Pathology & Oncology Research

, Volume 24, Issue 3, pp 515–524 | Cite as

Distribution of Vascular Patterns in Different Subtypes of Renal Cell Carcinoma. A Morphometric Study in Two Distinct Types of Blood Vessels

  • Amparo Ruiz-SauríEmail author
  • V. García-Bustos
  • E. Granero
  • S. Cuesta
  • M. A. Sales
  • V. Marcos
  • A. Llombart-Bosch
Original Article


To analyze the presence of mature and immature vessels as a prognostic factor in patients with renal cell carcinoma and propose a classification of renal cancer tumor blood vessels according to morphometric parameters. Tissue samples were obtained from 121 renal cell carcinoma patients who underwent radical nephrectomy. Staining with CD31 and CD34 was used to differentiate between immature (CD31+) and mature (CD34+) blood vessels. We quantified the microvascular density, microvascular area and different morphometric parameters: maximum diameter, minimum diameter, major axis, minor axis, perimeter, radius ratio and roundness. We found that the microvascular density was higher in CD31+ than CD34+ vessels, but CD34+ vessels were larger than CD31+ vessels, as well as being strongly correlated with the ISUP tumor grade. We also identified four vascular patterns: pseudoacinar, fascicular, reticular and diffuse. Pseudoacinar and fascicular patterns were more frequent in clear cell renal cell carcinoma (37.62 and 35.64% respectively), followed by reticular pattern (21.78%), while in chromophobe tumors the reticular pattern predominated (90%). The isolated pattern was present in all papillary tumors (100%). In healthy renal tissue, the pseudoacinar and isolated patterns were differentially found in the renal cortex and medulla respectively. We defined four distinct vascular patterns significantly related with the ISUP tumor grade in renal cell carcinomas. Further studies in larger series are needed in order to validate these results. Analysis of both mature and immature vessels (CD34+ and CD31+) provides additional information when evaluating microvascular density.


Clear cell renal cell carcinoma Papillary renal cell carcinoma Chromophobe renal cell carcinoma Microvascular density Microvascular area Morphometry CD31 CD34 Renal vascular patterns 


Compliance with Ethical Standards

Conflict of Interest

We declare no conflict of interest.


  1. 1.
    Zhang B, Ji H, Yan D, Liu S, Shi B (2014) Lack of association of microvessel density with prognosis of renal cell carcinoma: evidence from meta-analysis. Tumor Biol 35(3):2769–2776CrossRefGoogle Scholar
  2. 2.
    Döme B, Hendrix MJC, Paku S, Tóvári J, Tímár J (2007) Alternative vascularization mechanisms in cancer. Am J Pathol 170(1):1–15CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Srigley JR, Delahunt B (2009) Uncommon and recently described renal carcinomas. Mod Pathol 22(Suppl 2):S2–23CrossRefPubMedGoogle Scholar
  4. 4.
    Murphy WM, Grignon DG, Perlman EJ (2004) Tumors of the kidney, bladder, and related urinary structures. American Registry of Pathology, WashingtonGoogle Scholar
  5. 5.
    Delahunt B, Eble JN, McCredie MR, Bethwaite PB, Stewart JH, Bilous AM (2001) Morphologic typing of papillary renal cell carcinoma: comparison of growth kinetics and patient survival in 66 cases. Hum Pathol 32:590–595CrossRefPubMedGoogle Scholar
  6. 6.
    Storkel S, Eble JN, Adlakha K et al (1997) Classification of renal carcinoma. Cancer 80:987–989CrossRefPubMedGoogle Scholar
  7. 7.
    Thoenes W, Storkel S, Rompelt HJ, Moll R, Baum HP, Werner S (1988) Chromophobe cell renal carcinoma and its variants. A report in 32 cases. J. Pathol 155:277–287CrossRefGoogle Scholar
  8. 8.
    Hlatky L, Hahnfeldt P, Folkman J (2002) Clinical application of antiangiogenic therapy: microvessel density, what it does and doesn’t tell us. J Nat Cancer Inst 94:883–893CrossRefPubMedGoogle Scholar
  9. 9.
    Grizzi F, Colombo P, Barbieri B et al (2001) Microscopic analysis and significance of vascular architectural complexity in renal cell carcinoma. Clin Cancer Res 7:3305–3307PubMedGoogle Scholar
  10. 10.
    Weidner N, Semple JP, Welch WR, Folkman J (1991) Tumor angiogenesis and metastasis: correlation in invasive breast carcinoma. N Engl J Med 324:1–8CrossRefPubMedGoogle Scholar
  11. 11.
    Grizzi F, Ceva-Grimaldi G, Dioguardi N (2001a) Fractal geometry: a useful tool for quantifying irregular lesions in human liver biopsy specimens. Ital J Anat Embryol 106:337–346PubMedGoogle Scholar
  12. 12.
    Kovacs G, Akhtar M, Beckwith BJ et al (1997) The Heidelberg classification of renal cell tumours. J Pathol 80:992–993Google Scholar
  13. 13.
    Ljungberg B, Bensalah K, Canfield S, Dabestani S, Hofmann F, Hora M, et al (20015). EAU Guidelines on Renal Cell Carcinoma 2014 Update. Eur Urol 67(5): 913–924Google Scholar
  14. 14.
    Delahunt B, Srigley JR, Montironi R, Egevad L (2014) Advances in renal neoplasia: recommendations from the 2012 International Society of Urological Pathology Consensus Conference. Urology 83(5):969–974CrossRefPubMedGoogle Scholar
  15. 15.
    Poblet E, González-Palacios F, Jimenez FJ (1996) Different immunoreactivity of endotelial markers in well and poorly differentiated areas of angiosarcomas. Virchows Arch 428:217–221PubMedGoogle Scholar
  16. 16.
    Yilmazer D, Han U, Onal B (2007) A comparison of the vascular density of VEGF expression with microvascular density determined with CD34 and CD31 staining and conventional prognostic markers in renal cell carcinoma. Int Urol Nephrol 39:691–698CrossRefPubMedGoogle Scholar
  17. 17.
    Meert AP, Paesmans M, Martin B, Delmotte P, Berghmans T, Verdebout JM, Lafitte JJ, Mascaux C, Sculier JP (2002) The role of microvessel density on the survival of patients with lung cancer: a systematic review of the literature with meta-analysis. Br J Cancer 87:694–701CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Uzzan B, Nicolas P, Cucherat M, Perret GY (2004) Microvessel density as a prognostic factor in women with breast cancer: a systematic review of the literature and meta-analysis. Cancer Res 64:2941–2955CrossRefPubMedGoogle Scholar
  19. 19.
    Des Guetz G, Uzzan B, Nicolas P, Cucherat M, Morere JF, Benamouzig R, Breau JL, Perret GY (2006) Microvessel density and VEGF expression are prognostic factors in colorectal cancer. Meta-analysis of the literature. Br J Cancer 94:1823–1832CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Ruiz-Saurí A, Valencia-Villa G, Romanenko A, Pérez J, García R, García H, Benavent J, Sancho-Tello M, Carda C, Llombart-Bosch A (2016) Influence of exposure to chronic persistent low-dose ionizing radiation on the tumor biology of clear-cell renal-cell carcinoma. An Immunohistochemical and morphometric study of angiogenesis and vascular related factors. Pathol Oncol Res 22(4):807–815CrossRefPubMedGoogle Scholar
  21. 21.
    Joo HJ, Oh DK, Kim YS, Lee KB, Kim SJ (2004) Increased expression of caveolin-1 and microvessel density correlates with metastasis and poor prognosis in clear cell renal cell carcinoma. BJU Int 93:291–296CrossRefPubMedGoogle Scholar
  22. 22.
    Nativ O, Sabo E, Reiss A, Wald M, Madjar S, Moskovitz B (1998) Clinical significance of tumor angiogenesis in patients with localized renal cell carcinoma. Urology 51:693–696CrossRefPubMedGoogle Scholar
  23. 23.
    Yoshino S, Kato M, Okada K (1995) Prognostic significance of microvessel count in low stage renal cell carcinoma. Int J Urol 2:156–160CrossRefPubMedGoogle Scholar
  24. 24.
    MacLennan GT, Bostwick DG (1995) Microvessel density in renal cell carcinoma: lack of prognostic significance. Urology 46:27–30CrossRefPubMedGoogle Scholar
  25. 25.
    Minardi D, Lucarini G, Mazzucchelli R, Milanese G, Natali D, Galosi AB, Montironi R, Biagini G, Muzzonigro G (2005) Prognostic role of Fuhrman grade and vascular endothelial growth factor in pT1a clear cell carcinoma in partial nephrectomy specimens. J Urol 174:1208–1212CrossRefPubMedGoogle Scholar
  26. 26.
    Anastassiou G, Duensing S, Steinhoff G, Zorn U, Grosse J, Dallmann I, Kirchner H, Ganser A, Atzpodien J (1996) Platelet endothelial cell adhesion molecule-1 (PECAM-1): a potential prognostic marker involved in leukocyte infiltration of renal cell carcinoma. Oncology 53:127–132CrossRefPubMedGoogle Scholar
  27. 27.
    Imao T, Egawa M, Takashima H, Koshida K, Namiki M (2004) Inverse correlation of microvessel density with metastasis and prognosis in renal cell carcinoma. Int J Urol 11:948–953CrossRefPubMedGoogle Scholar
  28. 28.
    Rioux-Leclercq N, Epstein JI, Bansard JY, Turlin B, Patard JJ, Manunta A, Chan T, Ramee MP, Lobel B, Moulinoux JP (2001) Clinical significance of cell proliferation, microvessel density, and CD44 adhesion molecule expression in renal cell carcinoma. Hum Pathol 32:1209–1215CrossRefPubMedGoogle Scholar
  29. 29.
    Sabo E, Boltenko A, Sova Y, Stein A, Kleinhaus S, Resnick MB (2001) Microscopic analysis and significance of vascular architectural complexity in renal cell carcinoma. Clin Cancer Res 7:533–537PubMedGoogle Scholar
  30. 30.
    Schraml P, Struckmann K, Hatz F, Sonnet S, Kully C, Gasser T, Sauter G, Mihatsch MJ, Moch H (2002) VHL mutations and their correlation with tumour cell proliferation, microvessel density, and patient prognosis in clear cell renal cell carcinoma. J Pathol 196:186–193CrossRefPubMedGoogle Scholar
  31. 31.
    Cheng S-H, Liu J-M, Liu Q-Y, Luo D-Y, Liao B-.H, Li H, Wang K-J (2014). Prognostic role of microvessel density in patients with renal cell carcinoma: a meta-analysis. Int J Clin Exp Pathol 7(9): 5855–5863Google Scholar
  32. 32.
    Ferician O, Cimpean AM, Ceasu AM, Dema A, Raica M, Cumpanas A (2016) Heterogeneous vascular patterns in renal cell carcinomas. Pol J Pathol 67(1):46–53CrossRefPubMedGoogle Scholar
  33. 33.
    Joshi S, Singh AR, Durden DL (2015) Pan-PI-3 kinase inhibitor SF 1126 shows antitumor and antiangiogenic activity in renal cell carcinoma. Cancer Chemother Pharmacol 75:595–608CrossRefPubMedGoogle Scholar
  34. 34.
    Schirner M, Hoffmann J, Menrad A, Schneider MR (1998) Antiangiogenic chemotherapeutic agents: characterization in comparison to their tumor growth inhibition in human renal cell carcinoma models. Clin Cancer Res 4:1331–1336PubMedGoogle Scholar
  35. 35.
    Travnicek I, Branzovsky H, Kalusova K, Hess O, Holubec L, Pele KB, Ürge T, Hora M (2015) Tissue biomarkers in predicting response to sunitinib treatment of metastatic renal cell carcinoma. Anticancer Res 35:5661–5666PubMedGoogle Scholar
  36. 36.
    Porta C, Giglione P, Liguigli W, Paglino C (2015) Dovitinib (CHIR258, TKI258): structure, development and preclinical and clinical activity. Future Oncol 11:39–50CrossRefPubMedGoogle Scholar
  37. 37.
    Okoń K, Kawa R (2008) Microvascular network in renal carcinomas. Quantitative and tissue microarray immunohistochemical study. Pol J Pathol 59:107–115PubMedGoogle Scholar
  38. 38.
    Tinini T, Rossi F, Claudio PP (2003) Molecular basis of angiogenesis and cancer. Oncogene 22:6549–6556CrossRefGoogle Scholar
  39. 39.
    Eberhard A, Kahlert S, Goede V, Hemmerlein B, Plate KH, Augustin HG (2000) Heterogeneity of angiogenesis and blood vessel maturation in human tumors: implications for antiangiogenic tumor therapies. Cancer Res 60:1388–1393PubMedGoogle Scholar

Copyright information

© Arányi Lajos Foundation 2017

Authors and Affiliations

  • Amparo Ruiz-Saurí
    • 1
    • 2
    Email author
  • V. García-Bustos
    • 1
  • E. Granero
    • 1
  • S. Cuesta
    • 1
  • M. A. Sales
    • 3
  • V. Marcos
    • 1
  • A. Llombart-Bosch
    • 1
  1. 1.Department of Pathology, Faculty of Medicine and OdontologyUniversity of ValenciaValenciaSpain
  2. 2.INCLIVA, Biomedical Research InstituteValenciaSpain
  3. 3.Department of PathologyUniversity Clinical HospitalValenciaSpain

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