Nuclear NHERF1 expression as a prognostic marker in breast cancer

• Published in: Cell death & disease 2013-11, Vol.4 (11), p.e904-e904
• Main Authors: Paradiso, A, Scarpi, E, Malfettone, A, Addati, T, Giotta, F, Simone, G, Amadori, D, Mangia, A
• Format: Article
• Language: English
• Subjects: 631/67/1347; 692/53/2422; Adult; Aged; Antibodies; Biochemistry; Biomedical and Life Sciences; Breast cancer; Breast Neoplasms - genetics; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Cell Biology; Cell Culture; Cell Nucleus - metabolism; Female; Humans; Immunohistochemistry; Immunology; In Vitro Techniques; Life Sciences; Male; Middle Aged; Original; original-article; Phosphoproteins - genetics; Phosphoproteins - metabolism; Prognosis; Sodium-Hydrogen Exchangers - genetics; Sodium-Hydrogen Exchangers - metabolism
• ISSN: 2041-4889; 2041-4889
• DOI: 10.1038/cddis.2013.439

Our purpose was to investigate whether Na + /H + exchanger regulatory factor 1 (NHERF1) expression could be linked to prognosis in invasive breast carcinomas. NHERF1, an ezrin-radixin-moesin (ERM) binding phosphoprotein 50, is involved in the linkage of integral membrane proteins to the cytoskeleton. It is therefore believed to have an important role in cell signaling associated with changes in cell cytoarchitecture. NHERF1 expression is observed in various types of cancer and is related to tumor aggressiveness. To date the most extensive analyses of the influence of NHERF1 in cancer development have been performed on breast cancer. However, the underlying mechanism and its prognostic significance are still undefined. NHERF1 expression was studied by immunohistochemistry (IHC) in a cohort of 222 breast carcinoma patients. Association of cytoplasmic and nuclear NHERF1 expression with survival was analyzed. Disease-free survival (DFS) and overall survival (OS) were determined based on the Kaplan–Meier method. Cytoplasmic NHERF1 expression was associated with negative progesterone receptor (PgR) ( P =0.017) and positive HER2 expression ( P =0.023). NHERF1 also showed a nuclear localization and this correlated with small tumor size ( P =0.026) and positive estrogen receptor (ER) expression ( P =0.010). Multivariate analysis identified large tumor size ( P =0.011) and nuclear NHERF1 expression ( P =0.049) to be independent prognostic variables for DFS. Moreover, the nuclear NHERF1(−)/ER(−) immunophenotype (27%) was statistically associated with large tumor size ( P =0.0276), high histological grade ( P =0.0411), PgR-negative tumors ( P