Correlation of dynamic contrast enhancement MRI parameters with microvessel density and VEGF for assessment of angiogenesis in breast cancer
Corresponding Author
Min-Ying Su PhD
Center for Functional Onco-Imaging and Chao Family Comprehensive Cancer Center, University of California Irvine, Irvine, California
Min-Ying Su, Center for Functional Onco-Imaging, University of California, Irvine Hall 164, Irvine, CA 92697-5020
Yung-Liang Wan, First Department of Diagnostic Radiology, Change Gung Memorial Hospital at Linkou, College of Medicine and School of Medical Technology, Chang Gung University, 5 Fu-Hsing Road, Taoyuan, Taiwan 333
Search for more papers by this authorYun-Chung Cheung MD
Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan
Search for more papers by this authorHon Yu MS
Center for Functional Onco-Imaging and Chao Family Comprehensive Cancer Center, University of California Irvine, Irvine, California
Search for more papers by this authorOrhan Nalcioglu PhD
Center for Functional Onco-Imaging and Chao Family Comprehensive Cancer Center, University of California Irvine, Irvine, California
Search for more papers by this authorShin-Cheh Chen MD
Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan
Search for more papers by this authorSwei Hsueh MD
Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan
Search for more papers by this authorChristine E. McLaren PhD
Center for Functional Onco-Imaging and Chao Family Comprehensive Cancer Center, University of California Irvine, Irvine, California
Search for more papers by this authorCorresponding Author
Yung-Liang Wan MD
Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan
Min-Ying Su, Center for Functional Onco-Imaging, University of California, Irvine Hall 164, Irvine, CA 92697-5020
Yung-Liang Wan, First Department of Diagnostic Radiology, Change Gung Memorial Hospital at Linkou, College of Medicine and School of Medical Technology, Chang Gung University, 5 Fu-Hsing Road, Taoyuan, Taiwan 333
Search for more papers by this authorCorresponding Author
Min-Ying Su PhD
Center for Functional Onco-Imaging and Chao Family Comprehensive Cancer Center, University of California Irvine, Irvine, California
Min-Ying Su, Center for Functional Onco-Imaging, University of California, Irvine Hall 164, Irvine, CA 92697-5020
Yung-Liang Wan, First Department of Diagnostic Radiology, Change Gung Memorial Hospital at Linkou, College of Medicine and School of Medical Technology, Chang Gung University, 5 Fu-Hsing Road, Taoyuan, Taiwan 333
Search for more papers by this authorYun-Chung Cheung MD
Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan
Search for more papers by this authorHon Yu MS
Center for Functional Onco-Imaging and Chao Family Comprehensive Cancer Center, University of California Irvine, Irvine, California
Search for more papers by this authorOrhan Nalcioglu PhD
Center for Functional Onco-Imaging and Chao Family Comprehensive Cancer Center, University of California Irvine, Irvine, California
Search for more papers by this authorShin-Cheh Chen MD
Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan
Search for more papers by this authorSwei Hsueh MD
Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan
Search for more papers by this authorChristine E. McLaren PhD
Center for Functional Onco-Imaging and Chao Family Comprehensive Cancer Center, University of California Irvine, Irvine, California
Search for more papers by this authorCorresponding Author
Yung-Liang Wan MD
Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan
Min-Ying Su, Center for Functional Onco-Imaging, University of California, Irvine Hall 164, Irvine, CA 92697-5020
Yung-Liang Wan, First Department of Diagnostic Radiology, Change Gung Memorial Hospital at Linkou, College of Medicine and School of Medical Technology, Chang Gung University, 5 Fu-Hsing Road, Taoyuan, Taiwan 333
Search for more papers by this authorAbstract
Purpose
To investigate the association between parameters obtained from dynamic contrast enhanced MRI (DCE-MRI) of breast cancer using different analysis approaches, as well as their correlation with angiogenesis biomarkers (vascular endothelial growth factor and vessel density).
Materials and Methods
DCE-MRI results were obtained from 105 patients with breast cancer (108 lesions). Three analysis methods were applied: 1) whole tumor analysis, 2) regional hot-spot analysis, and 3) intratumor pixel-by-pixel analysis. Early enhancement intensities and fitted pharmacokinetic parameters were studied. Paraffin blocks of 71 surgically resected specimens were analyzed by immunohistochemical staining to measure microvessel counts (with CD31) and vascular endothelial growth factor (VEGF) expression levels.
Results
MRI parameters obtained from the three analysis methods showed significant correlations (P < 0.0001), but a substantial dispersion from the linear regression line was noted (r = 0.72–0.97). The entire region of interest (ROI) vs. pixel population analyses had a significantly higher association compared to the entire ROI vs. hot-spot analyses. Cancer specimens with high VEGF expression had significantly higher CD31 microvessel densities than did specimens with low VEGF levels (P < 0.005). No significant association was found between MRI parameters obtained from the three analysis strategies and IHC based measurements of angiogenesis.
Conclusion
A consistent analysis strategy was important in the DCE-MRI study. In this series, none of these strategies yielded results for MRI based quantitation of tumor vascularity that were associated with IHC based measurements. Therefore, different analyses could not account for the lack of association. J. Magn. Reson. Imaging 2003;18:467–477. © 2003 Wiley-Liss, Inc.
REFERENCES
- 1 Kuhl CK. MRI of breast tumors. Eur Radiol 2000; 10: 46–58.
- 2 Ercolani P, Valeri G, Amici F. Dynamic MRI of the breast. Eur J Radiol 1998; 27 Suppl 2: S265–S271.
- 3 Friedrich M. MRI of the breast: state of the art. Eur Radiol 1998; 8: 707–725.
- 4 Heywang-Köbrunner SH, Viehweg P, Heinig A, Küchler C. Contrast-enhanced MRI of the breast: accuracy, value, controversies, solutions. Eur J Radiol 1997; 24: 94–108.
- 5 Piccoli CW. Contrast-enhanced breast MRI: factors affecting sensitivity and specificity. Eur Radiol 1997; 7 Suppl 5: 281–288.
- 6 Kelcz F, Santyr G. Gadolinium-enhanced breast MRI. Crit Rev Diagn Imaging 1995; 36: 287–338.
- 7 Kuhl CK, Schild HH. Dynamic image interpretation of MRI of the breast. J Magn Reson Imaging 2000; 12: 965–974.
- 8 Mussurakis S, Buckley DL, Coady AM, Turnbull LW, Horsman A. Observer variability in the interpretation of contrast enhanced MRI of the breast. Br J Radiol 1996; 69: 1009–1016.
- 9 Mussurakis S, Buckley DL, Horsman A. Dynamic MR imaging of invasive breast cancer: correlation with tumour grade and other histological factors. Br J Radiol 1997; 70: 446–451.
- 10 Mussurakis S, Buckley DL, Horsman A. Dynamic MRI of invasive breast cancer: assessment of three region-of-interest analysis methods. J Comput Assist Tomogr 1997; 21: 431–438.
- 11
Liney GP,
Gibbs P,
Hayes C,
Leach MO,
Turnbull LW.
Dynamic contrast-enhanced MRI in the differentiation of breast tumors: user-defined versus semi-automated region-of-interest analysis.
J Magn Reson Imaging
1999;
10:
945–949.
10.1002/(SICI)1522-2586(199912)10:6<945::AID-JMRI6>3.0.CO;2-I CAS PubMed Web of Science® Google Scholar
- 12 Hulka CA, Smith BL, Sgroi DC, et al. Benign and malignant breast lesions: differentiation with echo-planar MR imaging. Radiology 1995; 197: 33–38.
- 13 Hulka CA, Edmister WB, Smith BL, et al. Dynamic echo-planar imaging of the breast: experience in diagnosing breast carcinoma and correlation with tumor angiogenesis. Radiology 1997; 205: 837–842.
- 14 Buckley DL, Drew PJ, Mussurakis S, Monson JR, Horsman A. Microvessel density of invasive breast cancer assessed by dynamic Gd-DTPA enhanced MRI. J Magn Reson Imaging 1997; 7: 461–464.
- 15 Stomper PC, Winston JS, Herman S, Klippenstein DL, Arredondo MA, Blumenson LE. Angiogenesis and dynamic MR imaging gadolinium enhancement of malignant and benign breast lesions. Breast Cancer Res Treat 1997; 45: 39–46.
- 16
Knopp MV,
Weiss E,
Sinn HP, et al.
Pathophysiologic basis of contrast enhancement in breast tumors.
J Magn Reson Imaging
1999;
10:
260–266.
10.1002/(SICI)1522-2586(199909)10:3<260::AID-JMRI6>3.0.CO;2-7 CAS PubMed Web of Science® Google Scholar
- 17 Weidner N. Current pathologic methods for measuring intratumoral microvessel density within breast carcinoma and other solid tumors. Breast Cancer Res Treat 1995; 36: 169–180.
- 18 Heimann R, Ferguson D, Gray S, Hellman S. Assessment of intratumoral vascularization (angiogenesis) in breast cancer prognosis. Breast Cancer Res Treat 1998; 52: 147–158.
- 19 Magennis DP. Angiogenesis: a new prognostic marker for breast cancer. Br J Biomed Sci 1998; 55: 214–220.
- 20 Gasparini G. Prognostic value of vascular endothelial growth factor in breast cancer. Oncologist 2000; 5 Suppl 1: 37–44.
- 21 Su MY, Jao JC, Nalcioglu O. Measurement of vascular volume fraction and blood-tissue permeability constants with a pharmacokinetic model: studies in rat muscle tumors with dynamic Gd-DTPA enhanced MRI. Magn Reson Med 1994; 32: 714–724.
- 22
Su MY,
Wang Z,
Carpenter PM,
Lao X,
Mühler A,
Nalcioglu O.
Characterization of N-ethyl-N-nitrosourea-induced malignant and benign breast tumors in rats by using three MR contrast agents.
J Magn Reson Imaging,
1999;
9:
177–186.
10.1002/(SICI)1522-2586(199902)9:2<177::AID-JMRI5>3.0.CO;2-8 CAS PubMed Web of Science® Google Scholar
- 23 Tofts PS. Modeling tracer kinetics in dynamic Gd-DTPA MR imaging. J Magn Reson Imaging 1997; 7: 91–101.
- 24
Su MY,
Wang Z,
Nalcioglu O.
Investigation of longitudinal vascular changes in control and chemotherapy-treated tumors to serve as therapeutic efficacy predictors.
J Magn Reson Imaging
1999;
9:
128–137.
10.1002/(SICI)1522-2586(199901)9:1<128::AID-JMRI17>3.0.CO;2-E CAS PubMed Web of Science® Google Scholar
- 25 Grant SW, Kyshtoobayeva AS, Kurosaki T, Jakowatz J, Fruehauf JP. Mutant p53 correlates with reduced expression of thrombospondin-1, increased angiogenesis, and metastatic progression in melanoma. Cancer Detect Prev 1998; 22: 185–194.
- 26 Mehta R, Kyshtoobayeva A, Kurosaki T, et al. Independent association of angiogenesis index with outcome in prostate cancer. Clin Cancer Res 2001; 7: 81–88.
- 27 Partridge SC, Gibbs JE, Lu Y, Esserman LJ, Sudilovsky D, Hylton NM. Accuracy of MR imaging for revealing residual breast cancer in patients who have undergone neoadjuvant chemotherapy. AJR Am J Roentgenol 2002; 179: 1193–1199.
- 28 Mussurakis S, Gibbs P, Horsman A. Peripheral enhancement and spatial contrast uptake heterogeneity of primary breast tumours: quantitative assessment with dynamic MRI. J Comput Assist Tomogr 1998; 22: 35–46.
- 29 Ikeda DM, Baker DR, Daniel BL. Magnetic resonance imaging of breast cancer: clinical indications and breast MRI reporting system. J Magn Reson Imaging 2000; 12: 975–983.
- 30 Degani H, Gusis V, Weinstein D, Fields S, Strano S. Mapping pathophysiological features of breast tumors by MRI at high spatial resolution. Nat Med 1997; 3: 780–782.
- 31 Kelcz F, Furman-Haran E, Grobgeld D, Degani H. Clinical testing of high-spatial-resolution parametric contrast-enhanced MR imaging of the breast. AJR Am J Roentgenol 2002; 179: 1485–1492.
- 32 Fitzgibbons PL, Page DL, Weaver D, et al. Prognostic factors in breast cancer. College of American Pathologists Consensus Statement 1999. Arch Pathol Lab Med 2000; 124: 966–978.
- 33 Senger DR, Van de Water L, Brown LF, et al. Vascular permeability factor (VPF, VEGF) in tumor biology. Cancer Metastasis Rev 1993; 12: 303–324.
- 34 Toi M, Inada K, Hoshina S, Suzuki H, Kondo S, Tominaga T. Vascular endothelial growth factor and platelet-derived endothelial cell growth factor are frequently coexpressed in highly vascularized human breast cancer. Clin Cancer Res 1995; 1: 961–964.
- 35
Toi M,
Kondo S,
Suzuki H, et al.
Quantitative analysis of vascular endothelial growth factor in primary breast cancer.
Cancer
1996;
77:
1101–1106.
10.1002/(SICI)1097-0142(19960315)77:6<1101::AID-CNCR15>3.0.CO;2-5 CAS PubMed Web of Science® Google Scholar
- 36
Obermair A,
Kucera E,
Mayerhofer K, et al.
Vascular endothelial growth factor (VEGF) in human breast cancer: correlation with disease-free survival.
Int J Cancer
1997;
74:
455–458.
10.1002/(SICI)1097-0215(19970822)74:4<455::AID-IJC17>3.0.CO;2-8 CAS PubMed Web of Science® Google Scholar
- 37 Buckley DL, Mussurakis S, Horsman A. Effect of temporal resolution on the diagnostic efficacy of contrast-enhanced MRI in the conservatively treated breast. J Comput Assist Tomogr 1998; 22: 47–51.
- 38 Schorn C, Fischer U, Luftner-Nagel S, Grabbe E. Diagnostic potential of ultrafast contrast-enhanced MRI of the breast in hypervascularized lesions: are there advantages in comparison with standard dynamic MRI? J Comput Assist Tomogr 1999; 23: 118–122.
- 39 Sardanelli F, Rescinito G, Giordano GD, Calabrese M, Parodi RC. MR dynamic enhancement of breast lesions: high temporal resolution during the first-minute versus eight-minute study. J Comput Assist Tomogr 2000; 24: 724–731.
- 40 Orel SG, Schnall MD. MR imaging of the breast for the detection, diagnosis, and staging of breast cancer. Radiology 2001; 220: 13–30.
- 41 Hawighorst H, Knapstein PG, Knopp MV, et al. Uterine cervical carcinoma: comparison of standard and pharmacokinetic analysis of time-intensity curves for assessment of tumor angiogenesis and patient survival. Cancer Res 1998; 58: 3598–3602.
- 42 Hawighorst H, Weikel W, Knapstein PG, et al. Angiogenic activity of cervical carcinoma: assessment by functional magnetic resonance imaging-based parameters and a histomorphological approach in correlation with disease outcome. Clin Cancer Res 1998; 4: 2305–2312.