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Prognostic value of microvessel density in prostate cancer: a tissue microarray study

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Abstract

Purpose

Angiogenesis is an important part in tumor progression and intratumoral microvessel density (MVD) has proven a prognostic factor in several solid tumors. However, its value in prostate cancer is still unclear, especially in small biopsy samples. We evaluated the prognostic potential of MVD in a large, homogeneous cohort of prostate cancers and its correlation with other pathologic parameters.

Methods

We used a tissue microarray (TMA) containing samples of 3,261 prostatectomy specimens from patients with prostate cancer. MVD was determined by counting vessels in a blinded fashion after immunohistochemical staining with an antibody against CD31. The results were compared with pre- and postoperative clinical and pathological parameters and clinical follow-up data.

Results

MVD was higher in TMA spots containing cancer as compared to benign tissue (P < 0.001). There was no significant correlation of MVD with preoperative parameters, but with pathological T-classification and Gleason score (P < 0.001, each) of the prostatectomy specimens. Furthermore, a higher MVD correlated with tumor location in the peripheral zone (P = 0.01). Follow-up data were available for 1,521 patients. In a univariable analysis, an MVD of ≥36 per spot was a significant predictor of PSA recurrence after radical prostatectomy (P = 0.03). However, it failed to provide an independent prognostic factor when combined with standard predictors in a multivariable analysis.

Conclusions

MVD in prostate cancer is closely related to other factors contributing to tumor aggressiveness. However, the implementation of this parameter into routinely performed pathological reports does not seem to be warranted.

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References

  1. Gimbrone MA Jr, Leapman SB, Cotran RS, Folkman J (1972) Tumor dormancy in vivo by prevention of neovascularization. J Exp Med 136:261–276

    Article  PubMed  Google Scholar 

  2. Weidner N (1995) Intratumor microvessel density as a prognostic factor in cancer. Am J Pathol 147:9–19

    CAS  PubMed  Google Scholar 

  3. Weidner N (1998) Tumor vascularity as a prognostic factor in cancer patients: the evidence continues to grow. J Pathol 184:119–122

    Article  CAS  PubMed  Google Scholar 

  4. Fox SB, Gatter KC, Harris AL (1996) Tumour angiogenesis. J Pathol 179:232–237

    Article  CAS  PubMed  Google Scholar 

  5. Weidner N, Carroll PR, Flax J, Blumenfeld W, Folkman J (1993) Tumor angiogenesis correlates with metastasis in invasive prostate carcinoma. Am J Pathol 143:401–409

    CAS  PubMed  Google Scholar 

  6. Silberman MA, Partin AW, Veltri RW, Epstein JI (1997) Tumor angiogenesis correlates with progression after radical prostatectomy but not with pathologic stage in Gleason sum 5 to 7 adenocarcinoma of the prostate. Cancer 79:772–779

    Article  CAS  PubMed  Google Scholar 

  7. Hall MC, Troncoso P, Pollack A, Zhau HY, Zagars GK, Chung LW, Von Eschenbach AC (1994) Significance of tumor angiogenesis in clinically localized prostate carcinoma treated with external beam radiotherapy. Urology 44:869–875

    Article  CAS  PubMed  Google Scholar 

  8. Concato J, Jain D, Li WW, Risch HA, Uchio EM, Wells CK (2007) Molecular markers and mortality in prostate cancer. BJU Int 100:1259–1263

    Article  PubMed  Google Scholar 

  9. Revelos K, Petraki C, Scorilas A, Stefanakis S, Malovrouvas D, Alevizopoulos N, Kanellis G, Halapas A, Koutsilieris M (2007) Correlation of androgen receptor status, neuroendocrine differentiation and angiogenesis with time-to-biochemical failure after radical prostatectomy in clinically localized prostate cancer. Anticancer Res 27:3651–3660

    PubMed  Google Scholar 

  10. Mehta R, Kyshtoobayeva A, Kurosaki T, Small EJ, Kim H, Stroup R, McLaren CE, Li KT, Fruehauf JP (2001) Independent association of angiogenesis index with outcome in prostate cancer. Clin Cancer Res 7:81–88

    CAS  PubMed  Google Scholar 

  11. Strohmeyer D, Rossing C, Strauss F, Bauerfeind A, Kaufmann O, Loening S (2000) Tumor angiogenesis is associated with progression after radical prostatectomy in pT2/pT3 prostate cancer. Prostate 42:26–33

    Article  CAS  PubMed  Google Scholar 

  12. Concato J, Jain D, Uchio E, Risch H, Li WW, Wells CK (2009) Molecular markers and death from prostate cancer. Ann Intern Med 150:595–603

    PubMed  Google Scholar 

  13. Gettman MT, Bergstralh EJ, Blute M, Zincke H, Bostwick DG (1998) Prediction of patient outcome in pathologic stage T2 adenocarcinoma of the prostate: lack of significance for microvessel density analysis. Urology 51:79–85

    Article  CAS  PubMed  Google Scholar 

  14. Gettman MT, Pacelli A, Slezak J, Bergstralh EJ, Blute M, Zincke H, Bostwick DG (1999) Role of microvessel density in predicting recurrence in pathologic stage T3 prostatic adenocarcinoma. Urology 54:479–485

    Article  CAS  PubMed  Google Scholar 

  15. Rubin MA, Buyyounouski M, Bagiella E, Sharir S, Neugut A, Benson M, de-la-Taille A, Katz AE, Olsson CA, Ennis RD (1999) Microvessel density in prostate cancer: lack of correlation with tumor grade, pathologic stage, and clinical outcome. Urology 53:542–547

    Article  CAS  PubMed  Google Scholar 

  16. Di LG, De PS, Autorino R, De Laurentiis M, Mignogna C, D’Armiento M, Tortora G, De RG, D’Armiento M, De SM, Bianco AR, D’Armiento FP (2005) Expression of biomarkers modulating prostate cancer progression: implications in the treatment of the disease. Prostate Cancer Prostatic Dis 8:54–59

    Article  Google Scholar 

  17. Offersen BV, Borre M, Sorensen FB, Overgaard J (2002) Comparison of methods of microvascular staining and quantification in prostate carcinoma: relevance to prognosis. APMIS 110:177–185

    Article  PubMed  Google Scholar 

  18. Bostwick DG, Wheeler TM, Blute M, Barrett DM, MacLennan GT, Sebo TJ, Scardino PT, Humphrey PA, Hudson MA, Fradet Y, Miller GJ, Crawford ED, Blumenstein BA, Mahran HE, Miles BJ (1996) Optimized microvessel density analysis improves prediction of cancer stage from prostate needle biopsies. Urology 48:47–57

    Article  CAS  PubMed  Google Scholar 

  19. Bubendorf L, Nocito A, Moch H, Sauter G (2001) Tissue microarray (TMA) technology: miniaturized pathology archives for high-throughput in situ studies. J Pathol 195:72–79

    Article  CAS  PubMed  Google Scholar 

  20. Torhorst J, Bucher C, Kononen J, Haas P, Zuber M, Köchli OR, Mross F, Dieterich H, Moch H, Mihatsch M, Kallioniemi O-P, Sauter G (2001) Tissue microarrays for rapid linking of molecular changes to clinical endpoints. Am J Pathol 159:2249–2256

    CAS  PubMed  Google Scholar 

  21. Rogatsch H, Hittmair A, Reissigl A, Mikuz G, Feichtinger H (1997) Microvessel density in core biopsies of prostatic adenocarcinoma: a stage predictor? J Pathol 182:205–210

    Article  CAS  PubMed  Google Scholar 

  22. Hsu S-M, Raine L, Fanger H (1981) Use of avidin–biotin-peroxidase complex (ABC) in immunoperoxidase techniques: a comparison between ABC and unlabeled antibody (PAP) procedures. J Histochem Cytochem 29:577–580

    CAS  PubMed  Google Scholar 

  23. Mazumdar M, Glassman JR (2000) Categorizing a prognostic variable: review of methods, code for easy implementation and applications to decision-making about cancer treatments. Stat Med 19:113–132

    Article  CAS  PubMed  Google Scholar 

  24. Harrell FE Jr, Lee KL, Mark DB (1996) Multivariable prognostic models: issues in developing models, evaluating assumptions and adequacy, and measuring and reducing errors. Stat Med 15:361–387

    Article  PubMed  Google Scholar 

  25. Brawer MK, Deering RE, Brown M, Preston SD, Bigler SA (1994) Predictors of pathologic stage in prostatic carcinoma. The role of neovascularity. Cancer 73:678–687

    Article  CAS  PubMed  Google Scholar 

  26. Bono AV, Celato N, Cova V, Salvadore M, Chinetti S, Novario R (2002) Microvessel density in prostate carcinoma. Prostate Cancer Prostatic Dis 5:123–127

    Article  CAS  PubMed  Google Scholar 

  27. Borre M, Offersen BV, Nerstrom B, Overgaard J (1998) Microvessel density predicts survival in prostate cancer patients subjected to watchful waiting. Br J Cancer 78:940–944

    CAS  PubMed  Google Scholar 

  28. Erbersdobler A, Augustin H, Schlomm T, Henke RP (2004) Prostate cancers in the transition zone. Part 1. Pathological aspects. BJU Int 94:1221–1225

    Article  PubMed  Google Scholar 

  29. Erbersdobler A, Fritz H, Schnöger S, Graefen M, Hammerer P, Huland H, Henke R-P (2002) Tumour grade, proliferation, apoptosis, microvessel density, p53, and bcl-2 in prostate cancers: differences between tumours located in the transition zone and in the peripheral zone. Eur Urol 41:40–46

    Article  CAS  PubMed  Google Scholar 

  30. Noguchi M, Stamey TA, Neal JE, Yemoto CE (2000) An analysis of 148 consecutive transition zone cancers: clinical and histological characteristics. J Urol 163:1751–1755

    Article  CAS  PubMed  Google Scholar 

  31. Bostwick DG, Grignon DJ, Hammond ME, Amin MB, Cohen M, Crawford D, Gospadarowicz M, Kaplan RS, Miller DS, Montironi R, Pajak TF, Pollack A, Srigley JR, Yarbro JW (2000) Prognostic factors in prostate cancer. College of American Pathologists Consensus Statement 1999. Arch Pathol Lab Med 124:995–1000

    CAS  PubMed  Google Scholar 

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Correspondence to Andreas Erbersdobler.

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A. Erbersdobler and H. Isbarn contributed equally to this work.

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Erbersdobler, A., Isbarn, H., Dix, K. et al. Prognostic value of microvessel density in prostate cancer: a tissue microarray study. World J Urol 28, 687–692 (2010). https://doi.org/10.1007/s00345-009-0471-4

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  • DOI: https://doi.org/10.1007/s00345-009-0471-4

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