors: Institute of Surgical Pathology, University Hospital Zurich, Zurich, Switzerland.
authors: Aurelia
authors: A
authors: Noske
authors: Institute of Surgical Pathology, University Hospital Zurich, Zurich, Switzerland.
authors: Simone
authors: S
authors: Brandt
authors: Institute of Surgical Pathology, University Hospital Zurich, Zurich, Switzerland.
authors: Nadejda
authors: N
authors: Valtcheva
authors: Institute of Surgical Pathology, University Hospital Zurich, Zurich, Switzerland.
authors: Ulrich
authors: U
authors: Wagner
authors: Institute of Surgical Pathology, University Hospital Zurich, Zurich, Switzerland.
authors: Qing
authors: Q
authors: Zhong
authors: Institute of Surgical Pathology, University Hospital Zurich, Zurich, Switzerland.
authors: Elisa
authors: E
authors: Bellini
authors: Department of Gynaecology, University Hospital Zurich, Zurich, Switzerland.
authors: Daniel
authors: D
authors: Fink
authors: Institute of Pathology, University Hospital Basel, Basel, Switzerland.
authors: Ellen C
authors: EC
authors: Obermann
authors: Institute of Surgical Pathology, University Hospital Zurich, Zurich, Switzerland.
authors: Holger
authors: H
authors: Moch
authors: Institute of Surgical Pathology, University Hospital Zurich, Zurich, Switzerland.
authors: Peter J
authors: PJ
authors: Wild
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics*; D019295:Computational Biology / Q000379:methods; D019927:Cyclin E / Q000235:genetics* / Q000378:metabolism; D016889:Endometrial Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D005240:Feasibility Studies; D005260:Female; D005784:Gene Amplification; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization / Q000379:methods*; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism; D053208:Kaplan-Meier Estimate; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D015513:Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D017063:Outcome Assessment, Health Care; D012097:Repressor Proteins; D015203:Reproducibility of Results; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; C475820:CCNE1 protein, human; D019927:Cyclin E; D047908:Intracellular Signaling Peptides and Proteins; D015513:Oncogene Proteins; D012097:Repressor Proteins; D016159:Tumor Suppressor Protein p53; C117184:URI1 protein, human
keywords: 19q12; endometrial cancer; in situ hybridisation