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
YO10 - Rectal Follicular Dendritic Cell Sarcoma
Presenter: Kripa Bajaj
Session: Poster display session
Resources:
Abstract
YO11 - Postoperative metastasis prediction based on portal vein circulating tumor cells detected by flow cytometry in periampullary or pancreatic cancer
Presenter: Lianyuan Tao
Session: Poster display session
Resources:
Abstract
YO12 - Case report of Hepatic EBV-associated smooth muscle tumor in AIDS patient
Presenter: Gorawich Kerkarchachai
Session: Poster display session
Resources:
Abstract
YO13 - IgG4-related pseudo-tumor of the kidney and multiple organ involvement mimicked malignancy
Presenter: Wasamol Mahaparn
Session: Poster display session
Resources:
Abstract
YO14 - Urachal Adenocarcinoma: Case Report
Presenter: Michelle Joane Alcantara
Session: Poster display session
Resources:
Abstract
YO15 - Concurrent Atezolizumab-Radiotherapy in Locally Recurrent Urinary Bladder Carcinoma: A Case Report
Presenter: Ma. Angelle Lalaine Dantes
Session: Poster display session
Resources:
Abstract
YO16 - Clear cell RCC with synchronous metastasis at transplanted kidney and bone in patient post Cadaveric donor kidney transplantation
Presenter: Punyaporn Cheewasathianchai
Session: Poster display session
Resources:
Abstract
YO17 - Serous ovarian cancer treated with palbociclib and letrozole
Presenter: Dai Wee Lee
Session: Poster display session
Resources:
Abstract
YO18 - A patient with Peutz-Jegher syndrome who incidentally found sex cord stromal tumor: a case report
Presenter: Pongput Pimsa
Session: Poster display session
Resources:
Abstract
YO19 - A case of CLL/SLL with transdifferentiation to dendritic cell tumor and possibly a hybrid lymphodendritic cell neoplasm:The missing link?
Presenter: Yanping Chen
Session: Poster display session
Resources:
Abstract