Oncotarget

Research Papers:

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

Tarek M.A. Abdel-Fatah, Robert C. Rees, A. Graham Pockley, Paul Moseley, Graham R. Ball, Stephen Y.T. Chan, Ian O. Ellis and Amanda K. Miles _

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Oncotarget. 2017; 8:112245-112257. https://doi.org/10.18632/oncotarget.22496

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Abstract

Tarek M.A. Abdel-Fatah1, Robert C. Rees2, A. Graham Pockley2, Paul Moseley1, Graham R. Ball2, Stephen Y.T. Chan1, Ian O. Ellis3 and Amanda K. Miles2

1Department of Clinical Oncology, Nottingham City Hospital, Nottingham University Hospitals NHS Trust, Nottingham, NG5 1PB, UK

2The John van Geest Cancer Research Centre, Nottingham Trent University, Nottingham, NG11 8NS, UK

3Department of Histopathology, Nottingham City Hospital, Nottingham University Hospitals NHS Trust, Nottingham, NG5 1PB, UK

Correspondence to:

Amanda K. Miles, email: amanda.miles@ntu.ac.uk

Keywords: cancer antigen; PRPF38B; poor prognosis; ER-negative/HER2-positive breast cancer; trastuzumab therapy

Received: July 28, 2017     Accepted: October 28, 2017     Published: November 18, 2017

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.


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