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Detection of CCNE1/URI (19q12) amplification by in situ hybridisation is common in high grade and type II endometrial cancer

Noske, Aurelia; Brandt, Simone; Valtcheva, Nadejda; Wagner, Ulrich; Zhong, Qing; Bellini, Elisa; Fink, Daniel; Obermann, Ellen C; Moch, Holger; Wild, Peter J (2017). Detection of CCNE1/URI (19q12) amplification by in situ hybridisation is common in high grade and type II endometrial cancer. OncoTarget, 8(9):14794-14805.

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.

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Institute of Pathology and Molecular Pathology
04 Faculty of Medicine > University Hospital Zurich > Clinic for Gynecology
Dewey Decimal Classification:610 Medicine & health
Scopus Subject Areas:Health Sciences > Oncology
Language:English
Date:28 February 2017
Deposited On:29 Sep 2016 09:01
Last Modified:15 Oct 2024 01:41
Publisher:Impact Journals, LLC
ISSN:1949-2553
OA Status:Gold
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:https://doi.org/10.18632/oncotarget.11605
PubMed ID:27582547
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