Correlation of angiogenic factors in breast cancer as determined by MRI and immuno-histochemistry

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: We investigated the correlation among physiologic parameters such as vascular volume and permeability measured by MRI and angiogenic markers such as mp53, Thrombospondin-1 (TSP-1), CD31 and CD105 vessel density determined by immunohistochemistry (IHC) in breast cancer. METHODS: Seventy-one breast cancers from 68 patients were examined by dynamic contrast enhanced MRI before biopsy or surgery. The MRI signal enhancement time course was measured from each cancer, and analyzed with a pharmacokinetic model to obtain the vascular volume parameter Vb and the out-flux transport rate K2. The surgical specimens were analyzed by IHC to obtain the expression level of 4 angiogenic markers (mp53, TSP-1, CD31 and CD105 vessel density). The histoscores of p53, TSP-1, and CD31 vessel density were combined to give an Angiogenesis Index (AI) for each cancer. RESULTS: In the IHC study, the CD31(staining all vessels) was higher than CD105 (staining neovessels), and showed a significant correlation (p< 0.0001). The mp53 was inversely correlated with the angiogenesis inhibitor TSP-1 (p< 0.0001). The higher mp53 was modestly correlated with increased CD31 vessel density (p< 0.05). However, we did not observe any significant correlation between any pair of the MRI and IHC parameters. Nevertheless, when only concerning small cancers less than 2 cm (n=17), the vascular permeability parameter K2 was associated with the Angiogenesis Index (AI, p< 0.05). CONCLUSIONS: Our studies indicate that there is a strong correlation among the 4 molecular angiogenic markers. The fact that the significant correlation between IHC and MRI parameters only existed in small cancers suggests that the heterogeneity of breast cancer might be an important factor in the assessment of angiogenesis.

KEY WORDS: p53, vascular permeability, vascular density.

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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 Angiogenesis.