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Published in: Journal of Cancer Research and Clinical Oncology 11/2010

01-11-2010 | Original Paper

Evaluation of protein pigment epithelium-derived factor (PEDF) and microvessel density (MVD) as prognostic indicators in breast cancer

Authors: Dan Zhou, Shao-Qiang Cheng, Hong-Fei Ji, Jin-Song Wang, Hai-Tao Xu, Guo-Qiang Zhang, Da Pang

Published in: Journal of Cancer Research and Clinical Oncology | Issue 11/2010

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Abstract

Purpose

Angiogenesis, which plays an important role in tumor growth and metastasis, is regulated by a balance between angiogenic stimulators and inhibitors. Pigment epithelium-derived factor (PEDF), a secreted glycoprotein is an important inhibitor of angiogenesis. Although the precise mechanisms by which PEDF exerts its actions remain poorly understood, there is growing evidence supporting the role of PEDF as a candidate antitumor agent. In this study, we investigated the role of PEDF in breast cancer.

Methods

We investigated the correlation of PEDF protein levels with cancer progression and prognosis in patients with invasive ductal breast cancer (IDC). We used immunohistochemistry in a cohort of 119 breast cancer patients to examine the expression of PEDF protein with an anti-PEDF antibody and to measure the microvessel density (MVD) with an anti-CD34 antibody.

Results

PEDF was an endogenous inhibitor of angiogenesis in endothelial cells. Decreased intratumoral expression of PEDF was associated with a higher microvessel density (MVD), a more metastatic phenotype, and poorer clinical outcome. PEDF was positive in 43.7% patients. Patients with low PEDF expression had a significantly higher MVD count when compared with patients with high PEDF expression. In univariate and multivariate analysis, PEDF was an independent prognostic factor.

Conclusion

The inverse correlation between PEDF expression and MVD in human breast cancer suggests that low PEDF expression is associated with angiogenesis in breast cancer. PEDF expression is therefore a potentially useful prognostic marker for breast cancer.
Literature
go back to reference Bard MP, Hegmans JP, Hemmes A et al (2004) Proteomic analysis of exosomes isolated from human malignant pleural effusions. Am J Respir Cell Mol Biol 31:114–121CrossRefPubMed Bard MP, Hegmans JP, Hemmes A et al (2004) Proteomic analysis of exosomes isolated from human malignant pleural effusions. Am J Respir Cell Mol Biol 31:114–121CrossRefPubMed
go back to reference Blacque OE, Worrall DM (2002) Evidence for a direct interaction between the tumor suppressor serpin, maspin, and types and collagen. J Biol Chem 277:10783–10788CrossRefPubMed Blacque OE, Worrall DM (2002) Evidence for a direct interaction between the tumor suppressor serpin, maspin, and types and collagen. J Biol Chem 277:10783–10788CrossRefPubMed
go back to reference Cai J, Jiang WG, Grant M, Boulton M (2006a) Pigment epithelium-derived factor (PEDF) inhibits angiogenesis via regulated intracellular proteolysis of VEGFR1. J Biol Chem 281:3604–3613CrossRefPubMed Cai J, Jiang WG, Grant M, Boulton M (2006a) Pigment epithelium-derived factor (PEDF) inhibits angiogenesis via regulated intracellular proteolysis of VEGFR1. J Biol Chem 281:3604–3613CrossRefPubMed
go back to reference Cai J, Parr C, Watkins G (2006b) Decreased pigment epithelium-derived factor expression in human breast cancer progression. Clin Cancer Res 12(11):3510–3517CrossRefPubMed Cai J, Parr C, Watkins G (2006b) Decreased pigment epithelium-derived factor expression in human breast cancer progression. Clin Cancer Res 12(11):3510–3517CrossRefPubMed
go back to reference Cao Y, Paner GP, Kahn LB, Rajan PB (2004) Noninvasive carcinoma of the breast angiogenesis and cell proliferation. Arch Parhol Lab Med 128:893–896 Cao Y, Paner GP, Kahn LB, Rajan PB (2004) Noninvasive carcinoma of the breast angiogenesis and cell proliferation. Arch Parhol Lab Med 128:893–896
go back to reference Dawson DW, Volper OV, Gills P, Crawford SE, Xu H, Benedict W et al (1999) Pigment epithelium-derived factor: a potent inhibitor of angiogenesis. Science 285:245–248CrossRefPubMed Dawson DW, Volper OV, Gills P, Crawford SE, Xu H, Benedict W et al (1999) Pigment epithelium-derived factor: a potent inhibitor of angiogenesis. Science 285:245–248CrossRefPubMed
go back to reference Dhakal HP, Bassarova A, Naume B et al (2009) Breast carcinoma vascularity: a comparison of manual microvessel count and Chalkley count. Histol Histopathol 24:1049–1059PubMed Dhakal HP, Bassarova A, Naume B et al (2009) Breast carcinoma vascularity: a comparison of manual microvessel count and Chalkley count. Histol Histopathol 24:1049–1059PubMed
go back to reference Ek ET, Choong PF (2006) The role of high-dose therapy and autologous stem cell transplantation for pediatric bone and soft tissue sarcomas. Expert Rev Anticancer Ther 6(2):225–237CrossRefPubMed Ek ET, Choong PF (2006) The role of high-dose therapy and autologous stem cell transplantation for pediatric bone and soft tissue sarcomas. Expert Rev Anticancer Ther 6(2):225–237CrossRefPubMed
go back to reference Fernandez-Garcia NL, Volpert OV, Jimenez B (2007) Pigment epithelium-derived factor as a multifunctional antitumor factor. J Mol Med 85(1):15–22CrossRefPubMed Fernandez-Garcia NL, Volpert OV, Jimenez B (2007) Pigment epithelium-derived factor as a multifunctional antitumor factor. J Mol Med 85(1):15–22CrossRefPubMed
go back to reference Goldberg RM (2005) Cetuximab. Nat Rev Drug Discov (suppl 1):10–11 Goldberg RM (2005) Cetuximab. Nat Rev Drug Discov (suppl 1):10–11
go back to reference Guang-Wu H, Sunagawa M, Jie-Em L et al (2000) The relationship between microvessel density, the expression of vascular endothelial growth factor (VEGF), and the extension of nasopharyngeal carcinoma. Laryngoscope 110:2066–2069CrossRefPubMed Guang-Wu H, Sunagawa M, Jie-Em L et al (2000) The relationship between microvessel density, the expression of vascular endothelial growth factor (VEGF), and the extension of nasopharyngeal carcinoma. Laryngoscope 110:2066–2069CrossRefPubMed
go back to reference Haybittle JL, Blamey RW, Elston CW et al (1982) A prognostic index in primary breast cancer. Br J Cancer 45:361–366PubMed Haybittle JL, Blamey RW, Elston CW et al (1982) A prognostic index in primary breast cancer. Br J Cancer 45:361–366PubMed
go back to reference Jimenez B, Volpert OV (2001) Mechanistic insights on the inhibition of tumor angiogenesis. J Mol Med 78:663–672CrossRefPubMed Jimenez B, Volpert OV (2001) Mechanistic insights on the inhibition of tumor angiogenesis. J Mol Med 78:663–672CrossRefPubMed
go back to reference Kerr DG (2004) Targeting angiogenesis in cancer: clinical development of bevacizumab. Nat Clin Pract Oncol 1:39–43CrossRefPubMed Kerr DG (2004) Targeting angiogenesis in cancer: clinical development of bevacizumab. Nat Clin Pract Oncol 1:39–43CrossRefPubMed
go back to reference Notari L, Miller A, Martinez A, Amaral J, Ju M, Robinson G, Smith LE, Becerra SP (2005) Pigment epithelium-derived factor is a substrate for matrix metalloproteinase type 2 and type 9: implications for downregulation in hypoxia. Invest Ophthalmol Vis Sci 46:2736–2747CrossRefPubMed Notari L, Miller A, Martinez A, Amaral J, Ju M, Robinson G, Smith LE, Becerra SP (2005) Pigment epithelium-derived factor is a substrate for matrix metalloproteinase type 2 and type 9: implications for downregulation in hypoxia. Invest Ophthalmol Vis Sci 46:2736–2747CrossRefPubMed
go back to reference Offersen BV, Borre M, Overgaard J (2003) Quantification of angiogenesis as a prognostic marker I human carcinomas: a critical evaluation of histopathological methods for estimation of vascular density. Eur J Cancer 39:881–890CrossRefPubMed Offersen BV, Borre M, Overgaard J (2003) Quantification of angiogenesis as a prognostic marker I human carcinomas: a critical evaluation of histopathological methods for estimation of vascular density. Eur J Cancer 39:881–890CrossRefPubMed
go back to reference Ohta M, Konno H, Tanaka T et al (2003) The significance of circulating vascular endothelial growth factor (VEGF) protein in gastric cancer. Cancer Lett 192:215–225CrossRefPubMed Ohta M, Konno H, Tanaka T et al (2003) The significance of circulating vascular endothelial growth factor (VEGF) protein in gastric cancer. Cancer Lett 192:215–225CrossRefPubMed
go back to reference Parkin DM, Brey F, Ferlay J, Pisani P (2005) Global cancer statistics 2002. CA Cancer J Clin 55(2):74–108CrossRefPubMed Parkin DM, Brey F, Ferlay J, Pisani P (2005) Global cancer statistics 2002. CA Cancer J Clin 55(2):74–108CrossRefPubMed
go back to reference Seo Y, Baba H, Fukuda T, Takashima M, Sugimachi K (2000) High expression of vascular endothelial growth factor is associated with liver metastasis and a poor prognosis for patients with ductal pancreatic adenocarcinoma. Cancer 88:2239–2245CrossRefPubMed Seo Y, Baba H, Fukuda T, Takashima M, Sugimachi K (2000) High expression of vascular endothelial growth factor is associated with liver metastasis and a poor prognosis for patients with ductal pancreatic adenocarcinoma. Cancer 88:2239–2245CrossRefPubMed
go back to reference Teo NB, Shoker BS, Jarvis C, Martin L, Sloane JP, Holcombe C (2003) Angiogenesis and invasive recurrence in ductal carcinoma in situ of the breast. Eur J Cancer 39:38–44CrossRefPubMed Teo NB, Shoker BS, Jarvis C, Martin L, Sloane JP, Holcombe C (2003) Angiogenesis and invasive recurrence in ductal carcinoma in situ of the breast. Eur J Cancer 39:38–44CrossRefPubMed
go back to reference Tombran-Tink J, Johnson LV (1989) Neuronal differentiation of retinoblastoma cells induced by medium conditioned by human RPE cells. Invest Ophthalmol Vis Sci 30:1700–1707PubMed Tombran-Tink J, Johnson LV (1989) Neuronal differentiation of retinoblastoma cells induced by medium conditioned by human RPE cells. Invest Ophthalmol Vis Sci 30:1700–1707PubMed
go back to reference Uehara H, Miyamoto M, Kato K et al (2004) Expression of pigment epithelium-derived factor decrease liver metastasis and correlates with favorable prognosis for patients with ductal pancreatic adenocarcinoma. Cancer Res 64:3533–3537CrossRefPubMed Uehara H, Miyamoto M, Kato K et al (2004) Expression of pigment epithelium-derived factor decrease liver metastasis and correlates with favorable prognosis for patients with ductal pancreatic adenocarcinoma. Cancer Res 64:3533–3537CrossRefPubMed
go back to reference Vermeulen PB, Gasparini G, Fox SB, Colpaert C, Marson LP, Gion M, Belien JAM, de Waal RMW, Van Marck E, Magnani E, Weidner N, Harris AL, Dirix LY (2002) Second international consensus on the methodology and criteria of evaluation of angiogenesis quantification in solid human tumours. Eur J Cancer 38(12):1564–1579CrossRefPubMed Vermeulen PB, Gasparini G, Fox SB, Colpaert C, Marson LP, Gion M, Belien JAM, de Waal RMW, Van Marck E, Magnani E, Weidner N, Harris AL, Dirix LY (2002) Second international consensus on the methodology and criteria of evaluation of angiogenesis quantification in solid human tumours. Eur J Cancer 38(12):1564–1579CrossRefPubMed
go back to reference Viacava P, Naccarato AG, Bocci G, Fanelli G, Aretini P, Lonobile A, Evangelista G, Montruccoli G, Bevilacqua G (2004) Angiogenesis and VEGF expression in pre-invasive lesions of the human breast. J Pathol 204:140–146CrossRefPubMed Viacava P, Naccarato AG, Bocci G, Fanelli G, Aretini P, Lonobile A, Evangelista G, Montruccoli G, Bevilacqua G (2004) Angiogenesis and VEGF expression in pre-invasive lesions of the human breast. J Pathol 204:140–146CrossRefPubMed
go back to reference Weigelt B, Wessels LF, Bosma AJ, Glas AM, Nuyten DS, He YD, Dai H, Peterse JL, van’t Veer LJ (2005) No common denominator for breast cancer lymph node metastasis. Br J Cancer 93:924–932CrossRefPubMed Weigelt B, Wessels LF, Bosma AJ, Glas AM, Nuyten DS, He YD, Dai H, Peterse JL, van’t Veer LJ (2005) No common denominator for breast cancer lymph node metastasis. Br J Cancer 93:924–932CrossRefPubMed
go back to reference Weir HK, Thun MJ, Hankey BF, Rises LA, Howe HL, Wingo PA, Jemal A, Ward E, Anderson RN, Edwards BK (2003) Annual report to the nation on the status of cancer, 1975–2000, featuring the uses of surveillance data for cancer prevention and control. J Natl Cancer Inst 95:1276–1299PubMed Weir HK, Thun MJ, Hankey BF, Rises LA, Howe HL, Wingo PA, Jemal A, Ward E, Anderson RN, Edwards BK (2003) Annual report to the nation on the status of cancer, 1975–2000, featuring the uses of surveillance data for cancer prevention and control. J Natl Cancer Inst 95:1276–1299PubMed
go back to reference Zhang LJ, Chen JF, Ke Y, Mansel RE, Jiang WG (2006a) Expression of pigment epithelial derived factor is reduced in non-small cell lung cancer and is linked to clinical outcome. Int J Mol Med 17:937–944PubMed Zhang LJ, Chen JF, Ke Y, Mansel RE, Jiang WG (2006a) Expression of pigment epithelial derived factor is reduced in non-small cell lung cancer and is linked to clinical outcome. Int J Mol Med 17:937–944PubMed
go back to reference Zhang SX, Wang JJ, Gao G, Shao C, Mott R, Ma JX (2006b) Pigment epithelium-derived factor (PEDF) is an endogenous antiinflammatory factor. FASEB J 20:323–325PubMed Zhang SX, Wang JJ, Gao G, Shao C, Mott R, Ma JX (2006b) Pigment epithelium-derived factor (PEDF) is an endogenous antiinflammatory factor. FASEB J 20:323–325PubMed
Metadata
Title
Evaluation of protein pigment epithelium-derived factor (PEDF) and microvessel density (MVD) as prognostic indicators in breast cancer
Authors
Dan Zhou
Shao-Qiang Cheng
Hong-Fei Ji
Jin-Song Wang
Hai-Tao Xu
Guo-Qiang Zhang
Da Pang
Publication date
01-11-2010
Publisher
Springer-Verlag
Published in
Journal of Cancer Research and Clinical Oncology / Issue 11/2010
Print ISSN: 0171-5216
Electronic ISSN: 1432-1335
DOI
https://doi.org/10.1007/s00432-010-0830-y

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