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High microvessel density in pancreatic ductal adenocarcinoma is associated with high grade

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Abstract

The objectives of this work are to study angiogenesis in pancreatic ductal adenocarcinoma using computerized morphometric and image analysis and to compare the microvascular density in intratumoral and peritumoral areas and normal pancreatic tissue. Microvascular density was analyzed in 60 cases of pancreatic ductal adenocarcinoma and 30 samples of normal pancreatic tissue using an avidin–biotin immunoperoxidase technique with an anti-CD31 antibody. Microvascular density (MVD) was analyzed through digital microimaging and computerized analysis. The blood vessel density in the tumor was significantly higher than in peritumoral areas and in normal pancreatic tissue. Well differentiated pancreatic ductal adenocarcinomas contained higher MVD than poorly differentiated carcinomas. In pancreatic adenocarcinoma, MVD is higher than in peritumoral tissue or normal pancreatic tissue.

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References

  1. Jemal A, Siegel R, Ward E et al (2008) Cancer statistics. Cancer J Clin 58:71–96

    Article  Google Scholar 

  2. Chu GC, Kimmelman AC, Hezel A, DePinho RA (2007) Stromal biology of pancreatic cancer. J Cell Biochem 101:887–907

    Article  PubMed  CAS  Google Scholar 

  3. Mahadevan D, Von Hoff DD (2007) Tumor stroma interactions in pancreatic ductal adenocarcinoma. Mol Cancer Ther 6:1186–1197

    Article  PubMed  CAS  Google Scholar 

  4. Whatcott CJ, Han H, Posner RG et al (2011) Targeting the tumor microenvironment in cancer: why hyaluronidase deserves a second look. Cancer Discov 1:291–296

    Article  PubMed  CAS  Google Scholar 

  5. Vasseur S, Tomasini R, Tournaire R et al (2010) Hypoxia induced tumor metabolic switch contributes to pancreatic cancer aggressiveness. Cancers 2:2138–2152

    Article  CAS  Google Scholar 

  6. Masamune A, Shimosegawa T (2009) Signal transduction in pancreatic stellate cells. J Gastroenterol 44:249–260

    Article  PubMed  Google Scholar 

  7. Erkan M, Reiser-Erkan C, Michalski CW et al (2009) Cancer stellate-cells interactions perpetuate the hypoxia fibrosis cycle in pancreatic ductal adenocarcinoma. Neoplasia 11:497–508

    PubMed  CAS  Google Scholar 

  8. Koong AC, Mehta VK, Le QT et al (2000) Pancreatic tumors show high levels of hypoxia. Int J Radiat Oncol Biol Phys 48:919–922

    Article  PubMed  CAS  Google Scholar 

  9. Apte MV, Park S, Phillips PA et al (2004) Desmoplastic reaction in pancreatic cancer: role of pancreatic stellate cells. Pancreas 29:179–187

    Article  PubMed  CAS  Google Scholar 

  10. Brizel DM, Scully SP, Harrelson JM et al (1996) Tumor oxygenation predicts for the likelihood of distant metastases in human soft tissue sarcoma. Cancer Res 56:941–943

    PubMed  CAS  Google Scholar 

  11. Hockel M, Schlenger K, Aral B et al (1996) Association between tumor hypoxia and malignant progression in advanced cancer of the uterine cervix. Cancer Res 56:4509–4515

    PubMed  CAS  Google Scholar 

  12. Svagzdys S, Lesauskaite V, Pavalkis D et al (2009) Microvessel density as a new prognostic marker after radiotherapy in rectal cancer. BMC Cancer 9:95

    Article  PubMed  Google Scholar 

  13. Ravazoula P, Hatjikondi O, Maragoudakis M et al (1996) Angiogenesis and metastatic potential in breast carcinoma. Breast 5:418–421

    Article  Google Scholar 

  14. Weidner N (1995) Current pathologic methods for measuring intratumoral microvessel density within breast carcinoma and other solid tumors. Breast Cancer Res Treat 36:169–180

    Article  PubMed  CAS  Google Scholar 

  15. Uzzan B, Nicolas P, Cucherat M et al (2004) Microvessel density as a prognostic factor in women with breast cancer: a systematic review of the literature and meta-analysis. Cancer Res 64:2941–2955

    Article  PubMed  CAS  Google Scholar 

  16. Zhao H-C, Qin R, Chen X-X et al (2006) Microvessel density is a prognostic marker of human gastric cancer. World J Gastroenterol 12:7598–7603

    PubMed  Google Scholar 

  17. Han H, Silverman JF, Santucci TS et al (2001) Vascular endothelial growth factor expression in stage I non-small cell lung cancer correlates with neoangiogenesis and a poor prognosis. Ann Surg Oncol 8:72–79

    Article  PubMed  CAS  Google Scholar 

  18. Takagi K, Takada T, Amano H (2005) A high peripheral microvessel density count correlates with a poor prognosis in pancreatic cancer. J Gastroenterol 40:402–408

    Article  PubMed  Google Scholar 

  19. Ikeda N, Adachi M, Taki T et al (1999) Prognostic significance of angiogenesis in human pancreatic cancer. Br J Cancer 79:1553–1563

    Article  PubMed  CAS  Google Scholar 

  20. Ueda T, Oda T, Kinoshita T et al (2002) Neovascularization in pancreatic ductal adenocarcinoma: microvessel count analysis, comparison with non-cancerous regions and other types of carcinomas. Oncol Rep 9:239–245

    PubMed  Google Scholar 

  21. Karademir S, Sokmen S, Terzi C et al (2000) Tumor angiogenesis as a prognostic predictor in pancreatic cancer. J Hepatobiliary Pancreat Surg 7:489–495

    Article  PubMed  CAS  Google Scholar 

  22. Van der Zee JA, Van Eijck CH, Hop WC et al (2011) Angiogenesis: a prognostic determinant in pancreatic cancer? Eur J Cancer 47:2576–2584

    Article  PubMed  Google Scholar 

  23. Hsu SM, Raine L, Fanger H (1981) Use of avidin-biotin peroxidase complex (ABC) in immunoperoxidase techniques. J Histochem Cytochem 29:577–580

    Article  PubMed  CAS  Google Scholar 

  24. Kloppel G, Luttges J (2001) WHO classification 2000: exocrine pancreas tumor. VerhandlugenderDeutschenGesellschaft fur Pathologie 85:219–228

    CAS  Google Scholar 

  25. Sobin LH, Wittekind C (eds) (2002) TNM classification of malignant tumours, 6th ed. Wiley-Liss, Baltimore

    Google Scholar 

  26. Edge SB, Byrd DR, Compton CC et al (2010) Exocrine and endocrine pancreas. AJCC cancer staging manual, 7th edn. Springer, New York, pp 241–249

    Google Scholar 

  27. Folkman J (1995) Angiogenesis in cancer, vascular, rheumatoid and other disease. Nat Med 1:27–31

    Article  PubMed  CAS  Google Scholar 

  28. Weidner N (2003) Angiogenesis as a predictor of clinical outcome in cancer patients. Hum Pathol 31:403–405

    Article  Google Scholar 

  29. Weidner N (2001) Tumor vascularity: what does it tell us about the growth and spread of cancer? In: D’Amore PA, Voest E (eds) Tumor angiogenesis and microcirculation. Marcel Dekker, New York, pp 465–486

    Google Scholar 

  30. Pluda JM, Parkinson DR (1996) Clinical implications of tumor-associated neovascularisation and current antiangiogenic strategies of the treatment of malignancies of pancreas. Cancer 78:680–687

    PubMed  CAS  Google Scholar 

  31. Linder S, Blasjo M, von Rosen A et al (2001) Pattern of distribution and prognostic value of angiogenesis in pancreatic duct carcinoma: a semiquantitative immunohistochemical study of 45 patients. Pancreas 22:240–247

    Article  PubMed  CAS  Google Scholar 

  32. Khan AW, Dhillon AP, Hutchins R et al (2002) Prognostic significance of intratumoral microvessel density (IMD) in resected pancreatic and ampullary cancers to standard histopathological variables and survival. Eur J Surg Oncol 28:637–644

    Article  PubMed  CAS  Google Scholar 

  33. Takagi K, Takada T, Amano H et al (2005) Analysis of microvessels in pancreatic cancer: by light microscopy, confocal laser scan microscopy, and electron microscopy. J Gastroenterol 40(4):402–408

    Article  PubMed  Google Scholar 

  34. Rzepko R, JaskiewiczK KM et al (2003) Microvascular density in chronic pancreatitis and pancreatic ductal adenocarcinoma. Folia Histochem Cytobyol 41:237–239

    Google Scholar 

  35. Vermeulen PB, Gasparini G, Fox SB et al (1996) Quantification of angiogenesis in solid human tumors: in international consensus on the methodology and criteria of evaluation. Eur J Cancer 32:2474–2484

    Article  Google Scholar 

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Acknowledgments

This study was carried out with support from the Junta Asociada Provincial of the AECC, Valencia, Spain, and “Gent per Gent” Foundation.

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We declare that we have no conflict of interest.

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Correspondence to Anca Barău.

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Barău, A., Ruiz-Sauri, A., Valencia, G. et al. High microvessel density in pancreatic ductal adenocarcinoma is associated with high grade. Virchows Arch 462, 541–546 (2013). https://doi.org/10.1007/s00428-013-1409-1

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  • DOI: https://doi.org/10.1007/s00428-013-1409-1

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