Prognostic role of HuR in hereditary breast cancer
Prognostic role of HuR in hereditary breast cancer
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DOI：
10.1158/1078-0432.ccr-07-1432
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发表时间：
2007-12-01
影响因子：
11.5
通讯作者：
Ristimaki, Ari
中科院分区：
文献类型：
--
作者：
Heinonen, Mira;Fagerholm, Rainer;Ristimaki, Ari
目的：HuR是一种mRNA结合蛋白，可增强某些转录物的稳定性并调节其翻译。HuR蛋白质的细胞质表达升高与癌发生有关，并与乳腺癌、卵巢癌和胃腺癌的生存率降低有关。肿瘤样本收集自具有确定的BRCA 1（n = 51）或BRCA 2（n = 47）突变的患者或家族性非BRCA 1/2病例（n = 525），并通过免疫组织化学进行分析。在家族性非BRCA 1/2乳腺癌患者中，39.4%的病例存在胞浆HuR蛋白表达，并且与雌激素受体阴性相关，孕激素受体阴性、p53阳性、高肿瘤级别和导管型肿瘤。在多变量分析中，细胞质HuR表达是非BRCA 1/2组中生存率降低的独立标志物，肿瘤大小> 2 cm，淋巴结转移和高组织学分级沿着。在BRCA 1或BRCA 2突变的患者，胞浆HuR表达更频繁（62.7%的BRCA 1和61.7%的BRCA 2）比在非BRCA 1/ 2组，但在BRCA突变的亚组胞浆HuR表达并不与survival.Conclusions：我们的研究结果表明，HuR是一个重要的预后因素，在家族性乳腺癌患者，并可能有助于在这种疾病的致癌作用。
Purpose: HuR is an mRNA-binding protein that enhances the stability of certain transcripts and can regulate their translation. Elevated cytoplasmic expression of HuR protein has been linked to carcinogenesis and is associated with reduced survival in breast, ovarian, and gastric adenocarcinomas.Experimental Design: Here, we have explored the relevance of HuR in familial breast cancer. Tumor samples were collected from patients with identified BRCA1 (n = 51) or BRCA2 (n = 47) mutations or familial non-BRCA1/2 cases (n = 525), and analyzed by immunohistochemistry.Results: Among familial non-BRCA1/2 breast cancer patients, cytoplasmic HuR protein expression was present in 39.4% of the cases and was associated with estrogen receptor negativity, progesterone receptor negativity, p53 positivity, high tumor grade, and ductal type of the tumor. In multivariate analysis, cytoplasmic HuR expression was an independent marker of reduced survival in the non-BRCA1/2 group along with tumor size > 2 cm, lymph node metastasis, and high histologic grade. In patients with BRCA1 or BRCA2 mutations, cytoplasmic HuR expression was more frequent (62.7% for BRCA1 and 61.7% for BRCA2) than in the non-BRCA1/ 2 group, but in BRCA-mutated subgroups cytoplasmic HuR expression did not associate with survival.Conclusions: Our results show that HuR is an important prognostic factor in familial breast cancer patients and may contribute to carcinogenesis in this disease.