Skip to main content
Top
Published in: Clinical & Experimental Metastasis 7/2008

01-11-2008 | Research Paper

Lymphangiogenesis induced by VEGF-C and VEGF-D promotes metastasis and a poor outcome in breast carcinoma: a retrospective study of 61 cases

Authors: Yan Gu, Xiaoliang Qi, Shanyu Guo

Published in: Clinical & Experimental Metastasis | Issue 7/2008

Login to get access

Abstract

Purpose To evaluate lymphangiogenesis in patients with breast carcinoma, explore the underlying mechanism, and study the relationship between lymphangiogenesis and progression of breast carcinoma. Methods Sixty-one cases of breast carcinoma with complete clinical and pathological data were analyzed. Using an anti-podoplanin monoclonal antibody, an immunohistochemical study was made of all specimens to detect lymphatic vessel density (LVD) and to investigate its clinicopathological and prognostic value. VEGF-C and VEGF-D were observed by RT-PCR and immunostaining to investigate their clinicopathological and prognostic values and their relationship with lymphangiogenesis. Results LVD in breast carcinoma (6.28 ± 3.73) was significantly higher than in benign mammary lesions (0.50 ± 1.27), P < 0.01 and was significantly associated with lymphatic metastasis and high TNM stage, P < 0.01. The level of VEGF-C and VEGF-D expression was also significantly higher in breast carcinomas than in benign mammary lesions, P < 0.01. LVD increased significantly with higher expression of VEGF-C and VEGF-D, P < 0.01. Patients with high expression of VEGF-C and VEGF-D were observed to be more likely to have a bad outcome, P < 0.05. Conclusions Lymphangiogenesis was significantly associated with lymph node metastasis, high TNM, and poor outcome in breast carcinoma. LVD may serve as a predictor of lymph node metastasis and a prognostic factor in breast carcinoma. VEGF-C and VEGF-D play an important role in lymphangiogenesis making the carcinoma more aggressive and leading to a poor prognosis.
Literature
1.
go back to reference Stewart B, Kleihues P (2003) International agency on research for cancer. In: World Health Organization. World Cancer Report. IARC Press, Lyon, pp 188–190 Stewart B, Kleihues P (2003) International agency on research for cancer. In: World Health Organization. World Cancer Report. IARC Press, Lyon, pp 188–190
3.
go back to reference Zheng Y, Li DL, Xiang YM et al (2001) The status and trend of breast cancer incidence in Shanghai. J Surg Concepts Pract 6:219–221 Zheng Y, Li DL, Xiang YM et al (2001) The status and trend of breast cancer incidence in Shanghai. J Surg Concepts Pract 6:219–221
6.
go back to reference Breiteneder-Geleff S, Matsui K, Soleiman A et al (1997) Podoplanin, novel 43-kd membrane protein of glomerular epithelial cells, is down-regulated in puromycin nephrosis. Am J Pathol 151:1141–1152PubMed Breiteneder-Geleff S, Matsui K, Soleiman A et al (1997) Podoplanin, novel 43-kd membrane protein of glomerular epithelial cells, is down-regulated in puromycin nephrosis. Am J Pathol 151:1141–1152PubMed
7.
go back to reference Birner P, Schindl M, Obermair A et al (2001) Lymphatic microvessel density as a novel prognostic factor in early-stage invasive cervical cancer. Int J Cancer 95:29–33. doi:10.1002/1097-0215(20010120)95:1≤29::AID-IJC1005≥3.0.CO;2-WPubMedCrossRef Birner P, Schindl M, Obermair A et al (2001) Lymphatic microvessel density as a novel prognostic factor in early-stage invasive cervical cancer. Int J Cancer 95:29–33. doi:10.1002/1097-0215(20010120)95:1≤29::AID-IJC1005≥3.0.CO;2-WPubMedCrossRef
9.
go back to reference Pepper MS (2000) Lymphangiogenesis and tumor metastasis more questions than answers. Lymphology 33:144–147PubMed Pepper MS (2000) Lymphangiogenesis and tumor metastasis more questions than answers. Lymphology 33:144–147PubMed
10.
go back to reference Pepper MS (2001) Lymphangiogenesis and tumor metastasis: myth or reality? Clin Cancer Res 7:462–468PubMed Pepper MS (2001) Lymphangiogenesis and tumor metastasis: myth or reality? Clin Cancer Res 7:462–468PubMed
11.
go back to reference Schoppmann SF, Birner P, Studer P et al (2001) Lymphatic microvessel density and lymphovascular invasion assessed by anti-podoplanin immunostaining in human breast cancer. Anticancer Res 21:2351–2355PubMed Schoppmann SF, Birner P, Studer P et al (2001) Lymphatic microvessel density and lymphovascular invasion assessed by anti-podoplanin immunostaining in human breast cancer. Anticancer Res 21:2351–2355PubMed
13.
go back to reference Breiteneder-Geleff S, Soleiman A, Kowalski H et al (1999) Angiosarcomas express mixed endothelial phenotypes of blood and lymphatic capillaries: podoplanin as a specific marker for lymphatic endothelium. Am J Pathol 154:385–394PubMed Breiteneder-Geleff S, Soleiman A, Kowalski H et al (1999) Angiosarcomas express mixed endothelial phenotypes of blood and lymphatic capillaries: podoplanin as a specific marker for lymphatic endothelium. Am J Pathol 154:385–394PubMed
14.
go back to reference Birner P, Schindl M, Obermair A et al (2000) Lymphatic microvessel density in epithelial ovarian cancer: its impact on prognosis. Anticancer Res 20:2981–2985PubMed Birner P, Schindl M, Obermair A et al (2000) Lymphatic microvessel density in epithelial ovarian cancer: its impact on prognosis. Anticancer Res 20:2981–2985PubMed
15.
go back to reference Birner P, Schindl M, Obermair A et al (2001) Lymphatic microvessel density as a novel prognostic factor in early-stage invasive cervical cancer. Int J Cancer 95:29–33. doi:10.1002/1097-0215(20010120)95:1≤29::AID-IJC1005≥3.0.CO;2-WPubMedCrossRef Birner P, Schindl M, Obermair A et al (2001) Lymphatic microvessel density as a novel prognostic factor in early-stage invasive cervical cancer. Int J Cancer 95:29–33. doi:10.1002/1097-0215(20010120)95:1≤29::AID-IJC1005≥3.0.CO;2-WPubMedCrossRef
17.
go back to reference Kato Y, Kaneko MK, Kunita A et al (2008) Molecular analysis of the pathophysiological binding of the platelet aggregation-inducing factor podoplanin to the C-type lectin-like receptor CLEC-2. Cancer Sci 99:54–61PubMed Kato Y, Kaneko MK, Kunita A et al (2008) Molecular analysis of the pathophysiological binding of the platelet aggregation-inducing factor podoplanin to the C-type lectin-like receptor CLEC-2. Cancer Sci 99:54–61PubMed
18.
26.
28.
go back to reference Nakazato T, Shingaki S, Kitamura N et al (2006) Expression level of vascular endothelial growth factor-C and -A in cultured human oral squamous cell carcinoma correlates respectively with lymphatic metastasis and angiogenesis when transplanted into nude mouse oral cavity. Oncol Rep 15:825–830PubMed Nakazato T, Shingaki S, Kitamura N et al (2006) Expression level of vascular endothelial growth factor-C and -A in cultured human oral squamous cell carcinoma correlates respectively with lymphatic metastasis and angiogenesis when transplanted into nude mouse oral cavity. Oncol Rep 15:825–830PubMed
29.
go back to reference Schietroma C, Cianfarani F, Lacal PM et al (2003) Vascular endothelial growth factor-C expression correlates with lymph node localization of human melanoma metastases. Cancer 98:789–797. doi:10.1002/cncr.11583 PubMedCrossRef Schietroma C, Cianfarani F, Lacal PM et al (2003) Vascular endothelial growth factor-C expression correlates with lymph node localization of human melanoma metastases. Cancer 98:789–797. doi:10.​1002/​cncr.​11583 PubMedCrossRef
31.
go back to reference Mohammed RAA, Green A, El-Shikh S et al (2007) Prognostic significance of vascular endothelial cell growth factors-A, -C and -D in breast cancer and their relationship with angio- and lymphangiogenesis. Br J Cancer 96:1092–1100. doi:10.1038/sj.bjc.6603678 PubMedCrossRef Mohammed RAA, Green A, El-Shikh S et al (2007) Prognostic significance of vascular endothelial cell growth factors-A, -C and -D in breast cancer and their relationship with angio- and lymphangiogenesis. Br J Cancer 96:1092–1100. doi:10.​1038/​sj.​bjc.​6603678 PubMedCrossRef
32.
37.
go back to reference Von Marschall Z, Scholz A, Stacker SA et al (2005) Vascular endothelial growth factor-D induces lymphangiogenesis and lymphatic metastasis in models of ductal pancreatic cancer. Int J Oncol 27:669–679 Von Marschall Z, Scholz A, Stacker SA et al (2005) Vascular endothelial growth factor-D induces lymphangiogenesis and lymphatic metastasis in models of ductal pancreatic cancer. Int J Oncol 27:669–679
Metadata
Title
Lymphangiogenesis induced by VEGF-C and VEGF-D promotes metastasis and a poor outcome in breast carcinoma: a retrospective study of 61 cases
Authors
Yan Gu
Xiaoliang Qi
Shanyu Guo
Publication date
01-11-2008
Publisher
Springer Netherlands
Published in
Clinical & Experimental Metastasis / Issue 7/2008
Print ISSN: 0262-0898
Electronic ISSN: 1573-7276
DOI
https://doi.org/10.1007/s10585-008-9180-4

Other articles of this Issue 7/2008

Clinical & Experimental Metastasis 7/2008 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine