The relationship between lymphatic vascular density and vascular endothelial growth factor A (VEGF-A) expression with clinical-pathological features and survival in pancreatic adenocarcinomas
详细信息    查看全文
  • 作者:Ver?nica A Zorgetto (1)
    Giórgia G Silveira (1)
    Jo?o Paulo Oliveira-Costa (1)
    Danilo F Soave (1)
    Fernando A Soares (2)
    Alfredo Ribeiro-Silva (1)
  • 关键词:Pancreatic cancer ; VEGF ; A ; Angiogenesis ; Lymphangiogenesis ; Immunohistochemistry ; Tissue microarray ; Prognosis
  • 刊名:Diagnostic Pathology
  • 出版年:2013
  • 出版时间:December 2013
  • 年:2013
  • 卷:8
  • 期:1
  • 全文大小:419 KB
  • 参考文献:1. Bevan R, Young C, Holmes P, Fortunato L, Slack R, Rushton L: Occupational cancer in Britain. Gastrointestinal cancers: liver, oesophagus, pancreas and stomach. / Br J Cancer 2012, 107:S33--S40. CrossRef
    2. Vainio H: Targeting angiogenesis -a novel mode in cancer chemoprevention. / Asian Pacific J Cancer Prev 2003, 4:83-6.
    3. Alitalo A, Detmar M: Interaction of tumor cells and lymphatic vessels in cancer progression. / Oncogene 2012, 31:4499-508. CrossRef
    4. Nagy JA, Dvorak AM, Dvorak HF: VEGF-A and the induction of pathological angiogenesis. / Annu Rev Pathol Mech Dis 2007, 2:251-75. CrossRef
    5. Whitehurst B, Flister MJ, Bagaitkar J, Volk L, Bivens CM, Pickett B, Castro-Rivera E, Brekken RA, Gerard RD, Ran S: Anti-VEFG-A therapy reduces lymphatic vessel density and expression of VEGFR-3 in an orthotopic breast tumor model. / Int J Cancer 2007, 121:2182-191. CrossRef
    6. Christiansen A, Detmar M: Lymphangiogenesis and Cancer. / Genes Cancer 2011, 2:1146-158. CrossRef
    7. Zhang LZ, Zhang CQ, Yan ZY, Yang QC, Jiang Y, Zeng BF: Tumor-initiating cells and tumor vascularization. / Pediatr Blood Cancer 2011,56(3):335-40. CrossRef
    8. Lin M, Ma SP, Lin HZ, Ji P, Xie D, Yu JX: Intratumoral as well as peritumoral lymphatic vessel invasion correlates with lymph node metastasis and unfavourable outcome in colorectal cancer. / Clin Exp Metastasis 2010,27(3):123-32. CrossRef
    9. Leong SP, Nakamura EK, Pollok R, Choti MA, Morton DL, Henner WD, Lal A, Pillai R, Clark OH, Cady B: Unique patterns of metastases in common and rare types of malignancy. / J Surg Oncol 2011,103(6):607-14. CrossRef
    10. Sharma RA, Harris AL, Dalgleish AG, Steward WP, O’Byrne KJ: Angiogenesis as a biomarker and target in cancer chemoprevention. / Lancet Oncol 2001,2(12):726-32. CrossRef
    11. Kysas PA, Geleff S, Batistatou A, Agnantis NJ, Stefanou D: Evidence for lymphangiogenesis and its prognostic implications in head and neck squamous cell carcinoma. / J Pathol 2005,206(2):170-77. CrossRef
    12. Kayser K, Schultz H, Goldmann T, G?rtler J, Kayser G, Vollmer E: Theory of sampling and its application in tissue based diagnosis. / Diagn Pathol 2009, 4:6. CrossRef
    13. Santini D, Vicenzi B, Perrone G, Rabitti C, Borzomati D, Valeri S, Coppola R, Magistrelli P, Tonini G: Vascular endothelial growth factor (VEGF) expression is not associated with prognosis in patients with radically resected ampullary carcinoma. / Ann Oncol 2005,16(11):1847-848. CrossRef
    14. Smith RA, Tang J, Tudur-Smith C, Neoptolemos JP, Ghaneh P: Meta-analysis of immunohistochemical prognostic markers in resected pancreatic cancer. / Br J Cancer 2011,104(9):1440-451. CrossRef
    15. Weidner N, Semple JP, Welch WR, Folkman J: Tumor angiogenesis and metastasis -correlation in invasive breast carcinoma. / N Engl J Med 1991,324(1):1-. CrossRef
    16. Alexiev BA, Drachenberg CB, Papadimitriou JC: Endocrine tumors of the gastrointestinal tract and pancreas: grading, tumor size and proliferation index do not predict malignant behavior. / Diagn Pathol 2007, 2:28. CrossRef
    17. Yeo TP, Lowenfels AB: Demographics and epidemiology of pancreatic cancer. / The Cancer Journal 2012,18(6):477-84. CrossRef
    18. Takikita M, Altekruse S, Lynch CF, Goodman MT, Hernandez BY, Green M, Cozen W, Cockburn M, Sibug Saber M, Topor M, Zeruto C, Abedi-Ardekani B, Reichman ME, Hewitt SM: Associations between selected biomarkers and prognosis in a populations-based pancreatic cancer tissue microarray. / Cancer Res 2009,69(7):2950-955. CrossRef
    19. Hidalgo M: Pancreatic cancer. / N Engl J Med 2010, 362:1605-617. CrossRef
    20. Kl?ppel G, Hrubau RH, Longnecker DS, Adler G, Kern SE, Partanen TJ: Ductal Adenocarcinoma of the Pancreas. In / Pathology and Genetics of Tumours of the Digestive System. Edited by: Hamilton SR, Aaltonen LA. Lyon: ARC Press; 2000:221-30.
    21. Lins TC, Vieira RG, Abreu BS, Gentil P, Moreno-Lima R, Oliveira RJ, Pereira RW: Genetic heterogeneity of self-reported ancestry groups in an admixed Brazilian population. / J Epidemiol 2011,21(4):240-45. CrossRef
    22. Oliveira LR, Jeffrey SS, Ribeiro-Silva A: Stem cells in human breast cancer. / Histol Histopathol 2010,25(3):371-85.
    23. Braun S, Bitton-Worms K, LeRoith D: The link between the metabolic syndrome and cancer. / Int J Biol Sci 2011,7(7):1003-015. CrossRef
    24. Li D: Diabetes and pancreatic cancer. / Mol Carcinog 2012,51(1):64-4. CrossRef
    25. Prizment AE, Gross M, Rasmussen-Torvik L, Peacock JM, Anderson KE: Genes related to diabetes may be associated with pancreatic cancer in a population-based case–control study in Minnesota. / Pancreas 2012,41(1):50-3. CrossRef
    26. Elena JW, Steplowski E, Yu K, Hartge P, Tobias GS, Brotzman MJ, Chanock SJ, Stolzenberg-Solomon RZ, Arslan AA, Bueno-de-Mesquita HB, Helzlsouer K, Jacobs EJ, LaCroix A, Petersen G, Zheng W, Albanes D, Allen NE, Amundadottir L, Bao Y, Boeing H, Boutron-Ruault MC, Buring JE, Gaziano JM, Giovannucci EL, Duell EJ, Hallmans G, Howard BV, Hunter DJ, Hutchinson A, Jacobs KB, / et al.: Diabetes and risk of pancreatic cancer: a pooled analysis from the pancreatic cancer cohort consortium. / Cancer Causes Control 2013,24(1):13-5. CrossRef
    27. Kayser K, Nwoye JO, Kosjerina Z, Goldmann T, Vollmer E, Kaltner H, André S, Gabius HJ: Atypical adenomatous hyperplasia of lung: its incidence and analysis of clinical, glycohistochemical and structural features including newly defined growth regulators and vascularization. / Lung Cancer 2003,42(2):171-82. CrossRef
    28. Kawauchi S, Fukuda T, Tsuneyoshi M: Angiogenesis does not correlate with prognosis or vascular endothelial growth factor in synovial sarcomas. / Oncol Rep 1999,6(5):959-023.
    29. Sullu Y, Gun S, Atmaca S, Karagoz F, Kandemir B: Poor prognostic clinicopathologic features correlate with VEGF expression but not with PTEN expression in squamous cell carcinoma of the larynx. / Diagn Pathol 2010, 5:35. CrossRef
    30. Kayser G, Baumh?kel JD, Sz?ke T, Trojan I, Riede U, Werner M, Kayser K: Vascular diffusion density and survival of patients with primary lung carcinomas. / Virchows Arch 2003,442(5):462-67.
    31. Sleeman JP, Thiele W: Tumor metastasis and the lymphatic vasculature. / Int J Cancer 2009,125(12):2747-756. CrossRef
    32. Sleeman JP, Schmid A, Thiele W: Tumor lymphatics. / Semin Cancer Biol 2009,19(5):285-97. CrossRef
    33. Rubbia-Brandt L, Terris B, Giostra E, Dousset B, Morel P, Pepper MS: Lymphatic vessel density and vascular endothelial growth factor-C expression correlate with malignant behavior in human pancreatic endocrine tumors. / Clin Cancer Res 2004,10(20):6919-928. CrossRef
    34. Sipos B, Kojima M, Tiemann K, Klapper W, Kruse ML, Kalthoff H, Schniewind B, Tepel J, Weich H, Keriaschki D, Kl?ppel G: Lymphatic spread of ductal pancreatic adenocarcinoma is independent of lymphangiogenesis. / J Pathol 2005,207(3):301-12. CrossRef
    35. Padera TP, Kadambi A, di Tomaso E, Carreira CM, Brown EB, Boucher Y, Choi NC, Mathinsen D, Wain J, Mark EJ, Jain RK: Lymphatic metastasis in the absence of functional intratumor lymphatics. / Science 2002,296(5574):1883-886. CrossRef
    36. Schopmann SF, Birner P, St?ckl J, Kalt R, Ullrich R, Cauciq C, Kriehuber E, Nagy K, Alitalo K, Keriaschki D: Tumor-associated macrophages express lymphatic endothelial growth factors and are related to peritumoral lymphangiogenesis. / Am J Pathol 2002,161(3):947-56. CrossRef
    37. Yin N, Zhang N, Lal G, Xu J, Yan M, Ding Y, Bromberg JS: Lymphangiogenesis is required for pancreatic islet inflammation and diabetes. / PLoS One 2011,6(11):e28023. CrossRef
    38. Wang Z, Wu J, Li G, Zhang X, Tong M, Wu Z, Lui Z: Lymphangiogenesis and biological behavior in pancreatic carcinoma and other pancreatic tumors. / Mol Med Rep 2012,5(4):959-63.
    39. Kerbel RS: Tumor angiogenesis: past, present and the near future. / Carcinogenesis 2000,21(3):505-15. CrossRef
    40. Folkman J: Role of angiogenesis in tumor growth and metastasis. / Semin Oncol 2002,29(6 Suppl 16):15-8.
    41. Folkman J: Angiogenesis. / Annu Rev Med 2006, 57:1-8. CrossRef
    42. Cao Y, Langer R: A review of Judah Folkman’s remarkable achievements in biomedicine. / Proc Natl Acad Sci U S A 2008,105(36):13203-3205. CrossRef
    43. Otrock ZK, Makarem JA, Shamseddine AI: Vascular endothelial growth factor family of ligands and receptors: review. / Blood Cells Mol Dis 2007,38(3):258-68. CrossRef
    44. Nowak DG, Woolard J, Amin EM, Konopatskaya O, Saleem MA, Churchill AJ, Ladomery MR, Harper SJ, Bates DO: Expression of pro- and anti-angiogenic isoforms of VEGF is differentially regulated by splicing and growth factors. / J Cell Sci 2008,121(Pt 20):3487-495. CrossRef
    45. Woolard J, Bevan HS, Harper SJ, Bates DO: Molecular diversity of VEGF-A as a regulator of its biological activity. / Microcirculation 2009,16(7):572-92. CrossRef
    46. Wirzenius M, Tammela T, Uutela M, He Y, Odorisio T, Zambruno G, Nagy JA, Dvorak HF, Yl?-Herrttuala S, Shibuya M, Alitalo K: Distinct vascular endothelial growth factor signals for lymphatic vessel enlargement and sprouting. / J Exp Med 2007,204(6):1431-440. CrossRef
    47. Liang QL, Wang BR, Chen GQ, Li GH, Xu YY: Clinical significance of vascular endothelial growth factor and connexin43 for predicting pancreatic cancer clinicopathologic parameters. / Med Oncol 2010,27(4):1164-170. CrossRef
    48. Cao Y: Why and how do tumors stimulate lymphangiogenesis? / Lymphat Res Biol 2008,6(3-):145-48. CrossRef
  • 作者单位:Ver?nica A Zorgetto (1)
    Giórgia G Silveira (1)
    Jo?o Paulo Oliveira-Costa (1)
    Danilo F Soave (1)
    Fernando A Soares (2)
    Alfredo Ribeiro-Silva (1)

    1. Departament of Pathology, Ribeir?o Preto Medical School, University of S?o Paulo, 3900 Bandeirantes Avenue, Ribeir?o Preto, S?o Paulo, Brazil
    2. Departament of Pathologic Anatomy A. C. Camargo Cancer Center S?o Paulo, S?o Paulo, Brazil
  • ISSN:1746-1596
文摘
Background Pancreatic cancer is a rare tumor with an extremely low survival rate. Its known risk factors include the chronic use of tobacco and excessive alcohol consumption and the presence of chronic inflammatory diseases, such as pancreatitis and type 2 diabetes. Angiogenesis and lymphangiogenesis, which have been the focus of recent research, are considered prognostic factors for cancer development. Knowing the angiogenic and lymphangiogenic profiles of a tumor may provide new insights for designing treatments according to the different properties of the tumor. The aim of this study was to evaluate the density of blood and lymphatic vessels, and the expression of VEGF-A, in pancreatic adenocarcinomas, as well as the relationship between blood and lymphatic vascular density and the prognostically important clinical-pathological features of pancreatic tumors. Methods Paraffin blocks containing tumor samples from 100 patients who were diagnosed with pancreatic cancer between 1990 and 2010 were used to construct a tissue microarray. VEGF expression was assessed in these samples by immunohistochemistry. To assess the lymphatic and vascular properties of the tumors, 63 cases that contained sufficient material were sectioned routinely. The sections were then stained with the D2-40 antibody to identify the lymphatic vessels and with a CD34 antibody to identify the blood vessels. The vessels were counted individually with the Leica Application Suite v4 program. All statistical analyses were performed using SPSS 18.0 (Chicago, IL, USA) software, and p values ?0.05 were considered significant. Results In the Cox regression analysis, advanced age (p=0.03) and a history of type 2 diabetes (p=0.014) or chronic pancreatitis (p=0.02) were shown to be prognostic factors for pancreatic cancer. Blood vessel density (BVD) had no relationship with clinical-pathological features or death. Lymphatic vessel density (LVD) was inversely correlated with death (p=0.002), and by Kaplan-Meyer survival analysis, we found a significant association between low LVD (p=0.021), VEGF expression (p=0.023) and low patient survival. Conclusions Pancreatic carcinogenesis is related to a history of chronic inflammatory processes, such as type 2 diabetes and chronic pancreatitis. In pancreatic cancer development, lymphangiogenesis can be considered an early event that enables the dissemination of metastases. VEGF expression and low LVD can be considered as poor prognostic factors as tumors with this profile are fast growing and highly aggressive. Virtual slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/5113892881028514

© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号

地址:北京市海淀区学院路29号 邮编:100083

电话:办公室:(+86 10)66554848;文献借阅、咨询服务、科技查新:66554700