Angiogenesis in breast cancer

  • Noel Weidner
Part of the Cancer Treatment and Research book series (CTAR, volume 83)

Abstract

This chapter reviews the basic concepts of tumor angiogenesis as well as the role of measuring intratumoral micro vessel density as an independent prognostic indicator for predicting tumor growth and metastasis, not only in breast carcinoma, but also in other solid tumors. For a tumor to growth, the tumor cells must proliferate and the benign host tissues must form around the tumor cells. Moreover, to metastasize a variety of critically important interactions must occur between tumor cells and the non-neoplastic vasculature, immune system, and connective tissues. Tumor angiogenesis refers to the growth of new vessels toward and within the tumor. This tumor neovascularization is caused by factors released by the tumor cells and/or associated inflammatory cells. Initially, many investigators thought that tumor hyperemia resulted from expansion of pre-existing vessels [1,2], but during the last two to three decades it has become clear that tumor growth is dependent upon the growth of new vessels [3].

Keywords

Lymphoma Rubber Heparin Adenosine Sarcoma 

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References

  1. 1.
    Coman DR, Sheldon WF (1946) The significance of hyperemia around tumor implants. Am J Pathol 22:821–826.Google Scholar
  2. 2.
    Day ED (1964) Vascular relationships of tumor and host. Prog Exp Tumor Res 4:57–97.PubMedGoogle Scholar
  3. 3.
    Folkman J (1990) What is the evidence that tumors are angiogenesis-dependent? J Natl Cancer Ins 82:4–6.CrossRefGoogle Scholar
  4. 4.
    Folkman J (1971) Tumor angiogenesis: Therapeutic implications. N Engl J Med 285:1182–1186.PubMedCrossRefGoogle Scholar
  5. 5.
    Folkman J, Hochberg M, Knighton D (1974) Self-regulation of growth in three dimensions: The role of surface area limitations. In Control of Animal Cell Proliferation. B Clarkson, R Baserga (eds). Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press, pp 833–842.Google Scholar
  6. 6.
    Sutherland RM (1988) Cell and environment interactions in tumor microregions: The multicell spheroid model. Science 240:177–184.PubMedCrossRefGoogle Scholar
  7. 7.
    Sutherland RM, McCredie JA, Inch WR (1971) Growth of multicell spheroids in tissue culture as a model of nodular carcinomas. J Natl Cancer Inst 46:113–120.PubMedGoogle Scholar
  8. 8.
    Blood CH, Zetter BR (1990) Tumor interactions with the vasculature: Angiogenesis and tumor metastasis. Biochim Biophysi Acta 1032:89–118.Google Scholar
  9. 9.
    Gimbrone MA, Leapman S, Cotran RS, Folkman J (1972) Tumor dormancy in vivo by prevention of neovascularization. J Exp Med 136:261–276.PubMedCrossRefGoogle Scholar
  10. 10.
    Gimbrone MA, Cotran Leapman Folkman J (1974) Tumor growth neovascularization: An experimental model using rabbit cornea. J Natl Cancer Inst 52:413–427.PubMedGoogle Scholar
  11. 11.
    Antonelli-Orlidge A, Saunders KB, Smith SR, D’Amore PA (1989) An activated form of transforming growth factor-beta is produced by co-cultures of endothelial cells and pericytes. Proc Natl Acad Sci USA 86:4544–4588.PubMedCrossRefGoogle Scholar
  12. 12.
    Ausprunk DH, Folkman J (1977) Migration and proliferation of endothelial cells in preformed and newly formed blood vessels during tumor angiogenesis. Microvasc Res 14:53–65.PubMedCrossRefGoogle Scholar
  13. 13.
    Adam JA, Maggelakis A A (1990) Diffusion regulated growth characteristics of a spherical prevascular carcinoma. Bull Math Biol 52:549–582.PubMedGoogle Scholar
  14. 14.
    Roberts AB, Sporn MB, Assoian RK, Smith JM, Roche NS, Wakefield LM, Heine UI, Liotta LA, Falanga V, Kehrl JH, Fauci AS (1986) Transforming growth factor type-beta: Rapid induction of fibrosis and angiogenesis in vivo and stimulation of collagen formation in vitro. Proc Natl Aca Sci USA 83:4167–4171.CrossRefGoogle Scholar
  15. 15.
    Knighton D, Ausprunk D, Tapper D, Folkman J (1977) Avascular and vascular phases of tumor growth in the chick embryo. Br J Cancer 35:347–356.PubMedCrossRefGoogle Scholar
  16. 16.
    Lien W, Ackerman N (1970) The blood supply of experimental liver metastases. II. A microcirculatory study of normal and tumor vessels of the liver with the use of perfused silicone rubber. Surgery 68:334–340.PubMedGoogle Scholar
  17. 17.
    Thompson WD, Shiach KJ, Fraser RA, Mcintosh LC, Simpson JG (1987) Tumors acquire their vasculature by vessel incorporation, not vessel ingrowth. J Pathol 151:323–332.PubMedCrossRefGoogle Scholar
  18. 18.
    Skinner SA, Tutton PJM, O’Brien PE (1990) Microvascular architecture of experimental colon tumors in the rat. Cancer Res 50:2411–2417.PubMedGoogle Scholar
  19. 19.
    Vartanian R, Weidner N (1994) Correlation of intratumoral endothelial-cell proliferation with microvessel density (tumor angiogenesis) and tumor-cell proliferation in breast carcinoma. Am J Pathol 144:1188–1194.PubMedGoogle Scholar
  20. 20.
    Weidner N, Semple JP, Welch WR, Folkman J (1991) Tumor angiogenesis and metastasis — correlation in invasive breast carcinoma. N Engl J Med 324:1–8.CrossRefGoogle Scholar
  21. 21.
    Weidner N, Folkman J, Pozza F, Bevilacqua P, Allred EN, Moore DH, 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
  22. 22.
    Folkman J (1985) Angiogenesis and its inhibitors. In Impartant Advances in Oncology. VT De Vita, S Hellman, SA Rosenberg (eds). Philadelphia: JB Lippincott, pp 42–62.Google Scholar
  23. 23.
    Folkman J (1995) Clinical applications of angiogenesis research. N Engl J Med, in press.Google Scholar
  24. 24.
    Harris AL, Fox S, Bicknell R, Leek R, Reif M, LeJeune S, Kaklamanis L (1994) Gene therapy through signal transduction pathways and angiogenic growth factors as therapeutic targets in breast cancer. Cancer 74(Suppl):1021–1025.PubMedCrossRefGoogle Scholar
  25. 25.
    Ingber D, Fujita T, Kishimoto S, Katsuichi S, Kanamaru T, Brem H, Folkman J (1990) Synthetic analogues of fumagillin that inhibit angiogenesis and suppress tumor growth. Nature 348:555–557.PubMedCrossRefGoogle Scholar
  26. 26.
    Gross JL, Herblin WF, Dusak BA, Czerniak P, Diamond M, Dexter DL (1990) Modulation of solid tumor growth in vivo by bFGF. Proc Am Assoc Cancer Res 31:79.Google Scholar
  27. 27.
    Kim KJ, Li B, Winer J, Armanini M, Gillett N, Phillips HS, Ferrara N (1993) Inhibition of vascular endothelial growth factor-induced angiogenesis suppresses tumor growth in vivo. Nature 362:841–844.PubMedCrossRefGoogle Scholar
  28. 28.
    Hori A, Sasada R, Matsutani E, et al. (1991) Suppression of solid tumor growth by immunoneutralizing monoclonal antibody against human basic fibroblast growth factor. Cancer Res 51:6180–6184.PubMedGoogle Scholar
  29. 29.
    Millauer B, Shawver LK, Plate KH, Risau W, Ullrich A (1994) Glioblastoma growth inhibited in vivo by a dominant-negative Flk-1 mutant. Nature 367:576–579.PubMedCrossRefGoogle Scholar
  30. 30.
    Brooks PC, Montgomery AMP, Rosenfeld M, Reisfeld RA, Hu T, liier G, Cheresh DA (1994) Integrin αvß3 antagonists promote tumor regression by inducing apoptosis of angiogenic blood vessels. Cell 79:1157–1164.PubMedCrossRefGoogle Scholar
  31. 31.
    Nicosia RF, Tchao R, Leighton J (1986) Interactions between newly formed endothelial channels and carcinoma cells in plasma clot culture. Clin Exp Metastasis 4:91–104.PubMedCrossRefGoogle Scholar
  32. 32.
    Rak JW, Hegmann EJ, Lu C, Kerbel RS (1994) Progressive loss of sensitivity to endothelium-derived growth inhibitors expressed by human melanoma cells during disease progression. J Cell Physiol 159:245–255.PubMedCrossRefGoogle Scholar
  33. 33.
    Hamada J, Cavanaugh PG, Lotan O (1992) Separable growth and migration factors for large-cell lymphoma cells secreted by microvascular endothelial cells derived from target organs for metastasis. Br J Cancer 66:349–354.PubMedCrossRefGoogle Scholar
  34. 34.
    Folkman J (1994) Angiogenesis and breast cancer. J Clin Oncol 12:441–443.PubMedGoogle Scholar
  35. 35.
    Fox SB, Stuart N, Smith K, Brunner N, Harris AL (1993) High levels of uPA and PA-1 are associated with highly angiogenic breast carcinomas. J Pathol 170(Suppl):388a.Google Scholar
  36. 36.
    Moscatelli D, Gross J, Rifkin D (1981) Angiogenic factors stimulate plasminogen activator and collagenase production by capillary endothelial cells. J Cell Biol 91:201a.CrossRefGoogle Scholar
  37. 37.
    Folkman J, Klagsbrun M (1987) Angiogenic factors. Science 235:442–447.PubMedCrossRefGoogle Scholar
  38. 38.
    Furcht LT (1986) Critical factors controlling angiogenesis: Cell products, cell matrix, and growth factors. Lab Invest 55:505–509.PubMedGoogle Scholar
  39. 39.
    Denekamp J (1993) Review article: Angiogenesis, neovascular proliferation and vascular pathophysiology as targets for cancer therapy. Br J Radiol 66:181–196.PubMedCrossRefGoogle Scholar
  40. 40.
    Mahadevan V, Hart IR (1990) Metastasis and angiogenesis. Rev Oncol 3:97–103.Google Scholar
  41. 41.
    Auerbach R, Arensman R, Kubai L, Folkman J (1975) Tumor-induced angiogenesis: Lack of inhibition by irradiation. Int J Cancer 15:241–245.PubMedCrossRefGoogle Scholar
  42. 42.
    Sholley MN, Ferguson GP, Seibel HR, Montour JL, Wilson JD (1984) Mechanisms of neovascularization. Vascular sprouting can occur without proliferation of endothelial cells. Lab Invest 51:624–634.PubMedGoogle Scholar
  43. 43.
    Dvorak HF (1986) Tumors: Wounds that do not heal. Similarities between tumor stroma generation and wound healing. N Engl J Med 315:1650–1659.CrossRefGoogle Scholar
  44. 44.
    Folkman J, Klagsbrun M (1987) Angiogenic factors. Science 235:442–447.PubMedCrossRefGoogle Scholar
  45. 45.
    Polverini PJ, Leibovich SJ (1984) Induction of neovascularization in vivo and endothelial proliferation in vitro by tumor associated macrophages. Lab Invest 51:635–642.PubMedGoogle Scholar
  46. 46.
    Weidner N, Semple JP, Welch WR, Folkman J (1991) Tumor angiogenesis and metastasis — correlation in invasive breast carcinoma. N Engl J Med 324:1–8.PubMedCrossRefGoogle Scholar
  47. 47.
    Guidi AJ, Fisher L, Harris JR, Schnitt SJ (1994) Microvessel density and distribution in ductal carcinoma in situ of the breast. J Natl Cancer Inst 86:614–619.PubMedCrossRefGoogle Scholar
  48. 48.
    Smith-McCune KK, Weidner N, Bishop JM (1993) Cervical intraepithelial neoplasia (CIN) is angiogenic. Proc Am Assoc Cancer Res 34:74.Google Scholar
  49. 49.
    Baird A, Mormede P, Bohlen P (1985) Immunoreactive fibroblast growth factor in cells of peritoneal exudate suggests its identity with macrophage-derived growth factor. Biochiem Biophys Res Commun 126:358–364.CrossRefGoogle Scholar
  50. 50.
    Frater-Schroder M, Risau W, Hallmann R, Gautschi P, Bohlen P (1987) Tumor necrosis factor type a, a potent inhibitor of endothelial cell growth in vitro, is angiogenic in vivo. Proc Natl Acad Sci USA 84:5277–5281.PubMedCrossRefGoogle Scholar
  51. 51.
    Liebovich SJ, Plverini PJ, Shepard HM, Wiseman DM, Nusseir SVN (1987) Macrophage-induced angiogenesis is mediated by tumor necrosis factor-a. Nature 329:630–632.CrossRefGoogle Scholar
  52. 52.
    Schreiber AB, Winkler ME, Derynck R (1986) Transforming growth factor-alpha: A more potent angiogenic mediator than epidermal growth factor. Science 232:1250–1253.PubMedCrossRefGoogle Scholar
  53. 53.
    Hockel M, Jung W, Vaupel P, Rabes H, Khaledpour C, Wissler JH (1988) Purified monocyte-derived angiogenic substance (angiotropin) induces controlled angiogenesis associated with regulated tissue proliferation in rabbit skin. J Clin Invest 82:1075–1090.PubMedCrossRefGoogle Scholar
  54. 54.
    Folkman J, Klagsbrun M, Sasse J, Wadzinski M, Ingber D, Vlodavsk I (1988) Heparin-binding angiogenic protein — basic fibroblast growth factor — is stored within basement membrane. Am J Pathol 130:393–400.PubMedGoogle Scholar
  55. 55.
    Knighton D, Hunt T, Scheuenstuhl H, Halliday BJ, Werb Z, Banda MJ (1983) Oxygen tension regulates the expression of angiogenesis factor by macrophages. Science 221:1283–1285.PubMedCrossRefGoogle Scholar
  56. 56.
    Smolin G, et al. (1971) Lymphatic drainage from vasculrized rabbit cornea. Am J Opthalmoi 72:147–151.Google Scholar
  57. 57.
    Kessler D, Langer R, Pless N, Folkman J (1976) Mast cells and tumor angiogenesis. Int J Can 18:703–709.CrossRefGoogle Scholar
  58. 58.
    Glowacki J, Mulliken J (1982) Mast cells in hemangiomas and vascular malformations. Pediatrics 70:48–51.PubMedGoogle Scholar
  59. 59.
    Thornton S, Mueller S, Levine E (1983) Human endothelial cells: Use of heparin in cloning and long-term serial cultivation. Science 222:623–625.PubMedCrossRefGoogle Scholar
  60. 60.
    Dethlefsen SM, Matsuura N, Zetter BR (1990) Tumor growth and angiogenesis in wild type mast cell deficient mice. FASEB 4:A623.Google Scholar
  61. 61.
    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
  62. 62.
    Nguyen M, Watanabe H, Budson AE, Richie JP, Folkman J (1993) Elevated levels of the angiogenic peptide basic fibroblast growth factor in urine of bladder cancer patients. J Natl Cancer Ins 85:241–242.CrossRefGoogle Scholar
  63. 63.
    Brown LF, Berse B, Jackman RW, Tognazzi K, Manseau EJ, Dvorak HF, Senger DR (1993) Increased expression of vascular permeability factor (vascular endothelial growth factor) and its receptors in kidney and bladder carcinomas. Am J Pathol 143:1255–1262.PubMedGoogle Scholar
  64. 64.
    Brown LF, Berse B, Jackman RW, Tognazzi K, Manseau EJ, Senger DR, Dvorak HF (1993) Expression of vascular permeability factor (vascular endothelial growth factor) and its receptors in adenocarcinomas of the gastrointestinal tract. Cancer Res 53:4727–4735.PubMedGoogle Scholar
  65. 65.
    Senger DR, Van De Water L, Brown LF, Nagy JA, Yeo K-T, Yeo T-K, Berse B, Jackman RW, Dvorak AM, Dvorak HF (1993) Vascular permeability factor (VPF, VEGF) in tumor biology. Cancer Metab Rev 12:303–324.CrossRefGoogle Scholar
  66. 66.
    Goto F, Goto K, Weindel K, Folkman J (1993) Synergistic effects of vascular endothelial growth factor and basic fibroblast growth factor on the proliferation and cord formation of bovine capillary endothelial cells within collagen gels. Lab Invest 69:508–517.PubMedGoogle Scholar
  67. 67.
    Leibovich SJ, Polverini PJ, Fong TW, Harlow LA, Koch AE (1994) Production of angiogenic acitivity by human monocytes requires an L-arginine/nitric oxide-synthase-dependent effector mechanism. Proc Natl Acad Sci USA 91:4190–4194.PubMedCrossRefGoogle Scholar
  68. 68.
    Laniado-Schwartzman M, Lavrovsky Y, Stotlz RA, Conners MS, Falck JR, Chauhan K, Abraham NG (1994) Activation of nuclear factor kappa B and oncogene expression by 12(R)-hydroxyeicosatrienoic acid, an angiogenic factor in microvessel endothelial cells. J Biol Chem 269:2432–2437.Google Scholar
  69. 69.
    Bond MD, Vallee BL (1990) Replacement of residues of 8–22 of angiogenin with 7–21 of RNASE-A selectively affects protein-synthesis inhibition and angiogenesis. Biochemistry 29:3341–3349.PubMedCrossRefGoogle Scholar
  70. 70.
    Bouck N, Stoler A, Polverini PJ (1986) Coordinate control of anchorage independence, actin cytoskeleton and angiogenesis by human chromosome 1 in hamster-human hybrids. Cancer Res 46:5101–5105.PubMedGoogle Scholar
  71. 71.
    Rastinegjad F, Polverini PF, Bouck NP (1989) Regulation of the activity of a new inhibitor of angiogenesis by a cancer suppressor gene. Cell 56:345–355.CrossRefGoogle Scholar
  72. 72.
    Zajchowski DA, Band V, Trask DK, Kling D, Connoly JL, Sager R (1990) Suppression of tumor-forming ability and related traits in MCF -7 human breast cancer cells by fusion with immortal mam-mary epithelial cells. Proc Natl Acad Sci USA 87:2314–2318.PubMedCrossRefGoogle Scholar
  73. 73.
    Dameron KM, Volpert OV, Tainsky MS, Bouck N (1994) Control of angiogenesis in fibroblasts by p53 regulation of thrombospondin-1. Science 265:1582–1584.PubMedCrossRefGoogle Scholar
  74. 74.
    O’Reilly MS, Holmgren L, Shing Y, Chen C, Rosenthal RA, Moses M, Lane WS, Cao Y, Sage EH, Folkman J (1994) Angiostatin: A novel angiogenesis inhibitor that mediates the suppression of metastases by a Lewis lung carcinoma. Cell 79:315–328.PubMedCrossRefGoogle Scholar
  75. 75.
    Folkman J (1995) Angiogenesis in cancer, vascular, rheumatoid, and other disease. Nature Med 1:27–31.PubMedCrossRefGoogle Scholar
  76. 76.
    Fidler IJ, Gersten DM, Hart IR (1978) The biology of cancer invasion and metastasis. Adv Cancer Res 28:149–250.PubMedCrossRefGoogle Scholar
  77. 77.
    Nicolson G (1979) Cancer metastasis. Sci Am 240:66–76.Google Scholar
  78. 78.
    Weiss L (1976) Biophysical aspects of the metastatic cascade. In Fundamental Aspects of Metastasis. L Weiss (ed). Amsterdam: North Holland, pp 51–70.Google Scholar
  79. 79.
    Bernstein LR, Liotta LA (1994) Molecular mediators of interactions with extracellular matrix components in metastasis and angiogenesis. Curr Opin Oncol 6:106–113.PubMedCrossRefGoogle Scholar
  80. 80.
    Nagy JA, Brown LF, Senger DR, Lanir N, Van de Water L, Dvorak AM, Dvorak HF (1989) Pathogenesis of tumor stroma generation: A critical role for leaky blood vessels and fibrin deposition. Biochim Biophys Acta 948:305–26.PubMedGoogle Scholar
  81. 81.
    Moscatelli D, Gross J, Rifkin D (1981) Angiogenic factors stimulate plasminogen activator and collagenase production by capillary endothelial cells. J Cell Biol 91:201a.Google Scholar
  82. 82.
    Folkman J (1987) Angiogenesis. In Thrombosis and Haemostasis. M Verstraete, J Vermylen, R Lijnan, J Arnout (eds). Leuven: Leuven University Press, 24:583–596.Google Scholar
  83. 83.
    Liotta LA, Stracke ML (1988) In Breast Cancer: Cellular and Molecular Biology. ME Lippman, RB Dickson (eds). Boston: Kluwer Academic Publishers, pp 223–238.Google Scholar
  84. 84.
    Liotta L, Kleinerman J, Saidel G (1974) Quantitative relationships of intravascular tumor cells, tumor vessels, and pulmonary metastases following tumor implantation. Cancer Res 34:997–1004.PubMedGoogle Scholar
  85. 85.
    Liotta L, Saidel G, Kleinerman J (1976) The significance of hematogenous tumor cell clumps in the metastatic process. Cancer Res 36:889–894.PubMedGoogle Scholar
  86. 86.
    Kerbel RS, Waghorne C, Korczak B, Lagarde A, Breitman ML (1988) Clonal dominance of primary tumours by metastatic cells: Genetic analysis and biological implications. Cancer Surv 7:597–629.PubMedGoogle Scholar
  87. 87.
    Folkman J (1992) Tumor angiogenesis. In Cancer Medicine, 3rd ed. JF Holland, E Frei, RC Bast, DW Kufe, DL Morton, RR Weichselbaum (eds). Melbourne, PA: Lea & Febiger, Chap. 11.Google Scholar
  88. 88.
    Sugino T, Kawaguchi T, Suzuki T (1995) Stromal invasion is not essential to blood-borne metastasis in mouse mammary carcinoma. Scientific Program Booklet of the Pathological Society of Great Britain and Ireland, 170th Meeting, January 1995, abstract #161.Google Scholar
  89. 89.
    Brem S, Cotran R, Folkman J (1972) Tumor angiogenesis: A quantitative method for histologic grading. J Natl Cancer Inst 48:347–356.PubMedGoogle Scholar
  90. 90.
    Srivastava A, Laidler P, Davies R, Horgan K, Hughes LE (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
  91. 91.
    Weidner N, Semple JP, Welch WR, Folkman J (1991) Tumor angiogenesis and metastasis — correlation in invasive breast carcinoma. N Engl J Med 324:1–8.PubMedCrossRefGoogle Scholar
  92. 92.
    McComb RD, Jones TR, Pizzo SV, Bigner D (1982) Specificity and sensitivity of immunohis-tochemical dectection of factor VIII/von Villebrand factor antigen in formalin-fixed paraffin-embedded tissue. J Histochem Cytochem 30:371–377.PubMedCrossRefGoogle Scholar
  93. 93.
    Gown AM, de Wever N, Battifora H (1993) Microwave-based antigenic unmasking. A revolutionary new technique for routine immunohistochemistry. Appl Immunohistochem 1:256–266.Google Scholar
  94. 94.
    Folkman J, Watson K, Ingber D, Hanahan D (1989) Induction of angiogenesis during the transition from hyperplasia to neoplasia. Nature 399:58–61.CrossRefGoogle Scholar
  95. 95.
    Weidner N, Folkman J, Pozza F, Bevilacqua P, Allred EN, Moore DH, 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
  96. 96.
    Bosari S, Lee AKC, DeLellis RA, et al. (1992) Microvessel quantitation and prognosis in invasive breast carcinoma. Hum Pathol 23:755–761.PubMedCrossRefGoogle Scholar
  97. 97.
    Longacre TA, Rouse RV (1994) CD31: A new marker for vascular neoplasia. Adv Anat Pathol 1:16–20.CrossRefGoogle Scholar
  98. 98.
    Horak E, Leek R, Klenk N, LeJeune S, Smith K, Stuart N, Greenall M, Stepniewska K, Harris AL (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
  99. 99.
    Gasparini G, Weidner N, Bevilacqua P, Maluta S, Dalla Palma P, Caffo O, Barbareschi M, Boracchi P, Marubini E, Pozza F (1994) 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
  100. 100.
    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
  101. 101.
    Visscher DW, Smilanetz S, Drozdowicz S, Wykes SM (1993) Prognostic significance of image morphometric microvessel enumeration in breast carcinoma. Anal Quant Cytolol Histol 15:88–92.Google Scholar
  102. 102.
    Arihiro K, Inai K, Kurihara K, Takeda S, Kanefao M (1993) Distribution of laminin, type IV collagen, and fibronectin in the invasive component of breast carcinoma. Acta Pathol Jpn 43:758–764.PubMedGoogle Scholar
  103. 103.
    Sneige N, Singletary E, Sahin A, et al. (1992) Multiparameter analysis of potential prognostic factors in node negative breast cancer patients. Mod Pathol 5:18a.Google Scholar
  104. 104.
    Sahin AA, Sneige N, Ordonez GN, et al. (1993) Tumor angiogenesis detected by Ulex europaeus agglutinin 1 lectin (UEA1) and factor VIII immunostaining in node-negative breast carcinoma (NNBC) treated by mastectomy: Prediction of tumor recurrence. Mod Pathol 6:19a.Google Scholar
  105. 105.
    Obermair A, Czerwenka K, Kurz C, Buxbaum P, Schemper M, Sevela P (1994) Influenceof tumoral microvessel density on the recurrence-free survival in human breast cancer; Preliminary results. Onkologie 17:44–49.CrossRefGoogle Scholar
  106. 106.
    Bundred NJ, Bowcott M, Walls J, Faragher DD, Knox F (1994) Angiogenesis in breast cancer predicts node metastases and survival. Br J Surg 81:768.CrossRefGoogle Scholar
  107. 107.
    Macchiarini P, Fontanini G, Hardin MJ, Hardin MJ, Squartini F, Angeletti CA (1992) Relation of neovasculature to metastasis of non-small-cell lung cancer. Lancet 340:145–146.PubMedCrossRefGoogle Scholar
  108. 108.
    Macchiarini P, Fontanini G, Dulmet E, de Montpreville V, Chapelier AR, Cerrin J, Le Roy Ladurie F, Dartevelle PG (1994) Angiogenesis: An indicator of metastasis in non-small-cell lung cancer invading the thoracic inlet. Ann Thorac Surg 57:1534–1539.PubMedCrossRefGoogle Scholar
  109. 109.
    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
  110. 110.
    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
  111. 111.
    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.PubMedGoogle Scholar
  112. 112.
    Fregene TA, Khanuja PS, Noto AC, Gehani SK, Van Egmont EM, Luz DA, Pienta KJ (1993) Tumor-associated angiogenesis in prostate cancer. Anticancer Res 13:2377–2381.PubMedGoogle Scholar
  113. 113.
    Brawer MK, Deering RE, Brown M, Preston SD, Bigler SA (1994) Predictors of pathologic stage in prostate carcinoma. Cancer 73:678–687.PubMedCrossRefGoogle Scholar
  114. 114.
    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
  115. 115.
    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
  116. 116.
    Albo D, Granick MS, Jhala N, Atkinson B, Solomon MP (1994) The relationship of angiogenesis to biological activity in human squamous cell carcinomas of the head and neck. Ann Plast Surg 32:588–594,1994.PubMedCrossRefGoogle Scholar
  117. 117.
    Williams JK, Carlson GW, Cohen C, Derose PB, Hunter S, Jurkiewicz MJ (1994) Tumor angiogenesis as a prognostic factor in oral cavity tumors. Am J Surg 168:373–380.PubMedCrossRefGoogle Scholar
  118. 118.
    Petruzzelli GJ, Snyderman CH, Johnson JT, Myers EN (1993) Angiogenesis induced by head and neck squamous cell carcinoma xenografts in the chick embryo chorioallantoic membrane model. Ann Otol Rhinol Laryngol 102:215–221.PubMedGoogle Scholar
  119. 119.
    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
  120. 120.
    Saclarides TJ, Speziale NJ, Drab E, Szeluga DJ, Rubin DB (1994) Tumor angiogenesis and rectal carcinoma. Dis Colon Rectum 37:921–926.PubMedCrossRefGoogle Scholar
  121. 121.
    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
  122. 122.
    Hollingworth HC, Steinberg SM, Kohn E, Bryant B, Merino MJ (1994) Tumor angiogenesis advanced stage ovarian cancer. Mod Pathol 7:89a.Google Scholar
  123. 123.
    Jaeger TM, Weidner N, Chew K, Moore DH, Kerschmann RL, Waldman FM, Carroll PR (1994) Tumor angiogenesis and lymph node metastases in invasive bladder carcinoma. J Urol 151.-348A.Google Scholar
  124. 124.
    Barnhill RL, Fandrey K, Levy MA, Mihm MC, Hyman B (1992) Angiogenesis and tumor progression of melanoma. Quantitation of vascularity in melanocytic nevi and cutaneous melanoma. Lab Invest 67:331–337.PubMedGoogle Scholar
  125. 125.
    Barnhill RL, Levy MA (1993) Regressing thin cutaneous malignant melanomas (≤1.0mm) are associated with angiogenesis. Am J Pathol 143:99–104.PubMedGoogle Scholar
  126. 126.
    Nasser I, Tahan S (1993) Angiogenesis in malanocytic lesions and its relationship to tumor progression. Mod Pathol 6:35A.Google Scholar
  127. 127.
    Fallowfield ME, Cook MG (1991) The vascularity of primary cutaneous melanoma. J Pathol 164:241–244.PubMedCrossRefGoogle Scholar
  128. 128.
    Cockerell CJ, Sonnier G, Kelly L, Patel S (1994) Comparative analysis of neovascularization in primary cutaneous melanoma and Spitz nevus. Am J Dermatopathol 16:9–13.PubMedCrossRefGoogle Scholar
  129. 129.
    Graham CH, Rivers J, Kerbel RS, Stankiewicz KS, White WL (1994) Extent of vascularization as a prgnostic indicator in thin (<0.76mm) malignant melanomas. Am J Pathol 145:510–514.PubMedGoogle Scholar
  130. 130.
    Ewaskow SP, Collins CA, Conrad EU, Gown AM, Schmidt RA (1993) Quantitative assessment of blood vessel density and size in soft-tissue tumors. Mod Pathol 6:6A.Google Scholar
  131. 131.
    Li VW, Folkerth RD, Watanabe H, Yu C, Rupnick M, Barnes P, Scott RM, Black PM, Sallan SE, Folkman J (1994) Microvessel count and cerebrospinal fluid basic fibroblast growth factor in children with brain tumors. Lancet 334:82–86.CrossRefGoogle Scholar
  132. 132.
    Vacca A, Ribatti D, Roncali L, Ranieri g, Serio G, Silvestris F, Dammacco F (1994) Bone marrow angiogenesis and progression in multiple myeloma. Br J Haematol 87:503–508.PubMedCrossRefGoogle Scholar
  133. 133.
    Van Hoef MEHM, Knox WF, Dhesi SS, Howell A, Schor AM (1993) Assessment of tumor vascularity as a prognostic factor in lymph node negative invasive breast cancer. Eur J Cancer 29A:1141–1145.PubMedGoogle Scholar
  134. 134.
    Hall NR, Fish DE, Hunt N, Goldin RD, Guillou PJ, Monson JRT (1992) Is the relationship between angiogenesis and metastasis in breast cancer real? Surg Oncol 1:223–229.PubMedCrossRefGoogle Scholar
  135. 135.
    Camochan P, Briggs JC, Westbury G, Davies AJ (1991) The vascularity of cutaneous melanoma: A quantitative histologic study of lesions 0.85–1.25 mm in thickness. Br J Cancer 64:102–107.CrossRefGoogle Scholar
  136. 136.
    Leedy DA, Trune DR, Kronz JD, Weidner N, Cohen JI (1994) Tumor angiogenesis, the p53 antigen, and cervical metastasis in squamous carcinoma. Otolaryngol Head Neck Surg 111:417–422.PubMedGoogle Scholar
  137. 137.
    Weidner N (1992) The relationship of tumor angiogenesis and metastasis with emphasis on invasive breast carcinoma. In Advances in Pathology and Laboratory Medicine, Vol 5. RS Weinstein (ed). Chicago: Mosby Year Book, pp 101–121.Google Scholar
  138. 138.
    Ordonez NG, Batsakis JG (1984) Comparison of Ulex europaeus I lectin and factor VIII-related antigen in vascular lesions. Arch Pathol Lab Med 108:129–132.PubMedGoogle Scholar
  139. 139.
    Lee AKC, DeLillis RA, Wolfe HJ (1986) Intramammary lymphatic invasion in breast carcinomas. Evaluation using ABH isoantigens as endothelial markers. Am J Surg Pathol 10:589–594.PubMedCrossRefGoogle Scholar
  140. 140.
    Bettelheim R, Michell D, Gusterson BA (1984) Immunocytochemistry in the identification of vascular invasion in breast cancer. J Clin Pathol 37:364–366.PubMedCrossRefGoogle Scholar
  141. 141.
    Kiyoshi M, Rosai J, Burgdorf WHC (1980) Localization of factor VIII-related antigens in vascular endothelial cells using an immunoperoxidase method. Am J Surg Pathol 4:273–276.CrossRefGoogle Scholar
  142. 142.
    Mukai K, Rosai J (1984) Factor VIII-related antigen: An endothelial marker. In Advances in Immunohistochemistry. RA DeLellis (ed). New York: Masson Publishing USA, pp 253–261.Google Scholar
  143. 143.
    Nagle RB, Witte MH, Martinez AP, Witte CL, Hendrix MJC, Way D, Reed K (1987) Factor VIII-associated antigen in human lymphatic endothelium. Lymphology 20:20–24.PubMedGoogle Scholar
  144. 144.
    Lee AKC, DeLellis RA, Silverman ML, Wolfe HJ (1986) Perspectives in pathology. Lymphatic and blood vessel invasion in breast carcinoma: A useful prognostic indicator. Hum Pathol 17:984–987.PubMedCrossRefGoogle Scholar
  145. 145.
    Svanholm H, Nielsen K, Hauge P (1984) Factor VIII-related antigen and lymphatic collecting vessels. Virchows Arch A Pathol Anat 404:223–228.CrossRefGoogle Scholar
  146. 146.
    Ordonez NG, Brooks T, Thompson S, Batsakis JG (1987) Use of Ulex europaeus agglutinin I in the identification of lymphatic and blood vessel invasion in previously stained microscopic slides. Am J Surg Pathol 11:543–550.PubMedCrossRefGoogle Scholar
  147. 147.
    Jain RK (1989) Delivery of novel therapeutic agents in tumors: Physiologic barriers and strategies. J Natl Cancer Inst 81:570–576.PubMedCrossRefGoogle Scholar
  148. 148.
    Tanigawa N, Kanazawa T, Satomura K, et al. (1981) Experimental study on lymphatic vascular changes in the development of cancer. Lymphology 14:149–154.PubMedGoogle Scholar
  149. 149.
    Zeidman I, Copeland B, Warren S (1955) Experimental studies on the spread of cancer in the lymphatic system. II. Absence of lymphatic supply in carcinoma. Cancer 8:123–127.PubMedCrossRefGoogle Scholar
  150. 150.
    Gilchrist RK (1950) Surgical management of advanced cancer of the breast. Arch Surg 61:913–929.Google Scholar
  151. 151.
    Papadimitriou JM, Woods AE (1975) Structural and functional characteristics of the microcirculation in neoplasms. J Pathol 116:65–72.CrossRefGoogle Scholar
  152. 152.
    Barsky SH, Baker A, Siegal GP, Togo S, Liotta LA (1983) Use of anti-basement membrane antibodies to distinguish blood vessel capillaries from lymphatic capillaries. Am J Surg Pathol 7:667–677.PubMedCrossRefGoogle Scholar
  153. 153.
    Schlingemann RO, Rietveld FJR, Kwaspen F, van de Kerkhof PCM, de Waal RMW, Ruiter DJ (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
  154. 154.
    Traweek ST, Kandalaft PL, Mehta P, Battifora H (1991) The human hematopoietic progenitor cell antigen (CD34) in vascular neoplasia. Am J Clin Pathol 96:25–31.PubMedGoogle Scholar
  155. 155.
    Herlyn M, Clark WH, Rodeck U, Mancianti ML, Jambrosic J, Koprowski H (1987) Biology of tumor progression in human melanocytes. Lab Invest 56:461–474.PubMedGoogle Scholar
  156. 156.
    DeYoung BR, Wick MR, Fitzgibbon JF, Sirgi KE, Swanson PE (1993) CD31: An immunospecific marker for endothelial differentiation in human neoplasms. Appl Immunohistochem 1:97–100.Google Scholar
  157. 157.
    van de Rijn M, Rouse RV (1994) CD34: A review. Appl Immunohistochem 2:71–80.Google Scholar
  158. 158.
    Wang JM, 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
  159. 159.
    Wang JM, Kumar S, Pye D, van Agthoven AJ, Krupinski J, Hunter RD (1993) A monoclonal antibody detects heterogeneity in vascular endothelium of tumors and normal tissues. Int J Cancer 54:363–370.CrossRefGoogle Scholar
  160. 160.
    Barbareschi M, Gasparini G, Weidner N, Morelli L, Farti S, Eccher C, Fina P, Leonardi E, Mauri F, Bevilacqua P, Dalla Palma P (199●●) Microvessel density quantification in breast carcinomas: Assessment by manual vs. a computer-assisted image analysis system. Appl Immunohistochem, in press.Google Scholar
  161. 161.
    Watanabe II, 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
  162. 162.
    Nguyen M, Watanabe II, Budson AE (1994) Elevated levels of an angiogenic peptide, basic fibroblast growth factor, in the urine of patients with a wide spectrum of cancers. J Natl Cancer Inst 86:356.PubMedCrossRefGoogle Scholar

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© Kluwer Academic Publishers 1996

Authors and Affiliations

  • Noel Weidner

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