Angiopoietin-2 expression in breast cancer correlates with lymph node invasion and short survival

Int J Cancer. 2003 Feb 10;103(4):466-74. doi: 10.1002/ijc.10851.


Angiogenic factors produced by tumor cells are essential for tumor growth and metastasis. In our study, the expression of Angiopoietin-1 (ANG1) and Angiopoietin-2 (ANG2) mRNA in archival human breast cancer tumor samples and in 6 breast cancer cell lines was investigated. Total RNA from biopsies of 38 breast cancer patients was extracted and ANG1 and ANG2 mRNA expression was measured by means of quantitative real-time RT-PCR (Taqman). Matching data with available clinicopathologic and biochemical data revealed a significant association between ANG2 expression and axillary lymph node invasion. Univariate and multivariate survival analysis, by means of Kaplan-Meier method and Cox's proportional hazards model, showed significant and independent association between ANG2 mRNA level and both disease-free (p < 0.0001) and overall survival (p < 0.0003). An important fact is that, notwithstanding the small number of cases examined, this association was confirmed also in the group of lymph node-negative patients (DFS, p < 0.003; OS, p < 0.020). Immunohistochemical analysis demonstrated that Ang2 is expressed by both tumor cells and endothelial elements. Expression in tumor cells was confirmed by studying a panel of human breast carcinoma cell lines in culture by RT-PCR. In ZR75.1 and T47D cells, expression of ANG2 mRNA was increased up to 10-fold by treatment with estrogen within 24 hr. Although preliminary, these data suggest a possible role of ANG2 as a prognostic factor for primary breast cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis Inducing Agents / biosynthesis*
  • Angiopoietin-1
  • Angiopoietin-2
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / mortality*
  • Disease Progression
  • Disease-Free Survival
  • Endothelial Growth Factors / biosynthesis
  • Estrogens / metabolism
  • Estrogens / pharmacology
  • Female
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization
  • Lymphatic Metastasis
  • Membrane Glycoproteins / biosynthesis
  • Multivariate Analysis
  • Prognosis
  • Proportional Hazards Models
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Time Factors
  • Tumor Cells, Cultured
  • Vascular Endothelial Growth Factor C


  • ANGPT1 protein, human
  • Angiogenesis Inducing Agents
  • Angiopoietin-1
  • Angiopoietin-2
  • Endothelial Growth Factors
  • Estrogens
  • Membrane Glycoproteins
  • RNA, Messenger
  • Vascular Endothelial Growth Factor C