Experimental Medical Oncology, NCRC Istituto Tumori "Giovanni Paolo II", Bari, Italy.
Cell Death Dis. 2013 Nov 7;4(11):e904. 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<0.0001) and high proliferative activity (P=0.0027). These patients had worse DFS compared with patients with nuclear NHERF1(+)/ER(+) tumors (75.4% versus 92.6%; P=0.010). These results show that the loss of nuclear NHERF1 expression is associated with reduced survival, and the link between nuclear NHERF1 and ER expression may serve as a prognostic marker for the routine clinical management of breast cancer patients.
我们的目的是研究钠/氢交换调节因子 1（NHERF1）的表达是否与浸润性乳腺癌的预后有关。NHERF1 是一种与 ezrin-radixin-moesin（ERM）结合的磷蛋白 50，参与将整合膜蛋白与细胞骨架连接。因此，它被认为在与细胞细胞形态变化相关的细胞信号转导中具有重要作用。NHERF1 表达在各种类型的癌症中观察到，并且与肿瘤侵袭性有关。迄今为止，对 NHERF1 在癌症发展中的影响进行的最广泛分析是在乳腺癌中进行的。然而，其潜在机制及其预后意义仍未定义。通过免疫组织化学（IHC）在 222 例乳腺癌患者队列中研究 NHERF1 的表达。分析细胞质和核 NHERF1 表达与生存的关系。基于 Kaplan-Meier 方法确定无病生存期（DFS）和总生存期（OS）。细胞质 NHERF1 表达与孕激素受体（PgR）阴性（P=0.017）和 HER2 表达阳性（P=0.023）相关。NHERF1 还显示出核定位，这与肿瘤体积小（P=0.026）和雌激素受体（ER）表达阳性（P=0.010）相关。多变量分析确定大肿瘤大小（P=0.011）和核 NHERF1 表达（P=0.049）是 DFS 的独立预后变量。此外，核 NHERF1（-）/ER（-）免疫表型（27%）与肿瘤体积大（P=0.0276）、高组织学分级（P=0.0411）、PgR 阴性肿瘤（P<0.0001）和高增殖活性（P=0.0027）相关。与核 NHERF1（+）/ER（+）肿瘤的患者相比，这些患者的 DFS 更差（75.4%比 92.6%；P=0.010）。这些结果表明，核 NHERF1 表达的丧失与生存率降低有关，核 NHERF1 与 ER 表达之间的联系可能作为乳腺癌患者常规临床管理的预后标志物。
