Tarek M.A. Abdel-Fatah
The localization of pre mRNA splicing factor PRPF38B is a novel prognostic biomarker that may predict survival benefit of trastuzumab in patients with breast cancer overexpressing HER2
Abdel-Fatah, Tarek M.A.; Rees, Robert C.; Pockley, A. Graham; Moseley, Paul; Ball, Graham R.; Chan, Stephen Y.T.; Ellis, Ian O.; Miles, Amanda K.
Authors
Robert C. Rees
A. Graham Pockley
Paul Moseley
Graham R. Ball
Stephen Y.T. Chan
Professor IAN ELLIS IAN.ELLIS@NOTTINGHAM.AC.UK
Professor of Cancer Pathology
Amanda K. Miles
Abstract
Cancer biomarkers that can define disease status and provide a prognostic insight are essential for the effective management of patients with breast cancer (BC).
The prevalence, clinicopathological and prognostic significance of PRPF38B expression in a consecutive series of 1650 patients with primary invasive breast carcinoma were examined using immunohistochemistry. Furthermore, the relationship(s) between clinical outcome and PRPF38B expression was explored in 627 patients with ER-negative (oestrogen receptor) disease, and 322 patients with HER2-overexpressing disease.
Membranous expression of PRPF38B was observed in 148/1388 (10.7%) cases and was significantly associated with aggressive clinicopathological features, including high grade, high mitotic index, pleomorphism, invasive ductal carcinoma of no specific type (IDC-NST), ER-negative, HER2-overexpression and p53 mutational status (all p < 0.01). In patients with ER-negative disease receiving chemotherapy, nuclear expression of PRPF38B was significantly associated with a reduced risk of relapse (p = 0.0004), whereas membranous PRPF38B expression was significantly associated with increased risk of relapse (p = 0.004; respectively) at a 5 year follow-up. When patients were stratified according to ER-negative/HER2-positive status, membranous PRPF38B expression was associated with a higher risk of relapse in those patients that did not receive trastuzumab therapy (p = 0.02), whereas in those patients with ER-negative/HER2-positive disease that received trastuzumab adjuvant therapy, membranous PRPF38B expression associated with a lower risk of relapse (p = 0.00018).
Nuclear expression of PRPF38B is a good prognostic indicator in both ER-negative patients and ER-negative/HER2-positive BC (breast cancer) patients, whereas membranous localisation of PRPF38B is a poor prognostic biomarker that predicts survival benefit from trastuzumab therapy in patients with ER-negative/HER2-overexpressing BC.
Journal Article Type | Article |
---|---|
Acceptance Date | Oct 28, 2017 |
Online Publication Date | Nov 18, 2017 |
Publication Date | Nov 18, 2017 |
Deposit Date | Aug 8, 2019 |
Publicly Available Date | Aug 8, 2019 |
Journal | Oncotarget |
Electronic ISSN | 1949-2553 |
Publisher | Impact Journals |
Peer Reviewed | Peer Reviewed |
Volume | 8 |
Issue | 68 |
Pages | 112245-112257 |
DOI | https://doi.org/10.18632/oncotarget.22496 |
Public URL | https://nottingham-repository.worktribe.com/output/2407643 |
Publisher URL | http://www.oncotarget.com/index.php?journal=oncotarget&page=article&op=view&path[]=22496&path[]=71119 |
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The localization of pre mRNA splicing factor PRPF38B is a novel prognostic biomarker that may predict survival benefit of trastuzumab in patients with breast cancer overexpressing HER2
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