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

// Anita Mangia 1, * , Emanuela Scarpi 2, * , Giulia Partipilo 1 , Laura Schirosi 1 , Giuseppina Opinto 1 , Francesco Giotta 3 and Giovanni Simone 4 1 Functional Biomorphology Laboratory, IRCCS-Istituto Tumori “Giovanni Paolo II”, Bari 70124, Italy 2 Unit of Biostatistics and Clinical Trials, (IRST)-IRCCS-Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, Meldola (FC) 47014, Italy 3 Medical Oncology Unit, IRCCS-Istituto Tumori “Giovanni Paolo II”, Bari 70124, Italy 4 Pathology Department, IRCCS-Istituto Tumori “Giovanni Paolo II”, Bari 70124, Italy * These authors have contributed equally to this work Correspondence to: Anita Mangia, email: a.mangia@oncologico.bari.it 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 ABSTRACT 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.