[Study of the correlation between HER-2 gene and lymphangiogenesis and their prognostic significance in human breast cancer]

Zhonghua Yi Xue Za Zhi. 2007 Jan 16;87(3):155-60.
[Article in Chinese]


Objective: To demonstrate the molecular mechanism of poor prognosis in HER-2 overexpressing breast carcinoma, to study the correlation between angiogenesis/lymphangiogenesis and HER-2, and the effect of them in the progression and prognosis, so as to provide novel molecular markers for lymph node metastasis and prognosis in breast carcinoma.

Methods: (1) By using TaqMan real-time quantitative reverse transcription polymerase chain reaction (real-time qRT-PCR) technique and immunohistochemistry (IHC), the mRNA and protein expression of VEGF-C were detected in SKBR-3 and MDA-MB-231 cell lines before and after the interference with Herceptin. (2) Real-time qRT-PCR was performed to detect the mRNA expression of VEGF-C and -D genes in 67 cases of primary breast infiltrating ductal carcinoma. (3) 160 formalin-fixed paraffin-embedded infiltrating ductal carcinomas were selected. The protein expression of HER-2, VEGF-C, lymphatic vessel density (LVD) and lymphatic vessel invasion (LVI) were detected by IHC.

Result: (1) After interference with Herceptin, the VEGF-C mRNA and protein expression of sKBR-3 the cells decreased significantly. In primary breast cancer, the protein expression of HER-2 was positively correlated with VEGF-C protein expression (r = 0.215, P < 0.05). There was a significantly positive correlation between VEGF-C protein expression and LVD (r = 0.248, P < 0.01). (2) VEGF-C mRNA expression in the patients with lymph node metastasis was higher than that in the patients without lymph node metastasis (1.6 +/- 0.5 vs 1.1 +/- 0.5) (t = 2.196, P < 0.05). Logistic regression model showed HER-2, LVD and LVI were important factors influencing lymph node metastasis (all P < 0.05). (3) Kaplan-Meier analysis indicated that HER-2 protein overexpression, VEGF-C protein overexpression, and high LVD and LVI were associated with patient's worse disease-free survival (P(uni) < 0.05). Cox regression analysis indicated that HER-2 and LVI were the independent prognostic factors of breast cancer (both P(mult) < 0.05).

Conclusion: Through up-regulating VEGF-C expression, HER-2 overexpression induces lymphangiogenesis, promotes metastasis, and results in the poor prognosis of breast cancer. VEGF-C expression, LVD and LVI are novel prognostic indicators of breast cancer.

Publication types

  • English Abstract
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal / pharmacology
  • Antibodies, Monoclonal, Humanized
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology*
  • Cell Line, Tumor
  • Female
  • Follow-Up Studies
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Immunohistochemistry
  • Lymphangiogenesis*
  • Lymphatic Metastasis
  • Prognosis
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptor, ErbB-2 / genetics*
  • Receptor, ErbB-2 / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Survival Analysis
  • Trastuzumab
  • Vascular Endothelial Growth Factor C / genetics
  • Vascular Endothelial Growth Factor C / metabolism


  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • RNA, Messenger
  • Vascular Endothelial Growth Factor C
  • Receptor, ErbB-2
  • Trastuzumab