Abstract 254P
Background
HGSOC and BLBC are aggressive cancers that share aetiology, co-occur frequently and share molecular signatures including cyclin E1 deregulation. In HGSOC, we have described two cyclin E1 high groups, with and without associated gene amplification. We aimed to determine which subsets of these disease have the greatest similarity in terms of cyclin E1 as a biomarkers of response with the ultimate aim of groping similar subsets in the future for therapeutic purposes.
Methods
Using automated tissue based assays, we assessed the expression and the amplification status of cyclin E1 in a cohort enriched for familial cancer mutations against each of the expression of cyclin E1 degradation associated proteins, i.e., FBXW7 and USP28, BRCA status and clinical outcome and in comparison with cyclin E1 high subsets of HGSOC.
Results
For BLBC cyclin E1 overexpression but not CCNE1 amplification was found to be prognostic for overall survival. By comparison, both cyclin E1 expression and CCNE1 gene amplification are prognostic for HGSOC, which we establish with a meta-analysis of existing studies. We examined the nature of CCNE1 amplification to find that HGSOC has an enhanced degree of amplification of CCNE1 with 5.6x copies compared to 3.9x CCNE1 copies in BLBC, and this was associated with widely different expression of cyclin E1 protein. We find that BLBC cancers, with or without CCNE1 amplification, have similarities in dysregulation of regulators of cyclin E1 protein stability and those shared more features with the non-amplified cyclin E1 high HGSOC subset. Since cyclin E1 is only expressed at high levels in HGSOC and not BLBC, we examined the consequence of very high cyclin E1 expression in a BLBC cell line, MDA-MB-468. Moderate overexpression of cyclin E1 showed increased survival upon treatment with Paclitaxel, however very high expression of cyclin E1 gave less survival benefit.
Conclusions
We conclude that cyclin E1 high BLBC shared features with the non-amplified cyclin E1 high subset, high cyclin E1 expression associated with CCNE1 amplification gives rise to a unique phenotype in HGSOC, but otherwise the high expression of cyclin E1 protein may be a similar prognostic marker for BLBC and HGSOC.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Ventana Medical System.
D. Aziz: Research grant / Funding (self), provided reagents and technical support: Ventana Medical System. P.M. Waring: Research grant / Funding (institution), Full / Part-time employment, provided reagents and technical support, worked for about 10 months for ventana during the project: Ventana Medical System. All other authors have declared no conflicts of interest.
Resources from the same session
74TiP - Phase I study of BI 836880, a VEGF/Ang2-blocking nanobody®, as monotherapy and in combination with BI 754091, an anti-PD-1 antibody, in Japanese patients (pts) with advanced solid tumours
Presenter: Kentaro Yamazaki
Session: Poster display session
Resources:
Abstract
75P - A parallel deep learning network framework for whole-body bone scan image analysis
Presenter: Xiaorong Pu
Session: Poster display session
Resources:
Abstract
76P - Perception and satisfaction of cancer patients in clinical trials
Presenter: Jukyung Jeon
Session: Poster display session
Resources:
Abstract
77P - A prognostic nomogram for the prediction of neuroblastoma
Presenter: Jian-Guo Zhou
Session: Poster display session
Resources:
Abstract
80P - The clinical usefulness of a new fat-dissociation method to detect lymph nodes from surgically resected specimen in colorectal cancer: Prospective randomized study
Presenter: Shiki Fujino
Session: Poster display session
Resources:
Abstract
81P - Concurrent or consolidation chemotherapy during radiation as neoadjuvant treatment for locally advanced rectal cancer: A propensity score analysis from two prospective study
Presenter: JianWei Zhang
Session: Poster display session
Resources:
Abstract
82P - Body mass index, tumour location, and colorectal cancer survival
Presenter: Dake Chu
Session: Poster display session
Resources:
Abstract
83P - Helicobacter bilis may play a role in the carcinogenesis of colitis associated colon cancer correlating to increased number of CD4+CD45RB+ T cells
Presenter: Xiangsheng Fu
Session: Poster display session
Resources:
Abstract
84P - Comprehensive evaluation of relapse risk (CERR) score for colorectal liver metastases development and validation
Presenter: Jianmin Xu
Session: Poster display session
Resources:
Abstract
85P - Which is the best partner for capecitabine-based neoadjuvant chemoradiotherapy in locally advanced rectal cancer? A retrospective analysis of a comprehensive cancer center
Presenter: Jingwen Wang
Session: Poster display session
Resources:
Abstract