Relationship of microvessel density and VEGF with dynamic MRI parameters in breast cancer

O. Nalcioglu, Ph.D. a, M-Y Su, Ph.D. a, J. Fruehauf, MD/Ph.D. b, Y-C. Cheung, MD c, E. Mechetner, Ph.D. b, A. Kyshtoobayeva, MD b, S-C. Chen, MD c, S. Hsueh, MD c, Y-L. Wan, MD c

a John Tu & Thomas Yuen Center for Functional Onco-Imaging, University of California, Irvine, CA, USA b Oncotech Inc. Irvine, CA, USA c Linko Chang Gung Memorial Hospital, Taiwan

AIM: Vascular parameters such as vessel density and permeability measured by MRI (in-vivo) and averaged over the entire tumor, the hot spot volume, and pixel-by-pixel were compared with the immunohistochemistry (IHC) measurements (ex-vivo) to determine the correlation of the two techniques. METHODS: MRI was performed to study 108 malignant cancers from 105 patients. Three analysis methods were applied to measure the characteristic parameters from the entire cancer, the hot spot of the cancer, and pixel-by-pixel within the cancer. The early enhancement intensity and the fitted pharmacokinetic parameters were obtained for correlation. The paraffin blocks containing the most aggressive cancer specimen was analyzed by IHC staining to measure the CD31 microvessel density and the expression level of VEGF for assessment of angiogenesis. RESULTS: The MRI parameters obtained from 3 analysis methods showed very strong correlation among each another (p< 0.0001 for all tests). The linear regression coefficients in the comparison of the enhancement magnitude measured using the entire cancer and hot spot analyses ranged from 0.86-0.89, and 0.78-0.88 in the comparison of pharmacokinetic parameters. The coefficients for comparing the pharmacokinetic parameters obtained using the entire cancer and pixel-by-pixel analyses were higher (0.91-0.96). The cancers with higher VEGF expression had an increased CD31 microvessel density (p < 0.005). Unfortunately no significant correlation was found among the IHC angiogenic markers with any of the MRI parameters obtained by three analysis methods. CONCLUSIONS: The study presented here shows that the analysis of MRI studies, as long as a consistent strategy is applied, the obtained parameters can be representative of the dynamic contrast enhanced MRI properties of a tumor. Furthermore, the different strategies in MRI analysis could not account for the lack of strong correlation between MRI parameters and molecular angiogenic factors.

KEY WORDS: vascular density, vascular permeability, breast cancer, .

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Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Paris, France; February 9 - 12, 2002; in the section on Predictive Markers.