Correlation of Microvessel Density with Nuclear Pleomorphism, Mitotic Count and Vascular Invasion in Breast and Prostate Cancers at Preclinical and Clinical Levels

  • Published : 2013.01.31


Background: Tumor angiogenesis correlates with recurrence and appears to be a prognostic factor for both breast and prostate cancers. In the present study, we aimed to investigate the correlation of microvessel density (MVD), a measure of angiogenesis, with nuclear pleomorphism, mitotic count, and vascular invasion in breast and prostate cancers at preclinical and clinical levels. Methods: Samples from xenograft tumors of luminal B breast cancer and prostate adenocarcinoma, established by BT-474 and PC-3 cell lines, respectively, and commensurate human paraffin-embedded blocks were obtained. To determine MVD, specimens were immunostained for CD-34. Nuclear pleomorphism, mitotic count, and vascular invasion were determined using hematoxylin and eosin (H&E)-stained slides. Results: MVD showed significant correlations with nuclear pleomorphism (r=0.68, P=0.03) and vascular invasion (r=0.77, P=0.009) in breast cancer. In prostate cancer, MVD was significantly correlated with nuclear pleomorphism (r=0.75, P=0.013) and mitotic count (r=0.75, P=0.012). In the breast cancer xenograft model, a significant correlation was observed between MVD and vascular invasion (r=0.87, P=0.011). In the prostate cancer xenograft model, MVD was significantly correlated with all three parameters (nuclear pleomorphism, r=0.95, P=0.001; mitotic count, r=0.91, P=0.001; and vascular invasion, r=0.79, P=0.017; respectively). Conclusions: Our results demonstrate that MVD is correlated with nuclear pleomorphism, mitotic count, and vascular invasion at both preclinical and clinical levels. This study therefore supports the predictive value of MVD in breast and prostate cancers.


  1. Siegel R, Naishadham D, Jemal A (2012). Cancer statistics for Hispanics/Latinos, 2012. CA Cancer J Clin, 62, 10-29.
  2. Song YJ, Shin SH, Cho JS, et al (2011). The role of lymphovascular invasion as a prognostic factor in patients with lymph nodepositive operable invasive breast cancer. J Breast Cancer, 14, 198-203.
  3. Tezuka K, Onoda N, Takashima T, et al (2007). Prognostic significance of lymphovascular invasion diagnosed by lymphatic endothelium immunostaining in breast cancer patients. Oncol Rep, 17, 997-1003.
  4. Tomayko MM, Reynolds CP (1989). Determination of subcutaneous tumor size in athymic (nude) mice. Cancer Chemother Pharmacol, 24, 148-54.
  5. Tse GM, Lui PC, Lee CS, et al (2004). Stromal expression of vascular endothelial growth factor correlates with tumor grade and microvessel density in mammary phyllodes tumors: a multicenter study of 185 cases. Hum Pathol, 35, 1053-7.
  6. Uzzan B, Nicolas P, Cucherat M, Perret G Y (2004). Microvessel density as a prognostic factor in women with breast cancer: a systematic review of the literature and meta-analysis. Cancer Res, 64, 2941-55.
  7. Yamamoto S, Kawakami S, Yonese J, et al (2008). Lymphovascular invasion is an independent predictor of prostate-specific antigen failure after radical prostatectomy in patients with pT3aN0 prostate cancer. Int J Urol, 15, 895-9.
  8. Yao L, Zhou LQ, He ZS, et al (2010). Clinical study on intermittent hormonal therapy for patients with prostate cancer. Beijing Da Xue Xue Bao, 42, 396-9.
  9. Zerbini G, Lorenzi M, Palili A (2008). Tumor Angiogenesis. N Engl J Med, 7, 359-63.
  10. Lee JS, Kim HS, Jung JJ, et al (2001). Correlation between angiogenesis, apoptosis and cell proliferation in invasive ductal carcinoma of the breast and their relation to tumor behavior. Anal Quant Cytol Histol, 23, 161-8.
  11. Li WW, Li VW, Hutnik M, Chiou AS (2012). Tumor angiogenesis as a target for dietary cancer prevention. J Oncol, 879623
  12. Li YJ, Deng YJ, Zhang XL (2009). Evaluation of angiogenesis in the tumorigenesis and progression of breast cancer. Zhonghua Wai Ke Za Zhi, 47, 519-22.
  13. Luporsi E, Andre F, Spyratos F, et al (2011). Ki-67: level of evidence and methodological considerations for its role in the clinical management of breast cancer: analytical and critical review. Breast Cancer Res Treat, 132, 895-915.
  14. Malvezzi M, Bertuccio P, Levi F, La Vecchia C, Negri E, (2012). European cancer mortality predictions for the year. Ann Oncol, 23, 1044-52.
  15. Marrinucci D, Bethel K, Bruce RH, et al (2007). Case study of the morphologic variation of circulating tumor cells. Hum Pathol, 38, 514-9.
  16. Medina VA, Brenzoni PG, Lamas DJ, et al (2011). Role of histamine H4 receptor in breast cancer cell proliferation. Front Biosci (Elite Ed), 1, 1042-60.
  17. Miyamoto S, Ito K, Miyakubo M, et al (2012). Impact of pretreatment factors, biopsy Gleason grade volume indices and post-treatment nadir PSA on overall survival in patients with metastatic prostate cancer treated with step-up hormonal therapy. Prostate Cancer Prostatic Dis, 15, 75-86.
  18. Moise M, Motoc A, Raducan A, Raducan S, Niculescu M (2011). Human epidermal growth factor receptor 2 (HER2/neu) supraexpression in the mammary tumors. Rom J Morphol Embryol, 52, 1101-5.
  19. Ng J, Mahmud A, Bass B, Brundage M (2012). Prognostic significance of lymphovascular invasion in radical prostatectomy specimens. BJU Int, In press.
  20. Rakha EA, Martin S, Lee AH, et al (2011). The prognostic significance of lymphovascular invasion in invasive breast carcinoma. Cancer, 118, 3670-80.
  21. Rykala J, Przybylowska K, Majsterek I, et al (2011). Angiogenesis markers quantification in breast cancer and their correlation with clinicopathological prognostic variables. Pathol Oncol Res, 17, 809-17.
  22. Sakurai T, Kudo M (2011). Signaling pathways governing tumor angiogenesis. Oncology, 81, 24-9.
  23. Shpitz B, Bomstin Y, Sternberg A, et al (2000). Angiogenesis, p53, and c-erbB-2 immunoreactivity and clinicopathological features in male breast cancer. J Surg Oncol, 75, 252-7.<252::AID-JSO5>3.0.CO;2-2
  24. Kim HJ, Lee YS, Won EH, et al (2011). Expression of resistin in the prostate and its stimulatory effect on prostate cancer cell proliferation. BJU Int, 108, 77-83.
  25. Koukourakis MI, Manolas C, Minopoulos G, Giatromanolaki A, Sivridis E (2003). Angiogenesis relates to estrogen receptor negativity, c-erbB-2 overexpression and early relaps in node-negative ductal carcinoma of the breast. Int J Surg Pathol, 11, 29-34.
  26. Courtneidge SA (2012). Cell migration and invasion in human disease: the Tks adaptor proteins. Bichem Soc Trans, 40, 129-32.
  27. Fichtner I, Monks A, Hose C, et al (2004). The experimental antitumor agents Phortress and doxorubicin are equiactive against human-derived breast carcinoma xenograft models. Breast Cancer Res Treat, 87, 97-107.
  28. Gordon MS, Mendelson DS, Kato G (2010). Tumor angiogenesis and novel antiangiogenic strategies. Int J Cancer, 126, 1777-87.
  29. Jonsson G, Staaf J, Olsson E, et al (2007). High-resolution genomic profiles of breast cancer cell lines assessed by tiling BAC array comparative genomic hybridization. Genes Chromosomes Cancer, 46, 543-58.
  30. Kerbel RS (2008). Tumor Angiogenesis. N Engl J Med, 358, 2039-49

Cited by

  1. Effect of Lymphangiogenesis and Lymphovascular Invasion on the Survival Pattern of Breast Cancer Patients vol.15, pp.15, 2014,
  2. Overexpression of HER-2/neu in Patients with Prostatic Adenocarcinoma vol.15, pp.15, 2014,
  3. Microvessel Density as a Prognostic Factor in Ovarian Cancer: a Systematic Review and Meta-analysis vol.16, pp.3, 2015,
  4. Platinum-Based Drugs Differentially Affect the Ultrastructure of Breast Cancer Cell Types vol.2017, pp.2314-6141, 2017,
  5. Tumor vascularity in prostate cancer: an update on circulating endothelial cells and platelets as noninvasive biomarkers vol.7, pp.6, 2013,
  6. Prognostic factors in patients with recurrent or metastatic retroperitoneal leiomyosarcoma vol.11, pp.12, 2015,
  7. Salivary levels and immunohistochemical expression of selected angiogenic factors in benign and malignant parotid gland tumours pp.1436-3771, 2018,