Skip to main content
SpringerLink
Log in

Color-coded and spectral Doppler flow in breast carcinomas – Relationship with the tumor microvasculature

  • Published:
Breast Cancer Research and Treatment Aims and scope Submit manuscript

Abstract

The phenomenon of tumor angiogenesis is an important aspect of understanding tumor biology. Studies in breast carcinoma have shown microvessel density (MVD) assessed by immunohistochemistry to be of prognostic importance in primary breast cancer. On the other hand, recently developed highly sensitive color-coded Doppler techniques offer a noninvasive method to examine neovascularisation in breast tumors. The purpose of this study was to determine the relationship between Doppler flow parameters and microvessel count assessed by immunohistochemistry. Fifty-three patients with primary breast cancer were examined preoperatively with color-coded Doppler ultrasound. The obtained Doppler frequency spectra were analyzed for peak systolic flow velocity (Vmax). Following surgery, paraffin-embedded microsections were immunohistochemically stained for factor VIII-related antigen. Tumor angiogenesis was assessed by microvessel count under light microscopy. Undifferentiated tumors correlated with high MVD (p=0.009) whereas other clinicopathological parameters were not associated with MVD. Color Doppler signals were detected in 50 out of 53 breast tumors. Evaluation of tumor flow velocity with various clinicopathological parameters showed a significant correlation with tumor size (p=0.0001) and lymph node metastasis (p=0.02). However, there was no significant correlation between MVD and intratumoral blood flow velocity assessed by color-coded Doppler. Our findings showed that Doppler flow measurement did not correlate with the extent of tumor angiogenesis of breast cancer. The present data give circumstantial evidence that microvessel count assessed by immunohistochemistry reflects the microvascular network, whereas tumor vasculature documented by Doppler ultrasound supplies information on the macrovasculature.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Burger MM, Folkman J: UICC study group on basic and clinical cancer research: tumor angiogenesis. Int J Cancer 56: 311–313, 1994

    Google Scholar 

  2. Folkman J: Tumor angiogenesis: therapeutic implications. N Engl J Med 285: 1182–1186, 1971

    Google Scholar 

  3. Folkman J: How is blood vessel growth regulated in normal and neoplastic tissue? -GHA Clower Memorial Award Lecture. Cancer Res 46: 467–473, 1986

    Google Scholar 

  4. Folkman J, Watson K, Ingber D: Induction of angiogenesis during the transition from hyperplasia to neoplasia. Nature 339: 58–62, 1989

    Google Scholar 

  5. Liotta L, Kleinerman J, Saldel G: Quantitative relationships of intravascular tumour cells, tumour vessels, and pulmonary metastasis following tumour implantation. Cancer Res 34: 997–1004, 1974

    Google Scholar 

  6. Starkey JR, Crowle PK, Taubenberger S: Mast-cell-deficient W/W mice exhibit a decreased rate of tumour angiogenesis. Int J Cancer 42: 48–52, 1988

    Google Scholar 

  7. Weidner N, Semple SP, Welch WR, Folkman J: Tumor angiogenesis and metastasis - correlation in invasive breast carcinoma. N Engl J Med 324: 1–8, 1991

    Google Scholar 

  8. Weidner N, Folkman J, Pozza F, Brevilaqua P, Allred EN, Moore DH, Meli S, Gasparini G: Tumor angiogenesis: a new significant and independent prognostic indicator in early-stage breast carcinoma. J Natl Cancer Inst 84: 1875–1887, 1992

    Google Scholar 

  9. Bosari S, Lee AK, Delellis RA, Wiley BD, Heatley GJ, Silverman MI: Microvessel quantitation and prognosis in invasive breast carcinoma. Hum Pathol 23: 755–761, 1992

    Google Scholar 

  10. Gasparini G, Weidner N, Bevilaqua P, Maluta S, Palma PD, Caffo O, Barbareschi M, Marubini E, Pozza F: 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, 1994

    Google Scholar 

  11. Fox SB, Leek RD, Smith K, Hollyer J, Greenall M, Harris A: Tumor angiogenesis in node-negative breast carcinomas - relationship with epidermal growth factor, estrogen receptor and survival. Breast Cancer Res Treat 29: 109–116, 1994

    Google Scholar 

  12. Bevilacqua P, Barbareschi M, Verderio P, Boracchi P, Caffo O, Palma PD, Meli S, Weidner N, Gasparini G: 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, 1995

    Google Scholar 

  13. Toi M, Inada K, Suzuki H, Tominaga T: 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, 1995

    Google Scholar 

  14. Obermair A, Kurz C, Czerwenka K, Thoma M, Kaider A, Wagner T, Gitsch G, Sevelda P: Microvessel density and vessel invasion in lymph-node negative breast cancer: Effect on recurrence-free survival. Int J Cancer 62: 126–131, 1995

    Google Scholar 

  15. Kuwatsuru R, Shames D, Mühler A et al.: Quantification of tissue plasma volume in the rat by contrast-enhanced magnetic resonance imaging. Magn Reson Med 30: 76–80, 1993

    Google Scholar 

  16. Shames D, Kuwatsuru R, Vexler V, Mühler A, Brasch R: Measurement of capillary permeability to macromolecules by dynamic magnetic resonance imaging: a quantitative non-invasive technique. Magn Reson Med 29: 616–622, 1993

    Google Scholar 

  17. Van Dijke CF, Brasch RC, Roberts TPL, Weidner N, Mathur A, Shames DM, Mann JS, Demsar F, Lang P, Schwickert HC: Mammary carcinoma model: Correlation of macromolecular contrast-enhanced MR imaging characterizations of tumor microvasculature and histologic capillary density. Radiology 198: 813–818, 1996

    Google Scholar 

  18. Buadu LD, Murakami J, Murayama S, Hashiguchi N, Sakai S, Masuda K, Toyoshima S, Kuroki S, Ohno S: Breast lesions: correlation of contrast medium enhanced patterns on MR images with histopathologic findings and tumor angiogenesis. Radiology 200(3): 639–649, 1996

    Google Scholar 

  19. Cosgrove DO, Bamber JC, Davey JB: Color Doppler signals from breast tumours. Radiology 176: 175–180, 1990

    Google Scholar 

  20. Burns PN, Halliwell M, Wells PNT: Ultrasonic Doppler studies of the breast. Ultrasound Med Biol 8: 127, 1982

    Google Scholar 

  21. Srivastava A, Webster DJT, Woodcock JP: Role of Doppler ultrasound flowmetry in the diagnosis of breast lumps. Br J Surg 75: 851–853, 1988

    Google Scholar 

  22. Dock W, Grabenwöger F, Metz V: Tumor vascularisation: assessment with Duplex sonography. Radiology 181: 241–244, 1991

    Google Scholar 

  23. Sohn C, Grischke EM, Wallwiener D: Ultrasound diagnosis of blood flow in benign and malignant breast tumors. Geburtsh u Frauenheilk 52: 397–403, 1992

    Google Scholar 

  24. Dixon JM, Walsh J, Paterson D: Colour Doppler ultrasonography studies of benign and malignant breast lesions. Br J Surg 79: 259–260, 1992

    Google Scholar 

  25. Peters-Engl C, Medl M, Leodolter S: The use of colour-coded and spectral Doppler ultrasound in the differentiation of benign and malignant breast lesions. Br J Cancer 71: 137–139, 1995

    Google Scholar 

  26. Bloom HJ, Richardson WW: Histological grading and prognosis in breast cancer: a study of 1409 cases of which 359 have been followed up for 15 years. Br J Cancer 11: 359–377, 1957

    Google Scholar 

  27. Spona J, Bieglmayer C, Husslein P: Hormone serum levels and hormone contents of endometria in women with normal menstrual cycles. Gynecol Obst Invest 10: 71, 1979

    Google Scholar 

  28. McComb RD, Jones TR, Pizzo SV, Bigner D: Specificity and sensitivity of immunohistochemical detection of factor VIII/von Willebrand factor antigen in formalin-fixed paraffin-embedded tissue. J Histochem Cytochem 30: 371–377, 1982

    Google Scholar 

  29. Weidner N: Current pathologic methods for measuring intratumoral microvessel density within breast carcinoma and other solid tumors. Breast Cancer Res Treat 36: 169–180, 1995

    Google Scholar 

  30. Lee AK: Basement membrane and endothelial agents: their role in evaluation of tumor invasion and metastasis. In: DeLellis RA (ed) Advances in Immunohistochemistry. Raven Press, New York, 1988, pp 363–393

    Google Scholar 

  31. Lee WJ, Chu JS, Houng SJ, Chung MF, Wang SM, Chen KM: Breast cancer angiogenesis: a quantitative morphologic and Doppler imaging study. Ann Surg Oncol 2: 246–251, 1995

    Google Scholar 

  32. Huang SC, Yu CH, Huang RT, Hsu KF, Tsai YC, Chou CY: Intratumoral blood flow in uterine myoma correlated with a lower tumor size and volume, but not correlated with cell proliferation or angiogenesis. Obstet Gynecol 87: 1019–102, 1996

    Google Scholar 

  33. Grischke EM, Kaufmann M, Eberlein-Gonska M, Mattfeldt T, Sohn CH, Bastert G: Angiogenesis as a diagnostic factor in primary breast cancer: Microvessel quantitation by stereological methods and correlation with color Doppler sonography. Onkologie 17: 35–42, 1994

    Google Scholar 

  34. Algire GH, Chalkley HW, Legallais FY, Park HD: Vascular reactions of normal and malignant tumors in vivo. 1. Vascular reactions of mice to wounds and to normal and neoplastic transplants. J Natl Cancer Inst 6: 73–85, 1945

    Google Scholar 

  35. Ausprunk DH, Folkman J: Migration and proliferation of endothelial cells in preformed and newly formed blood vessels during angiogenesis. Microvasc Res 14: 53–65, 1977

    Google Scholar 

  36. Jain RK: Determinants of tumor blood flow: A review. Cancer Res 48: 2641–2658, 1988

    Google Scholar 

  37. Baxter LT, Jain RK: Transport of fluid and macromolecules in tumors. IV. A microscopic model of the perivascular distribution. Microvasc Res 41: 252–272, 1991

    Google Scholar 

  38. Less JR, Skalak TC, Sevick EM, Jain RK: Microvascular architecture in a mammary carcinoma: Branching patterns and vessel dimensions. Cancer Res 51: 265–273, 1991

    Google Scholar 

  39. Eskey CJ, Wolmark N, McDowell CL, Domach MM, Jain RK: Residence time distributions of various tracers in tumors: implications for drug delivery and blood flow measurement. J Natl Cancer Inst 86: 293–299, 1994

    Google Scholar 

  40. Patan S, Munn LL, Jain RK: Intussusceptive microvascular growth in a human colon adenocarcinoma xenograft: A novel mechanism of tumor angiogenesis. Microvasc Res 51: 260–272, 1996

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Gynecology and Obstetrics, Lainz Medical Center, Vienna, AUSTRIA

    Christian Peters-Engl, Michael Medl, Michael Mirau & Paul Sevelda

  2. Department of Gynecology and Obstetrics, University Hospital of Vienna, Austria

    Christian Wanner & Andreas Obermair

  3. Department of Clinical Pathology, University Hospital of Vienna, Austria

    Selcuk Bilgi

Authors
  1. Christian Peters-Engl
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Michael Medl
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Michael Mirau
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Christian Wanner
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Selcuk Bilgi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Paul Sevelda
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Andreas Obermair
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Peters-Engl, C., Medl, M., Mirau, M. et al. Color-coded and spectral Doppler flow in breast carcinomas – Relationship with the tumor microvasculature. Breast Cancer Res Treat 47, 83–89 (1998). https://doi.org/10.1023/A:1005992916193

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1005992916193

Search

Navigation