Schoppmann Sebastian F, Schindl Monika, Bayer Guenther, Aumayr Klaus, Dienes Julia, Horvat Reinhard, Rudas Margaretha, Gnant Michael, Jakesz Raimund, Birner Peter
Department of Surgery, University of Vienna, Vienna, Austria.
Int J Cancer. 2003 May 10;104(6):677-82. doi: 10.1002/ijc.11009.
Id-1 is an important regulator of cellular growth and differentiation and controls malignant progression of breast cancer cells. The aim of our study was to assess the clinical impact of Id-1 expression in breast cancer, i.e., its potential impact on prognosis and prediction of treatment response. Id-1 protein expression was determined immunohistochemically in 191 patients with lymph-node negative breast cancer, and univariate and multivariate survival analysis was carried out. Fifteen (7.9%) specimens showed strong expression, 75 (39.3%) moderate, 55 (28.8%) weak expression and 46 (24.1%) cases no expression of Id-1. Patients with strong or moderate Id-1 expression had a significant shorter overall (p = 0.003, Cox regression) and disease-free survival (p = 0.01, Cox regression) compared to those with absent or low expression. Progesterone receptor density was significantly higher in breast cancers with absent/low Id-1 expression compared to those with moderate/strong expression (p < 0.001, t-test). Id-1 expression was significantly stronger in cases positive for p16(INK4a) expression compared to those negative for p16 (p = 0.049, Mann-Whitney test). The influence of Id-1 on clinical outcome seems much stronger in patients with negative estrogen receptor status compared to those with positive status, who received receptor antagonists as adjuvant therapy in most cases. Overexpression of Id-1 protein represents a strong independent prognostic marker in node negative breast cancer, and future therapies inhibiting Id-1 expression might be beneficial for these patients. Our results also suggest that due to the apparent interaction of Id-1 with the steroid-receptor system in breast cancer, hormonal therapies might influence Id-1 expression and its impact on clinical outcome.
Id-1是细胞生长和分化的重要调节因子，控制着乳腺癌细胞的恶性进展。我们研究的目的是评估Id-1在乳腺癌中的临床影响，即其对预后和治疗反应预测的潜在影响。通过免疫组织化学方法测定了191例淋巴结阴性乳腺癌患者的Id-1蛋白表达，并进行了单因素和多因素生存分析。15例（7.9%）标本显示Id-1强表达，75例（39.3%）中度表达，55例（28.8%）弱表达，46例（24.1%）无表达。与无表达或低表达的患者相比，Id-1强表达或中度表达的患者总生存期（p = 0.003，Cox回归）和无病生存期（p = 0.01，Cox回归）显著缩短。与中度/强表达的乳腺癌相比，Id-1无表达/低表达的乳腺癌中孕激素受体密度显著更高（p < 0.001，t检验）。与p16阴性的病例相比，p16（INK4a）表达阳性的病例中Id-1表达显著更强（p = 0.049，Mann-Whitney检验）。与雌激素受体阳性的患者相比，雌激素受体阴性的患者中Id-1对临床结局的影响似乎更强，大多数情况下雌激素受体阳性的患者接受受体拮抗剂作为辅助治疗。Id-1蛋白的过表达是淋巴结阴性乳腺癌中一个强大的独立预后标志物，未来抑制Id-1表达的治疗可能对这些患者有益。我们的结果还表明，由于Id-1与乳腺癌中类固醇受体系统的明显相互作用，激素疗法可能会影响Id-1表达及其对临床结局的影响。
