title: Aberrant expression of δ-like ligand 4 contributes significantly to axillary lymph node metastasis and predicts postoperative outcome in breast cancer.
abstract: 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.
authors.affiliation: Department of Breast Surgery, the Affiliated Tumor Hospital of Harbin Medical University, Harbin 150081, China.
authors.forename: Min
authors.initials: M
authors.lastname: Xiao
authors.affiliation: Gynecological Radiotherapy, the Affiliated Tumor Hospital of Harbin Medical University, Harbin 150081, China.
authors.forename: ShanShan
authors.initials: S
authors.lastname: Yang
authors.affiliation: Pathology, the Affiliated Tumor Hospital of Harbin Medical University, Harbin 150081, China.
authors.forename: XiaoMing
authors.initials: X
authors.lastname: Ning
authors.affiliation: Department of Breast Surgery, the Affiliated Tumor Hospital of Harbin Medical University, Harbin 150081, China. Electronic address: doctor_hyx@126.com.
authors.forename: YuanXi
authors.initials: Y
authors.lastname: Huang
mesh_terms: D000368:Aged; D001365:Axilla; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008198:Lymph Nodes / Q000378:metabolism / Q000473:pathology*; D008207:Lymphatic Metastasis / Q000473:pathology*; D008565:Membrane Proteins / Q000378:metabolism*; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D016019:Survival Analysis
chemical_list: D014408:Biomarkers, Tumor; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C064045:delta protein
keywords: Axillary lymph node metastasis; Breast cancer; Immunohistochemistry; δ-like ligand 4