The relations of vascular endothelial growth factor–C and lymph node metastasis in breast cancer patients



Vascular endothelial growth factor–C, Lymph node metastasis, Breast cancer


Aim: Breast cancer (BC) is the 2nd most common cancer worldwide and most of the cases are sporadic. BC chooses mainly the lymphatic system and axillary lymph nodes (LN) are frequently involved. Lymph node metastasis (LNM) is driven by tumor-derived lymphangiogenic growth factors, especially vascular endothelial growth factor (VEGF) family. Higher serum levels of VEGF-C have been detected in cases of BC. In the present study, we aim to investigate the expression pattern of VEGF-C in tumor specimens and the relation of VEGF-C expression with LNM by immunohistochemistry.

Methods: In this clinical, cross-sectional study, paraffin-embedded specimens were obtained from 16 female patients who had primary invasive ductal breast cancer and received surgical treatment between April 2006 and March 2007. BC tissue sections were stained with VEGF-C antibody and evaluated according to the severity and intensity of the staining. Statistical analysis was performed using SPSS version 15.0 for Windows and in all analyses, a ‘p’ value less than 0.05 was considered statistically significant and comparisons were 2-tailed.

Results: The average age at the time of diagnosis was 50 years (range: 24-82 years). In the present study, on the basis of SI and SS VEGF-C expression did not show statistically significant correlation with LNM, while calculated IRS - as a variable- was correlated with LNM. The grade of the tumor correlated neither with the VEGF-C expression nor with lymph node metastasis (p>0.05).

Conclusions: It is interesting that the correlation with VEGF-C IRS score and axillary lymph node level was found significant statistically. In the current study, we demonstrated the VEGF-C relation with LNM via IHC staining in tumoral samples of BC patients.


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Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015;136:E359–86. doi: 10.1002/ijc.29210.

Raica M, Cimpean AM, Ceausu R, Ribatti D. Lymphatic microvessel density, VEGF-C, and VEGFR-3 expression in different molecular types of breast cancer. Anticancer Res. 2011;31:1757–64.

Wu QW, She HQ, Liang J, et al. Expression and clinical significance of extracellular matrix protein 1 and vascular endothelial growth factor-C in lymphatic metastasis of human breast cancer. BMC Cancer. 2012;12:47.

Zhang B-N, Cao X-C, Chen J-Y, et al. Guidelines on the diagnosis and treatment of breast cancer (2011 edition).Gland Surgery. 2012;1(1):39-61. doi:10.3978/j.issn.2227-684X.2012.04.07.

Zhang Y, Liu J, Lin J, et al. The transcription factor GATA1 and the histone methyltransferase SET7 interact to promote VEGF-mediated angiogenesis and tumor growth and predict clinical outcome of breast cancer. Oncotarget. 2016;7:9859–75.

Wang CA, Tsai SJ. The non-canonical role of vascular endothelial growth factor-C axis in cancer progression. Exp Biol Med (Maywood). 2015;240(6):718–24. doi:10.1177/1535370215583802

Wang CA, Harrell JC, Iwanaga R, et al. Vascular endothelial growth factor C promotes breast cancer progression via a novel antioxidant mechanism that involves regulation of superoxide dismutase 3. Breast Cancer Res. 2014;16:462. doi: 10.1186/s13058-014-0462-2.

Zhao Y-C, Ni X-J, Li Y, et al. Peritumoral lymphangiogenesis induced by vascular endothelial growth factor C and D promotes lymph node metastasis in breast cancer patients. World Journal of Surgical Oncology. 2012;10:165. doi:10.1186/1477-7819-10-165.

Fakhrejahani E, Toi M. Antiangiogenesis therapy for breast cancer: an update and perspectives from clinical trials. Jpn J Clin Oncol. 2014;44(3):197–207. doi:10.1093/jjco/hyt201

Liang B, Li Y. Prognostic Significance of VEGF-C Expression in Patients with Breast Cancer: A Meta-Analysis. Iranian Journal of Public Health. 2014;43(2):128-35.

Skobe M, Hawighorst T, Jackson DG, et al. Induction of tumor lymphangiogenesis by VEGF-C promotes breast cancer metastasis. Nat Med. 2001;7:192–8. doi: 10.1038/84643.

Nakamura Y, Yasuoka H, Tsujimoto M, et al. Clinicopathological

significance of vascular endothelial growth factor-C in breast carcinoma

with long-term follow-up. Mod Pathol. 2003;16(4):309-14.

Zhang XH, Huang DP, Guo GL, et al. Coexpression of VEGF-C and COX-2 and its association with lymphangiogenesis in human breast cancer. BMC Cancer. 2008;8:4.

Zhang Z, Luo G, Tang H, et al. Prognostic significance of high VEGF-C expression for patients with breast cancer: An update meta analysis. PLoS One. 2016;11:e0165725. doi: 10.1371/journal.pone.0165725.

Schoppmann SF, Tamandl D, Roberts L, et al. HER2/neu expression correlates with vascular endothelial growth factor-C and lymphangiogenesis in lymph node-positive breast cancer. Ann Oncol. 2010;21:955–60.






Research Article

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Mungan İbrahim, Doğru O, Aygen E, Dağlı AF. The relations of vascular endothelial growth factor–C and lymph node metastasis in breast cancer patients. J Surg Med [Internet]. 2019 Feb. 25 [cited 2024 Jul. 16];3(2):124-7. Available from: