Abstract
Purpose
To investigate the relationship between microvessel density, expression of vascular endothelial growth factor A (VEGF-A) and micrometastases in peripheral blood of patients with breast cancer.
Method
Microvessel density (MVD) and expression of VEGF-A were detected by immunohistochemistry S-P. Nested RT-PCR was introduced to detect the expression of hMAM mRNA in peripheral blood of all cases.
Result
Average MVD was 28.95 ± 6.95 microvessels/100× and positive rate of VEGF-A was 64.0% (32/50) in 50 cases with breast cancer. MVD count and expression of VEGF-A were related to tumor size, metastasis of axillary lymph nodes and clinical stages (P < 0.05), independent of age and histological classification (P > 0.05). The positive rate of hMAM mRNA in peripheral blood was 34.0% (17/50), which correlated with lymphatic metastasis and clinical stages (P < 0.05), independent of pathological category, menopause and hormone receptor (P > 0.05). MVD count and positive rate of VEGF-A in breast cancer with positive expression of hMAM mRNA was obviously higher than those without hMAM mRNA expression (χ 2 = 5.766, P = 0.032; t = 5.37, P = 0.002).
Conclusions
MVD count and positive expression of VEGF-A closely correlated to hMAM mRNA released from tumor cells in the circulation. hMAM mRNA is expected to become a valuable marker for further study on micrometastases of breast cancer.
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References
Azenshtein E, Meshel T, Shina S et al (2005) The angiogenic factors CXCL8 and VEGF in breast cancer: regulation by an array of pro-malignancy factors. Cancer Lett 217:73–86
Bando H (2007) Vascular endothelial growth factor and bevacitumab in breast cancer. Breast Cancer 14:163–173
Bellon G, Martiny L, Robinet A (2004) Matrix metallopmteinases and matrikines in angiogenesis. Crit Rev Oncol Hematol 49:203–220
Bikfalvi A (2007) Tumor angiogenesis. Bull Cancer 94 (7 suppl):F193–F198
Bono AV, Celato N, Cova V et al (2002) Microvessel density in prostate carcinoma. Prostate Cancer Prostatic Dis 5:123–127
Folkman J (2007) Angiogenesis: an organizing principle for drug discovery? Nat Rev Drug Discov 6:273–286
Fox SB, Leek RD, Weekes MP et al (1995) Quantitation and prognostic value of breast cancer angiogenesis: comparison of microvessel density, Chalkley count, and computer image analysis. J Pathol 177:275–283
Gasparini G, Welder N (1997) Prognostic significance of vascular endothelial growth factor protein in node negative breast carcinoma. J Nat Cancer Inst 89:139–l47
Huang JH, Li Y, Liu L et al (2006) Lymphangiogenes and location of tumor lymphatic vessels induced by VEGF-C in primary breast cancer. J Central South Univ (Med Sci) 31:36–40
Imamura M, Yamamoto H, Nakamura N et al (2007) Prognostic significance of angiogenesis in gastrointestinal stromal tumor. Mod Pathol 20:529–537
Iruela-Arispe ML, Luque A, Lee N (2004) Thrombospondin modules and angiogenesis. Int J Biochem Cell Biol 36:1070–1078
Jennbacken K, Valbo C, Wang W et al (2005) Expression of vascular endothelial growth factor C (VEGF-C) and VEGF receptor-3 in human prostate cancer is associated with regional lymph node metastasis. Prostate 65:110–116
Jonine LB, James HG, Brooke L et al (2005) Identification of mammaglobin as a novel serum marker for breast cancer. Clin Cancer Res 11:6528–6535
Kang HF, Wang XJ, Liu XX et al (2005) Clinopathologieal significance of VEGF and nm23 expression in human breast cancer. Chin J Mod Med 15:24–27
Li S, Li J, Luo C et al (2002) Expression of human mammaglobin mRNA in peripheral blood of breast cancer and their implication. Zhonghua Wai Ke Za Zhi 40:168–170
Liu H, Wu JS, Li LH et al (2000) The expression of platelet-derived growth factor and angiogenesis in human colorectal carcinoma. Shijie Huaren Xiaohua Zazhi 8:661–664
Liu X, Fan P, Wang S et al (2005) Expression of VEGF B mRNA in treat cancer and its clinical significance. Chin J Mod Med 15:3381–3383
Miksicek RJ, Myal Y, Watson PH et al (2002) Identification of a novel breast- and salivary gland-specific mucin-like gene strongly expressed in normal and tumor human mammary epithelium. Cancer Res 62:2736–2740
Nakamura Y, Yasaoka H, Tsujimoto M et al (2005) Lymph vessel density correlates with nodal status, VEGF- C expression, and prognosis in breast cancer. Breast Cancer Res Treat 91:l25–132
Ntoulia M, Stathopoulou A, Ignatiadis M et al (2006) Detection of mammaglobin A-mRNA-positive circulating tumor cells in peripheral blood of patients with operable breast cancer with nested RT-PCR. Clin Biochem 39:879–887
Ohta Y, Nozaki Z, Nozawa H et al (2001) The predictive value of vascular endothelial growth factor and nm23 for the diagnosis of occult metastasis in non-small cell lung cancer. Jpn J Cancer Res 92:361–366
Rack B, Heinemann V, Schindlbeck C et al (2008) Metastatic breast cancer-new methods of treatment. MMW Fortschr Med 150:34–36
Robert S, Kerbel RS (2000) Tumor angiogenesis: past, present and the near future. Carcinogenesis 21:505–515
Saaristo A, Karpanen T, Alitalo K (2000) Mechanisms of angiogenesis and their use in the inhibition of tumor growth and metastasis. Oncogene 19:6122–6129
Smime C, Camandona M, Rosso E et al (1999) Vascular endothelial growth factor. From basic research to clinical application. Minerva Med 90:15–23
Viacava P, Neccarato AG, Bocci G et al (2004) Angiogenesis and VEGF expression in pre-invasive lesions of the human breast. J Pathol 204:140–146
Wang YD, Wu P, Mao JD et al (2007a) Relationship between vascular invasion and microvessel density and micrometastasis. World J Gastroenterol 13:6269–6273
Wang HP, Li GX, Qiao ZH et al (2007b) Detection of tumor load in chronic myeloid leukemia during treatment with transplantation by conventional cytogenetics, nested-RT-PCR and FISH. Zhongguo Shi Yan Xue Ye Xue Za Zhi 15:237–241
World Health Organization (1996) Research on the menopause in the 1990s. Technical report Scr 866. Geneva, Switzerland
Xu Q, Chen RX, Wang ZW et al (2005) Clinical research on angiogenisis in colorectal carcinoma and expression of CK20 mRNA in peripheral blood. Natl Med J China 85:1205–1208
Yan G, Zhou XY, Cai SJ et al (2008) Lymphangiogenic and angiogenic microvessel density in human primary sporadic colorectal carcinoma. World J Gastroenterol 7:101–107
Zhu ZH, Rong TH, Zeng CG et al (2005) Vascular endothelial growth factor expression and microvessel density in stage I-II non-small cell lung cancer and their prognostic significances. Ai Zheng 24:865–869
Acknowledgments
We thank Dr. Li Yan for providing MCF-7 cell line. We thank Prof. Liu Yongye for critical revision of the manuscript.
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Xie, XD., Qu, SX., Liu, ZZ. et al. Study on relationship between angiogenesis and micrometastases of peripheral blood in breast cancer. J Cancer Res Clin Oncol 135, 413–419 (2009). https://doi.org/10.1007/s00432-008-0473-4
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DOI: https://doi.org/10.1007/s00432-008-0473-4