Research Papers:

NHERF1 together with PARP1 and BRCA1 expression as a new potential biomarker to stratify breast cancer patients

Anita Mangia _, Emanuela Scarpi, Giulia Partipilo, Laura Schirosi, Giuseppina Opinto, Francesco Giotta and Giovanni Simone

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Oncotarget. 2017; 8:65730-65742. https://doi.org/10.18632/oncotarget.19444

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Anita Mangia1,*, Emanuela Scarpi2,*, Giulia Partipilo1, Laura Schirosi1, Giuseppina Opinto1, Francesco Giotta3 and Giovanni Simone4

1Functional Biomorphology Laboratory, IRCCS-Istituto Tumori “Giovanni Paolo II”, Bari 70124, Italy

2Unit of Biostatistics and Clinical Trials, (IRST)-IRCCS-Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, Meldola (FC) 47014, Italy

3Medical Oncology Unit, IRCCS-Istituto Tumori “Giovanni Paolo II”, Bari 70124, Italy

4Pathology Department, IRCCS-Istituto Tumori “Giovanni Paolo II”, Bari 70124, Italy

*These authors have contributed equally to this work

Correspondence to:

Anita Mangia, email: [email protected]

Keywords: Na+/H+ exchanger regulatory factor 1 (NHERF1), PARP1, BRCA1, breast cancer, immunohistochemistry

Received: December 22, 2016    Accepted: April 27, 2017    Published: July 22, 2017


It has been recognized that Na+/H+ Exchanger Regulatory Factor 1 (NHERF1) in breast cancer (BC) acts as a tumor suppressor or as an oncogenic protein, depending on its subcellular localization. This study aims to correlate NHERF1 expression to BRCA1 and PARP1 proteins, to investigate their relationship, and their biological and clinical significance. Using immunohistochemistry on tissue microarrays, we evaluated subcellular NHERF1, BRCA1 and PARP1 expression in 308 BCs including a subgroup (n=80) of triple negative BCs (TNBCs). Herein, we show that nuclear NHERF1 (nNHERF1) expression was significantly associated with nuclear BRCA1 (nBRCA1) expression (p=0.0008), and an association was also found between nuclear PARP1 (nPARP1) and nBRCA1 (p<0.0001). Cytoplasmic NHERF1 (cNHERF1) was correlated to nPARP1 (p<0.0001). Survival analyses showed that the patients with positive nPARP1 and nNHERF1 tended toward a shorter 5-year overall survival (OS) (p=0.057). In TNBCs, the association between nBRCA1 and nPARP1 was maintained (p<0.0001), and an association between nNHERF1 and nPARP1 was observed (p=0.010). Univariate analysis revealed that TNBCs with positive cNHERF1 and nPARP1 had a shorter 5-year OS (p=0.048).

Our data suggest that NHERF1 could be a new potential biomarker in combination with PARP1 and BRCA1 expression to stratify BC patients. In particular, in TNBCs, cNHERF1 associated with nPARP1 expression identified a patient subgroup with a shorter survival, for whom it may be useful to develop novel therapeutic strategies.

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