Measuring Intratumoral Microvessel Density

  • Noel Weidner
Part of the NATO ASI Series book series (NSSA, volume 298)


Although Brem et al. (Brem, Cotran, Folkman, 1972) were among the first to suggest that the intensity of intratumoral angiogenesis may correlate with tumor grade and aggressiveness, the first clear-cut evidence that tumor angiogenesis in a human solid tumor could predict the probability of metastasis was reported for cutaneous melanoma. Srivastava et al. (Srivastava, Laidler, Davies, Horgan, Hughes, 1988) studied the vascularity of 20 intermediate thickness skin melanomas. Vessels were highlighted and the stained histologic sections analyzed with an image analysis system. The 10 cases that developed metastases had a vascular area at the tumor base that was more than twice that seen in the 10 cases without metastases (p=0.025).


Breast Carcinoma Tumor Angiogenesis Cutaneous Melanoma Microvessel Density Invasive Breast Carcinoma 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Abulafia, O., Triest, W. E., Sherer, D. M., Hansen, C. C., Ghezzi, F., 1995, Angiogenesis in endometrial hyperplasia and stage I endometrial carcinoma, Obstet. Gynecol.86:479–485.PubMedGoogle Scholar
  2. Albo, D., Granick, M. S., Jhala, N., Atkinson, B., Solomon, M. P., 1994, The relationship of angiogenesis to biological activity in human squamous cell carcinomas of the head and neck, Ann. Plast. Surg. 32:588–594.PubMedCrossRefGoogle Scholar
  3. Alcalde, R. E., Shintani, S., Yoshihama, Y., Matsumura, T., 1995, Cell proliferation and tumor angiogenesis in oral squamous cell carcinomas, Anticancer Res. 15:1417–1422.PubMedGoogle Scholar
  4. Angeletti, C. A., Lucchi, M., Fontanini, G., Mussi, A., Chella, A., Ribechini, A., Vignati, S., Bevilacqua, G., 1996, Prognostic significance of tumoral angiogenesis in completely resected late stage lung carcinoma (stage IIIA-N2). Impact of adjuvant therapies in a subset of patients at high risk of recurrence, Cancer 78:409–15.PubMedCrossRefGoogle Scholar
  5. Axelsson, K., Ljung, B. M. E., Moore, D. H., Thor, A. D., Chew, K. L., Edgerton, S. M., Smith, H. S., Mayall, B. H., 1995, Tumor angiogenesis as a prognostic assay for invasive ductal carcinoma, J. Natl. Cancer Inst. 87:997–1008.PubMedCrossRefGoogle Scholar
  6. Barbareschi, M., Gasparini, G., Weidner, N., Morelli, L., Forti, S., Eccher, C., Fina, P., Leonardi, E., Mauri, F., Bevilacqua, P., Dalla Palma, P., 1995, Microvessel density quantification in breast carcinomas: assessment by manual vs. a computer-assisted image analysis system, Appl. Immunohistochem. 3:75–84.Google Scholar
  7. Barnhill, R. L., Levy, M. A., 1993, Regressing thin cutaneous malignant melanomas (<1.0 mm) are associated with angiogenesis, Am. J. Pathol. 143:99–104.PubMedGoogle Scholar
  8. Barnhill R. L., Busam, K. J., Berwick, M., Blessing, K., Cochran, A. J., Elder, D. E., Fandrey, K., Daraoli, T., White, W.L., 1994, Tumor vascularity is not a prognostic factor for cutaneous melanoma [letter], Lancet 344:1237–1238.PubMedCrossRefGoogle Scholar
  9. Bevilacqua, P., Barbareschi, M., Verderio, P., Boracchi, P., Caffo, O., Dalla Palma, P., Meli S., Weidner, N., Gasparini, G., 1995, Prognostic value of intratumoral microvessel density, a measure of tumor angiogenesis, in node-negative breast carcinoma — results of a multiparametric study, Breast Cancer Res. Treat. 36:205–217.PubMedCrossRefGoogle Scholar
  10. Bochner, B. H., Cote, R. J., Weidner, N., Groshen, S., Chen, S-C., Skinner, D. G., Nichols, P. W., 1995, Angiogenesis in bladder cancer: relationship between microvessel density and tumor prognosi s, J. Natl. Cancer Inst. 87:1603–1612.PubMedCrossRefGoogle Scholar
  11. Bosari, S., Lee, A. K., DeLellis, R. A., Wiley, B. D., Heatley, G.J., Silverman, M. L., 1992, Microvessel quantitation and prognosis in invasive breast carcinoma, Hum. Pathol 23:755–761.PubMedCrossRefGoogle Scholar
  12. Brawer, M. K., Deering, R. E., Brown, M., Preston, S. D., Bigler, S. A. 1994, Predictors of pathologic stage in prostate carcinoma, Cancer 73:678–687.PubMedCrossRefGoogle Scholar
  13. Brem, S., Cotran, R., Folkman, J., 1972, Tumor angiogenesis: a quantitative method for histologic grading, J. Natl. Cancer Inst. 48:347–356.PubMedGoogle Scholar
  14. Bremer, G. L., Tiebosch, A. T. M. G., van der Putten, H. W. H. M., Schouten, H. J. A., de Haan, J., Arends, J-W., 1996, Tumor angiogenesis. an independent prognostic parameter in cervical cancer, Am. J. Obstet. Gynecol. 174(1 Pt 1): 126–31.PubMedCrossRefGoogle Scholar
  15. Brooks, P. C., Montgomery, A. M. P., Rosenfeld, M., Reisfeld, R. A., Hu, T., Ilier, G., Cheresh, D. A., 1994,. Integrin αvβ3 antagonists promote tumor regression by inducing apoptosis of angiogenic blood vessels, Cell 79:1157–1164.PubMedCrossRefGoogle Scholar
  16. Carnochan, P., Briggs, J. C., Westbury, G., Davies, A. J., 1991, The vascularity of cutaneous melanoma: a quantitative histologic study of lesions 0.85–1.25 mm in thickness, Brit. J. Cancer 64:102–107.PubMedCrossRefGoogle Scholar
  17. Charpin, C., Devictor, B., Bergeret, D., Andrac, L., Boulat, J., Horschowski, N., Lavaut, M. N., Piana, L., 1995, CD31 quantitative immunocytochemical assays in breast carcinomas. Correlation with current prognostic factors, Am. J. Clin. Pathol. 103:443–448.PubMedGoogle Scholar
  18. Costello, P., McCann, A., Carney, D. N., Dervan, P. A., 1995, Prognostic significance of microvessel density in lymph node negative breast carcinoma, Hum. Pathol. 26:1181–1184.PubMedCrossRefGoogle Scholar
  19. DeYoung, B. R., Wick, M. R., Fitzgibbon, J. F., Sirgi, K. E., Swanson, P. E., 1993, CD31: An immunospecific marker for endothelial differentiation in human neoplasms, Appl. Immunohistochem. 1:97–100.Google Scholar
  20. Dickinson, A. J., Fox, S. B., Persad, R. A., Hollyer, J., Sibley, G. N., Harris, A. L., 1994, Quantification of angiogenesis as an independent predictor of prognosis in invasive bladder carcinomas, Brit. J. Urol. 74:762–766.PubMedCrossRefGoogle Scholar
  21. Dray, T. G., Hardin, N. J., Sofferman, R. A., 1995, Angiogenesis as a prognostic marker in early head and neck cancer, Ann. Otol Rhinol. Laryngol. 104:724–729.PubMedGoogle Scholar
  22. Egawa, S., Tsutsumi, M., Konishi, Y., Kobari, M., Matsuni, S., Nagasaki, K., Futami, H., Yamaguchi, K., 1995, The role of angiogenesis in the tumor growth of Syrian hamster pancreatic cancer cell line HPD-NR,Gastroenterology 108:1536–1533.CrossRefGoogle Scholar
  23. Esserman, L., Hylton, N., George, T., Yassa, L., Weidner, N., (submitted), Constrast-enhanced magnetic resonance imaging (cMRI) provides a window to visualize anatomic extent and tumor angiogenesis in breast carcinoma, Cancer Res. Google Scholar
  24. Fallowfield, M. E., Cook, M. G., 1991, The vascularity of primary cutaneous melanoma, J. Pathol. 164:241–244.PubMedCrossRefGoogle Scholar
  25. Folkman, J., Watson, K., Ingber, D., Hanahan, D., 1989, Induction of angiogenesis during the transition from hyperplasia to neoplasia, Nature 339:58–61.PubMedCrossRefGoogle Scholar
  26. Folkman, J., 1994, Angiogenesis and breast cancer, J. Clin. Oncol. 12:441–443.PubMedGoogle Scholar
  27. Fontanini, G., Bigini, D., Vignati, S., Basolo, F., Mussi, A., Lucchi, M., Chine, S., Angeletti, C. A., Bevilacqua, G., 1995, Recurrence and death in non small cell lung carcinomas: a prognostic model using pathological parameters, microvessel count, and gene protein products, J. Pathol. 177:57–63.PubMedCrossRefGoogle Scholar
  28. Fox, S. B., Leek R. D., Smith, K., Hollyer, J., Greenall, M., Harris, A. L., 1994, Tumor angiogenesis in node-negative breast carcinomas: relationship with epidermal growth factor receptor, estrogen receptor, and survival, Breast Cancer Res. Treat. 29:109–116.PubMedCrossRefGoogle Scholar
  29. Fox, S. B., Stuart, N., Smith, K., Brunner, N., Harris, A. L., 1993, High levels of uPA and PA-1 are associated with highly angiogenic breast carcinomas, J. Pathol. 170 (Suppl):388a.Google Scholar
  30. Fregene, T. A., Khanuja, P. S., Noto, A. C., Gehani, S. K., Van Egmont, E. M., Luz, D. A., Pienta, K. J., 1993, Tumor- associated angiogenesis in prostate cancer, Anticancer Res. 13:2377–2381.PubMedGoogle Scholar
  31. Gasparini, G., Weidner, N., Bevilacqua, P., Maluta, S., Boracchi, P., Testolin, A., Pozza, F., Folkman, J., 1993, Intratumoral microvessel density and p53 protein: correlation with metastasis in head-and-neck squamous-cell carcinoma, Int. J. Cancer 55:739–744.PubMedCrossRefGoogle Scholar
  32. Gasparini, G., Bevilacqua, P., Boracchi, P., Maluta, S., Pozza, F., Barbareschi, M., Dalla Palma, P., Mezzett, M., Harris, A. L., 1994a, Prognostic value of p53 expression in early-stage breast carcinoma compared with tumour angiogenesis, epidermal growth factor receptor, c-erbB2, cathepsin D, DNA ploidy, parameters of cell kinetics and conventional features, Int. J. Oncol. 4:155–162.PubMedGoogle Scholar
  33. Gasparini, G., Weidner, N., Bevilacqua, P., Maluta, S., Dalla Palma, P., Caffo, O., Barbareschi, M., Boracchi, P., Marubini, E., Pozza, F., 1994b, Tumor microvessel density, p53 expression, tumor size, and peritumoral lymphatic vessel invasion are relevant prognostic markers in node-negative breast carcinoma, J. Clin. Oncol. 12:454–466.PubMedGoogle Scholar
  34. Gasparini, G., Barbareschi, M., Boracchi, P., Bevilacqua, P., Verderio, P., Dalla Palma, P., Menard, S., 1995a, 67-kDa laminin-receptor expression adds prognostic information to intra-tumoral microvessel density in node-negative breast cancer, Int. J. Cancer 60:604–610.PubMedCrossRefGoogle Scholar
  35. Gasparini, G., Barbareschi, M., Boracchi, P., Verderio, P., Caffo, O., Meli, S., Palma, P. D., Marubini, E., Bevilacqua, P., 1995b, Tumor angiogenesis may predict clinical outcome of node-positive breast cancer patients treated either with adjuvant hormone therapy or chemotherapy, Cancer J. Sci. Am. 1:131–141.PubMedGoogle Scholar
  36. Goulding, H., Rashid, N. F. N. A., Robertson, J. F., Bell, J. A., Elston, C. W., Blarney, R. W., Ellis, I. O., 1995, Assessment of angiogenesis in breast carcinoma: An important factor in prognosis? Hum. Pathol 26:1196–1200.PubMedCrossRefGoogle Scholar
  37. Graham, C. H., Rivers, J., Kerbel, R. S., Stankiewicz, K. S., White, W. L., 1994, Extent of vascularization as a prognostic indicator in thin (<0.76 mm) malignant melanomas, Am. J. Pathol. 145:510–514PubMedGoogle Scholar
  38. Hall, N. R., Fish, D. E., Hunt, N., Goldin, R. D., Guillou, P. J., Monson, J. R. T., 1992, Is the relationship between angiogenesis and metastasis in breast cancer real? Surg Oncol 1:223–229.PubMedCrossRefGoogle Scholar
  39. Hall, M. C., Troncoso, P., Pollack, A., Zhau, H. Y., Zagars, G. K., Chung, L. W., von Eschenbach, A. C., 1994, Significance of tumor angiogenesis in clinically localized prostate carcinoma treated with external beam radiotherapy, Urology 44:869–875.PubMedCrossRefGoogle Scholar
  40. Hollingsworth, H. C., Kohn, E. C., Steinberg, S. M., Rothenberg, M. L., Merino, M. J., 1995, Tumor angiogenesis in advanced stage ovarian carcinoma, Am. J. Pathol. 147:33–41.PubMedGoogle Scholar
  41. Horak, E., Leek, R., Klenk, N., LeJeune, S., Smith, K., Stuart, N., Greenall, M., Stepniewska, K., Harris, A. L., 1992, Angiogenesis, assessed by platelet/endothelial cell adhesion molecule antibodies, as indicator of node metastases and survival in breast cancer, Lancet 340:1120–1124.PubMedCrossRefGoogle Scholar
  42. Inada, K., Toi, M., Hoshina, S., Hayashi, K., Tominaga, T., 1995, Significance of tumor angiogenesis as an independent prognostic factor in axillary node-negative breast cancer, Gan. To. Kagaku Jap. J. Cancer Chemo. 22 (suppl 1): 59–65.Google Scholar
  43. Jaeger, T. M., Weidner, N., Chew, K., Moore, D. H., Kerschmann, R. L., Waldman, F. M., Carroll, P. R., 1995, Tumor angiogenesis correlates with lymph node metastases in invasive bladder cancer. J. Urol. 154:59–71.CrossRefGoogle Scholar
  44. Kainz, C., Speiser, P., Wanner, C., Obermair, A., Tempfer, C., Sliutz, G., Reinthaller, A., Breitenecker, G., 1995, Prognostic value of tumor microvessel density in cancer of the uterine cervix stage IB to IIB, Anticancer Res. 15:1549–1551.PubMedGoogle Scholar
  45. Kandel, J., Bossy-Wetzel, E., Radvani, F., Klagsburn, M., Folkman, J., Hanahan, D., 1991, Neovascularization is associated with a switch to the export of bFGF in the multi-step development of fibrosarcoma, Cell 66:1095–1104.PubMedCrossRefGoogle Scholar
  46. Kohno, Y., Iwanari, O., Kitao, M., 1993, Prognostic importance of histologic vascular density in cervical cancer treated with hypertensive intraarterial chemotherapy, Cancer 72:2394–2400.PubMedCrossRefGoogle Scholar
  47. Konno, H., Tanaka, T., Matsuda, I., Kanai, T., Maruo, Y., Nishino, N., Nakamura, S., Baba, S., 1995, Comparison of the inhibitory effect of the angiogenesis inhibitor TNP-470 and mitomycin C on the growth and liver metastasis of human colon cancer, Int. J. Cancer 61:268–271,PubMedCrossRefGoogle Scholar
  48. Leedy, D. A., Trune, D. R., Kronz, J. D., Weidner, N., Cohen, J. I., 1994, Tumor angiogenesis, the p53 antigen, and cervical metastasis in squamous carcinoma, Otolaryngol. Head Neck Surg 111:417–422.PubMedGoogle Scholar
  49. Leon, S. P., Folkerth, R. D., Black, P. M., 1996, Microvessel density is a prognostic indicator for patients with astroglial brain tumors, Cancer 77(2):362–72.PubMedCrossRefGoogle Scholar
  50. Li, V. W., Folkerth, R. D., Watanabe, H., Yu, C., Rupnick, M., Barnes, P., Scott, R. M., Black, P. M., Sallan, S.E., Folkman, J., 1994, Microvessel count and cerebrospinal fluid basic fibroblast growth factor in children with brain tumors, Lancet 334:82–86.CrossRefGoogle Scholar
  51. Lipponen, P., Ji, H., Aaltomaa, S., Syrjanen, K., 1994, Tumor vascularity and basement membrane structure in breast cancer as related to tumor histology and prognosis, J. Cancer Res. Clin. Oncol. 120:645–650.PubMedCrossRefGoogle Scholar
  52. Longacre, T. A., Rouse, R. V., 1994, CD31: A new marker for vascular neoplasia, Adv. Anat. Pathol. 1:16–20.CrossRefGoogle Scholar
  53. Macchiarini, P., Fontanini, G., Hardin, M. J., Hardin, M. J., Squartini, F., Angeletti, C. A., 1992, Relation of neovascularure to metastasis of non-small-cell lung cancer, Lancet 340:145–146.PubMedCrossRefGoogle Scholar
  54. Macchiarini, P., Fontanini, G., Dulmet, E., de Montpreville, V., Chapelier, A.R., Cerrin, J., Le Roy Ladurie, F., Dartevelle, P.G., 1994, Angiogenesis: an indicator of metastasis in non-small-cell lung cancer invading the thoracic inlet. Ann Thorac Surg 57:1534–1539.PubMedCrossRefGoogle Scholar
  55. MacLennan, G. T., Bostwick, D. G.1995, Microvessel density in renal cell carcinoma: lack of prognostic significance, Urology 46:27–30.PubMedCrossRefGoogle Scholar
  56. Maeda, K., Chung, Y.-S., Takatsuka, S., Ogawa, Y., Onoda, N., Sawada, T., Kato, Y., Nitta, A., Arimoto, Y., Kondo, Y., Sowa, M., 1995a, Tumor angiogenesis and tumor cell proliferation as prognostic indicators in gastric carcinoma, Br. J. Cancer 72:319–323.PubMedCrossRefGoogle Scholar
  57. Maeda, K., Chung, Y-S., Takatsuka, S., Ogawa, Y., Sawada, T., Yamashito, Y., Onoda, N., Kato, Y., Nitta, A., Arimoto, Y., Kondo, Y., Sowa, M., 1995b, Tumor angiogenesis as a predictor of recurrence in gastric carcinoma, J. Clin. Oncol. 13:477–481.PubMedGoogle Scholar
  58. Maeda, K., Chung, Y.-S., Ogawa, Y., Takatsuka, S., Kang, S., Ogawa, M., Sawada, T., Sowa, M., 1996, Prognostic value of vascular endothelial growth factor expression in gastric carcinoma, Cancer 77:858–863.PubMedCrossRefGoogle Scholar
  59. Mikami, Y., Tsukuda, M., Mochimatsu, I., Kokatsu, T., Yago, T., Sawaki, S., 1991, Angiogenesis in head and neck tumors, Nip. Jib. Gak. Kai. 96:645–50.CrossRefGoogle Scholar
  60. Miliaras, D., Kamas, A., Kalekou, H., 1995, Angiogenesis in invasive breast carcinoma: is it associated with parameters of prognostic significance? Histopathology 26:165–169.PubMedCrossRefGoogle Scholar
  61. Nguyen, M., Watanabe, H., Budson, A. E., Richie, J. P., Folkman, J., 1993, Elevated levels of the angiogenic peptide basic fibroblast growth factor in urine of bladder cancer patients, J. Natl. Cancer Instil 85:241–242.CrossRefGoogle Scholar
  62. Obermair, A., Czerwenka, K., Kurz, C., Buxbaum, P., Schemper, M., Sevela, P., 1994a, Influence of tumoral microvessel density on the recurrence-free survival in human breast cancer: preliminary results, Onkologie 17:44–49.CrossRefGoogle Scholar
  63. Obermair, A., Czerwenka, K., Kurz, C., Kaider, A., Sevelda, P., 1994b, Tumor vascular density in breast tumors and their effect on recurrence free survival, Chirurg. 65:611–615.PubMedGoogle Scholar
  64. Obermair, A., Kurz, C., Czervenka, K., Thoma, M., Kaider, A., Wagner, T., Gitsch, G., Sevelda, P., 1996,. Microvessel density and vessel invasion in lymph node negative breast cancer: effect on recurrence-free survival, Int. J. Cancer 62:126–130.CrossRefGoogle Scholar
  65. Ogawa, Y., Chung, Y-S., Nakata, B., Takatsuka, S., Maeda, K., Sawada, T., Kato, Y., Yoshikawa, K., Sakurai, M., Sowa, M., 1995, Microvessel quantitation in invasive beast cancer by staining for factor VIII-related antigen, Brit. J. Cancer 71: 1297–1301.PubMedCrossRefGoogle Scholar
  66. Olivarez, D., Ulbright, T., DeRiese, W., Foster, R., Reister, T., Einhorn, L., Sledge, G., 1994, Neovascularization in clinical stage A testicular germ cell tumor: prediction of metastatic disease, Cancer Res 54:2800–2802.PubMedGoogle Scholar
  67. Rutger, J. L., Mattox, T. F., Vargas, M. P., 1995, Angiogenesis in uterine cervical squamous cell carcinoma, Int. J. Gynecol Pathol 14:114–118.CrossRefGoogle Scholar
  68. Saclarides, T. J., Speziale, N. J., Drab, E., Szeluga, D. J., Rubin, D. B., 1994, Tumor angiogenesis and rectal carcinoma, Dis. Colon Rectum 37:921–926.PubMedCrossRefGoogle Scholar
  69. Schlenger, K., Hockel, M., Mitze, M., Schaffer, U., Weikel, W., Knapstein, P. G., Lambert, A., 1995, Tumor vascularity — A novel prognostic factor in advanced cervical carcinoma, Gynecol. Oncol. 59:57–66.PubMedCrossRefGoogle Scholar
  70. Schlingemann, R. O., Rietveld, F. J. R., Kwaspen, F., van de Kerkhof, P. C. M., de Waal, R. M. W., Ruiter, D. J., 1991, Differential expression of markers for endothelial cells, pericytes, and basal lamina in the microvasculature of tumors and granulation tissue, Am. J. Pathol 138:1335–1347.PubMedGoogle Scholar
  71. Scopinaro, F., Schillaci, O., Scarpini, M., Mingazzini, P. L., diMacio, L., Banci, M., Danieli, R., Zerilli, M., Limiti, M. R., CentiColella, A., 1994, Technetium-99m sestamibi: an indicator of breast cancer invasiveness, Eur. J. Nucl. Med. 21:984–987.PubMedCrossRefGoogle Scholar
  72. Shimoyama, S., Gansauge, F., Gansauge, S., Negri, G., Oohara, T., Beger, H. G., 1996, Increased angiogenin expression in pancreatic cancer is related to cancer aggressiveness, Cancer Res. 56:2703–2706.PubMedGoogle Scholar
  73. Siitonen, S. M., Haapasalo, H. K., Rantala, I. S., Helin, H. J., Isola, J. J., 1995, Comparison of different immunohistochemical methods in the assessment of angiogenesis: lack of prognostic value in a group of 77 selected node-negative breast carcinomas, Mod. Pathol 8:745–752.PubMedGoogle Scholar
  74. Smolle, J., Soyer, H-P., Hofmann-Wellenhof, R., Smolle-Juettner, F. M., Kerl, H., 1989, Vascular architecture of melanocytc skin tumors. A quantitative immunohistochemical study using automated image analysis, Pathol. Res. Pract. 185:740–745.PubMedCrossRefGoogle Scholar
  75. Srivastava, A., Laidlef, P., Hughes, L. E., Woodcock, J., Shedden, E. J., 1986, Neovascularization in human cutaneous melanoma: a quantitative morphological and Doppler ultrasound study, Eur. J. Cancer Clin. Oncol 22:1205–1209.PubMedCrossRefGoogle Scholar
  76. Srivastava, A., Laidler, P., Davies, R., Horgan, K., Hughes, L. E., 1988, The prognostic significance of tumor vascularity in intermediate-thickness (0.76–4.0 mm thick) skin melanoma, Am. J. Pathol. 133:419–23.PubMedGoogle Scholar
  77. Tahan, S. R., Stein, A. L., 1995, Angiogenesis in invasive squamous cell carcinoma of the lip: tumor vascularity is not an indicator of metastatic risk, J. Cutan. Pathol. 22:236–240.PubMedCrossRefGoogle Scholar
  78. Takebayashi, Y., Akiyama, S.-L., Yamada, K., Akiba, S., Aikou, T., 1996, Angiogenesis as an unfavorable prognostic factor in human colorectal carcinoma, Cancer 78:226–31.PubMedCrossRefGoogle Scholar
  79. Toi, M., Kashitani, J., Tominaga, T., 1993, Tumor angiogenesis is an independent prognostic indicator of primary breast carcinoma, Int. J. Cancer 55:371–374.PubMedCrossRefGoogle Scholar
  80. Toi, M., Hoshina, S., Yamamoto, Y., Ishii, T., Hayashi, K., Tominaga, T., 1994, Tumor angiogenesis in breast carcinoma: significance of vessel density as a prognostic indicator, Gan. To. Kagaku Ryoho Japanese J. Cancer Chemo. 21 (Suppl 2): 178–182.Google Scholar
  81. Toi, M., Inada, K., Suzuki, H., Tominaga, T., 1995, Tumor angiogenesis in breast cancer: its importance as a prognostic indicator and the association with vascular endothelial growth factor expression, Breast Cancer Res. Treat. 36:193–204.PubMedCrossRefGoogle Scholar
  82. Tomisaki, S., Ohno, S., Ichiyoshi, Y., Kuwano, H., Maehara, Y., Sugimachi, K., 1996, Microvessel quantification and its possible relation with liver metastasis in colorectal cancer, Cancer(Suppl), 77:1722–1728.PubMedGoogle Scholar
  83. Traweek, S. T., Kandalaft, P. L., Mehta, P., Battifora, H., 1991, The human hematopoietic progenitor cell antigen (CD34) in vascular neoplasia, Am. J. Clin. Pathol. 96:25–31.PubMedGoogle Scholar
  84. Vacca, A., Ribatti, D., Roncali, L., Lospalluti, M., Serio, G., Carrel, S., Dammacco, F., 1993, Melanocyte tumor progression is associated with changes in angiogenesis and expression of the 67-kilodalton laminin receptor, Cancer 72:455–461.PubMedCrossRefGoogle Scholar
  85. Vacca, A., Ribatti, D., Roncali, L., Ranieri, G., Serio, G., Silvestris, F., Dammacco, F., 1994, Bone marrow angiogenesis and progression in multiple myeloma, Brit. J. Haematol. 87:503–508.CrossRefGoogle Scholar
  86. Van Hoef, M. E. H. M., Knox, W. F., Dhesi, S. S., Howell, A., Schor, A. M., 1993, Assessment of tumor vascularity as a prognostic factor in lymph node negative invasive breast cancer, Eur. J. Cancer 29A: 1141–1145.CrossRefGoogle Scholar
  87. van de Rijn, M., Rouse, R.V., 1994, CD34: A review. Appl. Immunohistochem. 2:71–80.Google Scholar
  88. van Diest, P. J., Zevering, J. P., Zevering, L. C., Baak, J. P. A., 1995, Prognostic value of microvessel quantitation in cisplatin treated Figo 3 and 4 ovarian cancer patients, Pathol. Res. Pract. 191:25–30.PubMedCrossRefGoogle Scholar
  89. Vesalainen, S., Lipponen, P., Talja, M., Alhava, E., Syrjanen, K., 1994, Tumor vascularity and basement membrane structure as prognostic factors in T1–2M0 prostatic adenocarcinoma, Anticancer Res. 14:709–714.PubMedGoogle Scholar
  90. Visscher, D. W., Smilanetz, S., Drozdowicz, S., Wykes, S. M., 1993, Prognostic significance of image morphometric microvessel enumeration in breast carcinoma, Anal. Quant. Cytol. Histol. 15:88–92.PubMedGoogle Scholar
  91. Volm, M., Koomagi, R., Kaufmann, M., Mattern, J., Stammler, G., 1996, Microvessel density, expression of proto- oncogenes, and resistance-related proteins and incidence of metastases in primary ovarian carcinomas, Clin. Exp. Met. 14:209–14.Google Scholar
  92. Wakui, S., Furusato, M., Itoh, T., Sasaki, H., Akiyama, A., Kinoshita, I., Asano, K., Tokuda, T., Aizawa S., Ushigome, S., 1992, Tumor angiogenesis in prostatic carcinoma with and without bone marrow metastasis: a morphometric study, J. Pathol. 168:257–262.PubMedCrossRefGoogle Scholar
  93. Wang, J. M., Kumar, S., Pye, D., Haboubi, N., Al-Nakib, L., 1994, Breast carcinoma: comparative study of tumor vasculature using two endothelial-cell markers, J. Natl. Cancer Inst. 86:386–388.PubMedCrossRefGoogle Scholar
  94. Wang, J. M., Kumar, S., Pye, D., van Agthoven, A. J., Krupinski, J., Hunter, R. D., 1993, A monoclonal antibody detects heterogeneity in vascular endothelium of tumors and normal tissues, Int. J. Cancer 54:363–370.PubMedCrossRefGoogle Scholar
  95. Watanabe, I. I., Nguyen, M., Schizer, M., 1992, Basic fibroblast growth factor in human serum — a prognostic test for breast cancer, Mol. Biol. Cell. 3:324a.Google Scholar
  96. Weidner, N., 1992, The relationship of tumor angiogenesis and metastasis with emphasis on invasive breast carcinoma, in: Advances in Pathology and Laboratory Medicine, Volume 5 (R.S. Weinstein RS, ed), pp. 101–121, Mosby Year Book, Chicago.Google Scholar
  97. Weidner, N., Semple, J. P., Welch, W. R., Folkman, J., 1991, Tumor angiogenesis and metastasis — correlation in invasive breast carcinoma, N. Engl. J. Med. 324:1–8.PubMedCrossRefGoogle Scholar
  98. Weidner, N., Folkman, J., Pozza, F., Bevilacqua, P., Allred, E. N., Moore, D. H., Meli S., Gasparini G., 1992, Tumor angiogenesis: a new significant and independent prognostic indicator in early-stage breast carcinoma, J. Natl.Cancer Inst. 84:1875–1887.PubMedCrossRefGoogle Scholar
  99. Weidner, N., Carroll, P. R., Flax, J., Blumenfeld, W., Folkman, J., 1993, Tumor angiogenesis correlates with metastasis in invasive prostate carcinoma, Am. J. Pathol 143:401–409.PubMedGoogle Scholar
  100. Wiggins, D. L., Granai, C.O., Steinhoff, M. M., Calabresi, P., 1995, Tumor angiogenesis as a prognostic factor in cervical carcinoma, Gynecol. Oncol. 56:353–356.PubMedCrossRefGoogle Scholar
  101. Williams, J. K., Carlson, G. W., Cohen, C., Derose, P. B., Hunter, S., Jurkiewicz, M. J., 1994, Tumor angiogenesis as a prognostic factor in oral cavity tumors, Am. J. Surg. 168:373–380.PubMedCrossRefGoogle Scholar
  102. Yamazaki, K., Abe, S., Takekawa, H., Sukoh, N., Watanabe, N., Ogura, S., Nakajima, I., Isobe, H., Inoue, K., Kawakami, Y., 1994, Tumor angiogenesis in human lung adenocarcinoma, Cancer 74:2245–2250.PubMedCrossRefGoogle Scholar
  103. Yuan, A., Yang, P-C., Yu, C-J., Yao, Y-T., Lee, Y-C., Kuo, S-H., Luh, K-T., 1995, Tumor angiogenesis correlates with histologic type and nodal metastasis in non-small cell lung carcinoma, Am. J. Resp. Critical Care Med. Dec. 152(6 Pt 1): 2157–62.CrossRefGoogle Scholar
  104. Zatterstrom, U. K., Brun, E., Willen, R., Kjellen, E., Wennerberg, J., 1995, Tumor angiogenesis and prognosis in squamous cell carcinoma of the head and neck, Head & Neck 17:312–318.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1998

Authors and Affiliations

  • Noel Weidner
    • 1
  1. 1.Department of PathologyUniversity of CaliforniaSan FranciscoUSA

Personalised recommendations