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.

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.

Citation

Abdel-Fatah, T. M., Rees, R. C., Pockley, A. G., Moseley, P., Ball, G. R., Chan, S. Y., Ellis, I. O., & Miles, A. K. (2017). 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. Oncotarget, 8(68), 112245-112257. https://doi.org/10.18632/oncotarget.22496

• 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
• Contract Date: Aug 8, 2019