Abstract
Background
Angiogenesis is a fundamental component of oncogenesis. In this study we provided morphologic evidence of vascularization by using power Doppler ultrasound to correlate the clinicopathologic features of tumorigenesis, ER/c-erbB-2 expression, and tumor grade in invasive breast carcinoma.
Methods
Three indices (VI, vascularization index; FI, flow index; VFI, vascularization flow index) were used to analyze 3D power Doppler ultrasound images from 168 patients with malignant breast carcinoma and to correlate their clinicopathologic features.
Results
VI (the mean tumor vascularity) was correlated with ER negativity (p < 0.0029) and VFI (the overall perfusion) was correlated with ER positivity (p < 0.0029). HER2 positivity was statistically significantly correlated with tumor vasculature (VI, VFI) and tumor size/volume. FI (the mean blood flow volume) was significantly correlated with tumor size/volume, but VI was not. The univariate or multivariate logistic regression analysis also showed the reverse correlations between ER expression and tumor vascularity, and positive correlations between HER2 expression and tumor vascularity as well as tumor volume.
Conclusions
This morphologic evidence of vascularization is correlated with tumor angiogenesis and ER/c-erbB-2 co-expression, which could clarify the biology of breast cancer.
Similar content being viewed by others
References
Hsiao YH, Huang YL, Liang WM, Lin C, Kuo SJ, Chen DR. Characterization of benign and malignant solid breast masses: harmonic versus nonharmonic 3D power Doppler imaging. Ultrasound Med Biol. 2009;35:353–9.
Kuo SJ, Hsiao YH, Huang YL, Chen DR. Classification of benign and malignant breast tumors using neural networks and three-dimensional power Doppler ultrasound. Ultrasound Obstet Gynecol. 2008;32:97–102.
Carson PL, Moskalik AP, Govil A, Roubidoux MA, Fowlkes JB, Normolle D, et al. The 3D and 2D color flow display of breast masses. Ultrasound Med Biol. 1997;23:837–49.
Petit AM, Rak J, Hung MC, Rockwell P, Goldstein N, Fendly B, et al. Neutralizing antibodies against epidermal growth factor and ErbB-2/neu receptor tyrosine kinases down-regulate vascular endothelial growth factor production by tumor cells in vitro and in vivo: angiogenic implications for signal transduction therapy of solid tumors. Am J Pathol. 1997;151:1523–30.
Yen L, You XL, Al Moustafa AE, Batist G, Hynes NE, Mader S, et al. Heregulin selectively upregulates vascular endothelial growth factor secretion in cancer cells and stimulates angiogenesis. Oncogene. 2000;19:3460–9.
Vamesu S. Angiogenesis and c-erbB-2 (HER2/neu) overexpression status in primary breast cancer patients: an analysis of 158 needle core biopsies. Rom J Morphol Embryol. 2007;48:121–9.
Lee JE, Chung KW, Han W, Kim SW, Shin HJ, Bae JY, et al. Effect of estrogen, tamoxifen and epidermal growth factor on the transcriptional regulation of vascular endothelial growth factor in breast cancer cells. Anticancer Res. 2004;24:3961–4.
Lee CN, Cheng WF, Chen CA, Chu JS, Hsieh CY, Hsieh FJ. Angiogenesis of endometrial carcinomas assessed by measurement of intratumoral blood flow, microvessel density, and vascular endothelial growth factor levels. Obstet Gynecol. 2000;96:615–21.
Yang WT, Tse GM, Lam PK, Metreweli C, Chang J. Correlation between color power Doppler sonographic measurement of breast tumor vasculature and immunohistochemical analysis of microvessel density for the quantitation of angiogenesis. J Ultrasound Med. 2002;21:1227–35.
Jarvela IY, Sladkevicius P, Kelly S, Ojha K, Nargund G, Campbell S. Three-dimensional sonographic and power Doppler characterization of ovaries in late follicular phase. Ultrasound Obstet Gynecol. 2002;20:281–5.
Chang WC, Chang DY, Huang SC, Shih JC, Hsu WC, Chen SY, et al. Use of three-dimensional ultrasonography in the evaluation of uterine perfusion and healing after laparoscopic myomectomy. Fertil Steril. 2009;92:1110–5.
Pairleitner H, Steiner H, Hasenoehrl G, Staudach A. Three-dimensional power Doppler sonography: imaging and quantifying blood flow and vascularization. Ultrasound Obstet Gynecol. 1999;14:139–43.
Poon RT, Fan ST, Wong J. Clinical implications of circulating angiogenic factors in cancer patients. J Clin Oncol. 2001;19:1207–25.
Elston CW, Ellis IO. Pathological prognostic factors in breast cancer. I. The value of histological grade in breast cancer: experience from a large study with long-term follow-up. Histopathology. 1991;19:403–10.
Bloom HJ, Richardson WW. Histological grading and prognosis in breast cancer; a study of 1409 cases of which 359 have been followed for 15 years. Br J Cancer. 1957;11:359–77.
Vogl G, Bartel H, Dietze O, Hauser-Kronberger C. HER2 is unlikely to be involved in directly regulating angiogenesis in human breast cancer. Appl Immunohistochem Mol Morphol. 2006;14:138–45.
Sullivan CA, Ghosh S, Ocal IT, Camp RL, Rimm DL, Chung GG. Microvessel area using automated image analysis is reproducible and is associated with prognosis in breast cancer. Hum Pathol. 2009;40:156–65.
Hanahan D, Folkman J. Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis. Cell. 1996;86:353–64.
Menard S, Balsari A, Casalini P, Tagliabue E, Campiglio M, Bufalino R, et al. HER-2-positive breast carcinomas as a particular subset with peculiar clinical behaviors. Clin Cancer Res. 2002;8:520–5.
Folkman J. Cancer: Principles and Practice of Oncology. 7th ed. Philadelphia: Lippincott Williams & Wilkins; 2005.
Author information
Authors and Affiliations
Corresponding author
Additional information
S.-T. Chen and S.-J. Kuo contributed equally to this work.
About this article
Cite this article
Chen, ST., Kuo, SJ., Wu, HK. et al. Power Doppler breast ultrasound: association of vascularization and ER/c-erbB-2 co-expression in invasive breast carcinoma. Breast Cancer 20, 152–158 (2013). https://doi.org/10.1007/s12282-011-0317-y
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12282-011-0317-y