Kulkarni Geeta, Turbin Dmitry A, Amiri Anahita, Jeganathan Sujeeve, Andrade-Navarro Miguel A, Wu Thomas D, Huntsman David G, Lee Jonathan M
Department of Biochemistry, Microbiology and Immunology, University of Ottawa, 451 Smyth Road, K1H 8M5 Ottawa, ON, Canada.
Breast Cancer Res Treat. 2007 Mar;102(1):31-41. doi: 10.1007/s10549-006-9315-8. Epub 2006 Aug 9.
Breast cancer is the most common malignancy among North American women. The identification of factors that predict outcome is key to individualized disease management and to our understanding of breast oncogenesis. We have analyzed mRNA expression of protein elongation factor eEF1A2 in two independent breast tumor populations of size n = 345 and n = 88, respectively. We find that eEF1A2 mRNA is expressed at a low level in normal breast epithelium but is detectably expressed in approximately 50-60% of primary human breast tumors. We have derived an eEF1A2-specific antibody and measured eEF1A2 protein expression in a sample of 438 primary breast tumors annotated with 20-year survival data. We find that high levels of eEF1A2 protein are detected in 60% of primary breast tumors independent of HER-2 protein expression, tumor size, lymph node status, and estrogen receptor (ER) expression. Importantly, we find that high eEF1A2 is a significant predictor of outcome. Women whose tumor has high eEF1A2 protein expression have an increased probability of 20-year survival compared to those women whose tumor does not express substantial eEF1A2. In addition, eEF1A2 protein expression predicts increased survival probability in those breast cancer patients whose tumor is HER-2 negative or who have lymph node involvement.
乳腺癌是北美女性中最常见的恶性肿瘤。识别预测预后的因素是个体化疾病管理以及我们理解乳腺肿瘤发生机制的关键。我们分别分析了两个独立的乳腺肿瘤群体(样本量分别为n = 345和n = 88)中蛋白质延伸因子eEF1A2的mRNA表达。我们发现,eEF1A2 mRNA在正常乳腺上皮中低水平表达,但在约50%-60%的原发性人类乳腺肿瘤中可检测到表达。我们制备了一种eEF1A2特异性抗体,并在438例标注了20年生存数据的原发性乳腺肿瘤样本中检测了eEF1A2蛋白表达。我们发现,60%的原发性乳腺肿瘤中检测到高水平的eEF1A2蛋白,且与HER-2蛋白表达、肿瘤大小、淋巴结状态和雌激素受体(ER)表达无关。重要的是,我们发现高eEF1A2是预后的一个重要预测指标。与肿瘤未大量表达eEF1A2的女性相比,肿瘤eEF1A2蛋白表达高的女性20年生存概率增加。此外,eEF1A2蛋白表达预测了那些肿瘤为HER-2阴性或有淋巴结转移的乳腺癌患者生存概率的增加。