Tumor Biology

, Volume 35, Issue 3, pp 2769–2776 | Cite as

Lack of association of microvessel density with prognosis of renal cell carcinoma: evidence from meta-analysis

  • Bing Zhang
  • Hong Ji
  • Dongliang Yan
  • Shaoqing Liu
  • Benkang Shi
Research Article


To investigate microvessel density (MVD) and its association with prognosis of renal cell carcinoma (RCC) by means of a meta-analysis. We obtained published studies and extracted appropriate data, then did a meta-analysis to estimate the predictive role of MVD by combining estimated effect-size from individual studies. Analyses for overall survival (OS) and cancer-specific survival (CSS) were performed, separately. Subgroup analysis stratified by biomarkers were also performed for studies using CD34, factor VIII-related antigen (F VIII) and others, respectively. A total of 20 studies were included for meta-analyses including nine (four for F VIII, three for CD34, and two for others) for OS and 11 (two for F VIII, seven for CD34 and two for others) for CSS. There was no significance of MVD predicting OS or CSS of RCC. The pooled HR for OS was 0.910 (95 % CI 0.824–1.006; P = 0.065) and CSS was 0.977 (95 % CI: 0.915–1.043; P = 0.487). We failed to observe significant association between MVD and prognosis of RCC. Additional studies are needed to provide more precise evidences to support our results.


Renal cell carcinoma Microvessel density Prognostic factors Survival 



We thank all the authors of primary studies that are included in our meta-analyses.

Conflicts of interest



  1. 1.
    Greenlee RT, Hill-Harmon MB, Murray T, Thun M. Cancer statistics, 2001. CA Cancer J Clin. 2001;51:15–36.PubMedCrossRefGoogle Scholar
  2. 2.
    Yildiz E, Ayan S, Goze F, Gokce G, Gultekin EY. Relation of microvessel density with microvascular invasion, metastasis and prognosis in renal cell carcinoma. BJU Int. 2008;101:758–64.PubMedCrossRefGoogle Scholar
  3. 3.
    Rioux-Leclercq N, Epstein JI, Bansard JY, Turlin B, Patard JJ, Manunta A, et al. Clinical significance of cell proliferation, microvessel density, and cd44 adhesion molecule expression in renal cell carcinoma. Hum Pathol. 2001;32:1209–15.PubMedCrossRefGoogle Scholar
  4. 4.
    Imao T, Egawa M, Takashima H, Koshida K, Namiki M. Inverse correlation of microvessel density with metastasis and prognosis in renal cell carcinoma. Int J Urol. 2004;11:948–53.PubMedCrossRefGoogle Scholar
  5. 5.
    Weidner N, Semple JP, Welch WR, Folkman J. Tumor angiogenesis and metastasis—correlation in invasive breast carcinoma. N Engl J Med. 1991;324:1–8.PubMedCrossRefGoogle Scholar
  6. 6.
    Uzzan B, Nicolas P, Cucherat M, Perret GY. Microvessel density as a prognostic factor in women with breast cancer: a systematic review of the literature and meta-analysis. Cancer Res. 2004;64:2941–55.PubMedCrossRefGoogle Scholar
  7. 7.
    Zubac DP, Bostad L, Kihl B, Seidal T, Wentzel-Larsen T, Haukaas SA. The expression of thrombospondin-1 and p53 in clear cell renal cell carcinoma: its relationship to angiogenesis, cell proliferation and cancer specific survival. J Urol. 2009;182:2144–9.PubMedCrossRefGoogle Scholar
  8. 8.
    Nativ O, Sabo E, Reiss A, Wald M, Madjar S, Moskovitz B. Clinical significance of tumor angiogenesis in patients with localized renal cell carcinoma. Urology. 1998;51:693–6.PubMedCrossRefGoogle Scholar
  9. 9.
    Delahunt B, Bethwaite PB, Thornton A. Prognostic significance of microscopic vascularity for clear cell renal cell carcinoma. Br J Urol. 1997;80:401–4.PubMedCrossRefGoogle Scholar
  10. 10.
    Yao X, Qian CN, Zhang ZF, Tan MH, Kort EJ, Yang XJ, et al. Two distinct types of blood vessels in clear cell renal cell carcinoma have contrasting prognostic implications. Clin Cancer Res. 2007;13:161–9.PubMedCrossRefGoogle Scholar
  11. 11.
    Verheul HM, van Erp K, Homs MY, Yoon GS, van der Groep P, Rogers C, et al. The relationship of vascular endothelial growth factor and coagulation factor (fibrin and fibrinogen) expression in clear cell renal cell carcinoma. Urology. 2010;75:608–14.PubMedCrossRefGoogle Scholar
  12. 12.
    Minardi D, Lucarini G, Mazzucchelli R, Milanese G, Natali D, Galosi AB, et al. Prognostic role of Fuhrman grade and vascular endothelial growth factor in pT1a clear cell carcinoma in partial nephrectomy specimens. J Urol. 2005;174:1208–12.PubMedCrossRefGoogle Scholar
  13. 13.
    MacLennan GT, Bostwick DG. Microvessel density in renal cell carcinoma: lack of prognostic significance. Urology. 1995;46:27–30.PubMedCrossRefGoogle Scholar
  14. 14.
    Parmar MK, Torri V, Stewart L. Extracting summary statistics to perform meta-analyses of the published literature for survival endpoints. Stat Med. 1998;17:2815–34.PubMedCrossRefGoogle Scholar
  15. 15.
    Toge H, Inagaki T, Kojimoto Y, Shinka T, Hara I. Angiogenesis in renal cell carcinoma: the role of tumor-associated macrophages. Int J Urol. 2009;16:801–7.PubMedCrossRefGoogle Scholar
  16. 16.
    Minardi D, Lucarini G, Filosa A, Milanese G, Zizzi A, Di Primio R, et al. Prognostic role of tumor necrosis, microvessel density, vascular endothelial growth factor and hypoxia inducible factor-1alpha in patients with clear cell renal carcinoma after radical nephrectomy in a long term follow-up. Int J Immunopathol Pharmacol. 2008;21:447–55.PubMedGoogle Scholar
  17. 17.
    Sandlund J, Hedberg Y, Bergh A, Grankvist K, Ljungberg B, Rasmuson T. Endoglin (cd105) expression in human renal cell carcinoma. BJU Int. 2006;97:706–10.PubMedCrossRefGoogle Scholar
  18. 18.
    Joo HJ, Oh DK, Kim YS, Lee KB, Kim SJ. Increased expression of caveolin-1 and microvessel density correlates with metastasis and poor prognosis in clear cell renal cell carcinoma. BJU Int. 2004;93:291–6.PubMedCrossRefGoogle Scholar
  19. 19.
    Yagasaki H, Kawata N, Takimoto Y, Nemoto N. Histopathological analysis of angiogenic factors in renal cell carcinoma. Int J Urol. 2003;10:220–7.PubMedCrossRefGoogle Scholar
  20. 20.
    Miyata Y, Koga S, Kanda S, Nishikido M, Hayashi T, Kanetake H. Expression of cyclooxygenase-2 in renal cell carcinoma: correlation with tumor cell proliferation, apoptosis, angiogenesis, expression of matrix metalloproteinase-2, and survival. Clin Cancer Res. 2003;9:1741–9.PubMedGoogle Scholar
  21. 21.
    Schraml P, Struckmann K, Hatz F, Sonnet S, Kully C, Gasser T, et al. Vhl mutations and their correlation with tumour cell proliferation, microvessel density, and patient prognosis in clear cell renal cell carcinoma. J Pathol. 2002;196:186–93.PubMedCrossRefGoogle Scholar
  22. 22.
    Sabo E, Boltenko A, Sova Y, Stein A, Kleinhaus S, Resnick MB. Microscopic analysis and significance of vascular architectural complexity in renal cell carcinoma. Clin Cancer Res. 2001;7:533–7.PubMedGoogle Scholar
  23. 23.
    Song KH, Song J, Jeong GB, Kim JM, Jung SH, Song J. Vascular endothelial growth factor - its relation to neovascularization and their significance as prognostic factors in renal cell carcinoma. Yonsei Med J. 2001;42:539–46.PubMedGoogle Scholar
  24. 24.
    Lee JS, Kim HS, Jung JJ, Park CS, Lee MC. Expression of vascular endothelial growth factor in renal cell carcinoma and the relation to angiogenesis and p53 protein expression. J Surg Oncol. 2001;77:55–60.PubMedCrossRefGoogle Scholar
  25. 25.
    Yoshino S, Kato M, Okada K. Evaluation of the prognostic significance of microvessel count and tumor size in renal cell carcinoma. Int J Urol. 1998;5:119–23.PubMedCrossRefGoogle Scholar
  26. 26.
    Imazano Y, Takebayashi Y, Nishiyama K, Akiba S, Miyadera K, Yamada Y, et al. Correlation between thymidine phosphorylase expression and prognosis in human renal cell carcinoma. J Clin Oncol. 1997;15:2570–8.PubMedGoogle Scholar
  27. 27.
    Egger M, Zellweger-Zahner T, Schneider M, Junker C, Lengeler C, Antes G. Language bias in randomised controlled trials published in English and German. Lancet. 1997;350:326–9.PubMedCrossRefGoogle Scholar
  28. 28.
    Zhu S, Zhang H, Xie L, Chen J, Niu Y. Risk factors and prevention of inguinal hernia after radical prostatectomy: a systematic review and meta-analysis. J Urol. 2013;189:884–90.PubMedCrossRefGoogle Scholar
  29. 29.
    Altman DG, Riley RD. Primer: an evidence-based approach to prognostic markers. Nat Clin Pract Oncol. 2005;2:466–72.PubMedCrossRefGoogle Scholar
  30. 30.
    Goebell PJ, Groshen S, Schmitz-Drager BJ, Sylvester R, Kogevinas M, Malats N, et al. The international bladder cancer bank: proposal for a new study concept. Urol Oncol. 2004;22:277–84.PubMedCrossRefGoogle Scholar
  31. 31.
    Baltaci S, Orhan D, Gogus C, Filiz E, Tulunay O, Gogus O: Thrombospondin-1, vascular endothelial growth factor expression and microvessel density in renal cell carcinoma and their relationship with multifocality. Eur Urol 2003;44:76–81, 81.Google Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2013

Authors and Affiliations

  • Bing Zhang
    • 1
    • 3
  • Hong Ji
    • 2
  • Dongliang Yan
    • 3
  • Shaoqing Liu
    • 3
  • Benkang Shi
    • 1
  1. 1.Department of Urology, Qilu HospitalShandong UniversityJinanChina
  2. 2.Department of pathologyBinzhou Medical University HospitalBinzhouChina
  3. 3.Department of UrologyBinzhou Medical University HospitalBinzhouChina

Personalised recommendations