The localisation 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, T.M.A., Rees, R.C., Pockley, A.G. ORCID: 0000-0001-9593-6431, Moseley, P., Ball, G.R. ORCID: 0000-0001-5828-7129, Chan, S.Y.T., Ellis, I.O. and Miles, A.K. ORCID: 0000-0002-5388-938X, 2017. The localisation 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. Oncotarget. ISSN 1949-2553

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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.

Item Type: Journal article
Publication Title: Oncotarget
Creators: Abdel-Fatah, T.M.A., Rees, R.C., Pockley, A.G., Moseley, P., Ball, G.R., Chan, S.Y.T., Ellis, I.O. and Miles, A.K.
Publisher: Impact Journals
Date: 18 November 2017
ISSN: 1949-2553
Identifiers:
NumberType
10.18632/oncotarget.22496DOI
22496Publisher Item Identifier
Rights: This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0).
Divisions: Schools > School of Science and Technology
Depositing User: Jonathan Gallacher
Date Added: 07 Dec 2017 15:57
Last Modified: 07 Dec 2017 15:58
URI: http://irep.ntu.ac.uk/id/eprint/32168

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