Xiao Min, Yang ShanShan, Ning XiaoMing, Huang YuanXi
Department of Breast Surgery, the Affiliated Tumor Hospital of Harbin Medical University, Harbin 150081, China.
Gynecological Radiotherapy, the Affiliated Tumor Hospital of Harbin Medical University, Harbin 150081, China.
Hum Pathol. 2014 Nov;45(11):2302-10. doi: 10.1016/j.humpath.2014.04.025. Epub 2014 Aug 13.
δ-Like ligand 4 (DLL4), a ligand for the Notch family of receptors, forecasts the prognosis of several human malignancies. However, the expression and role of DLL4 in breast cancer remain largely unknown. In the present study, we first evaluated whether the overexpression of DLL4 could be used as an indicator of axillary lymph node metastasis and postoperative prognosis in breast cancer. The amount of DLL4 protein was assessed in 204 tumor specimens by immunohistochemical staining. Overexpression was detected in 142 (69.6%) and significantly associated with advanced TNM stage (III versus I, P = .031; III versus II, P = .038), axillary lymph node metastasis (P = .001), and postoperative recurrence (P = .007). Moreover, using univariate and multivariate logistic regression analysis, we found that DLL4 overexpression was strongly associated with axillary lymph node metastasis (odds ratio, 3.036; 95% confidence interval [CI], 1.561, 5.902; P = .001). Lastly, survival analysis showed that patients with low DLL4 expression had a significantly better overall survival and disease-free survival than patients with high DLL4 expression. Furthermore, in multivariate analysis, DLL4 overexpression was an independent risk factor for unfavorable overall survival (hazard ratio, 2.662; 95% CI, 1.300, 5.452; P = .007) and disease-free survival (hazard ratio, 2.568; 95% CI, 1.353, 4.876; P = .004). Taken together, these results suggest that high expression of DLL4 is associated with axillary lymph node metastasis and a poor prognosis in breast cancer, suggesting its value as a diagnostic marker for breast cancer.
δ样配体4（DLL4）是Notch受体家族的一种配体，可预测多种人类恶性肿瘤的预后。然而，DLL4在乳腺癌中的表达及作用仍 largely未知。在本研究中，我们首先评估DLL4的过表达是否可作为乳腺癌腋窝淋巴结转移及术后预后的指标。通过免疫组织化学染色在204个肿瘤标本中评估DLL4蛋白的量。在142个标本（69.6%）中检测到过表达，且与晚期TNM分期（III期与I期，P = 0.031；III期与II期，P = 0.038）、腋窝淋巴结转移（P = 0.001）及术后复发（P = 0.007）显著相关。此外，使用单因素和多因素逻辑回归分析，我们发现DLL4过表达与腋窝淋巴结转移密切相关（优势比，3.036；95%置信区间[CI]，1.561，5.902；P = 0.001）。最后，生存分析表明，DLL4低表达患者的总生存期和无病生存期明显优于DLL4高表达患者。此外，在多因素分析中，DLL4过表达是总生存期不良（风险比，2.662；95%CI，1.300，5.452；P = 0.007）和无病生存期不良（风险比，2.568；95%CI，1.353，4.876；P = 0.004）的独立危险因素。综上所述，这些结果表明DLL4的高表达与乳腺癌腋窝淋巴结转移及不良预后相关，提示其作为乳腺癌诊断标志物的价值。
