Date: 28 Aug 2008

An illustration of the potential for mapping MRI/MRS parameters with genetic over-expression profiles in human prostate cancer

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Abstract

Introduction

Magnetic resonance imaging (MRI) and MR spectroscopy can probe a variety of physiological (e.g. blood vessel permeability) and metabolic characteristics of prostate cancer. However, little is known about the changes in gene expression that underlie the spectral and imaging features observed in prostate cancer. Tumor induced changes in vascular permeability and angiogenesis are thought to contribute to patterns of dynamic contrast enhanced (DCE) MRI images of prostate cancer even though the genetic basis of tumor vasculogenesis is complex and the specific mechanisms underlying these DCEMRI features have not yet been determined.

Materials and Methods

In order to identify the changes in gene expression that correspond to MRS and DCEMRI patterns in human prostate cancers, we have utilized tissue print micropeel techniques to generate “whole mount” molecular maps of radical prostatectomy specimens that correspond to pre-surgical MRI/MRS studies. These molecular maps include RNA expression profiles from both Affymetrix GeneChip microarrays and quantitative reverse transcriptase PCR (qrt-PCR) analysis, as well as immunohistochemical studies.

Results

Using these methods on patients with prostate cancer, we found robust over-expression of choline kinase a in the majority of primary tumors. We also observed overexpression of neuropeptide Y (NPY), a newly identified angiogenic factor, in a subset of prostate cancers, visualized on DCEMRI.

Conclusion

These studies set the stage for establishing MRI/MRS parameters as validated biomarkers for human prostate cancer.

This work was supported, in part, by a grant from the Ellison Foundation and grants from the National Institutes of Health, CA116465-02 (NMR), CA112220 and CA116866 (SMG) and RO1-CA-115296(JVF). B.N.B. was supported, in part, by Bayer Healthcare Pharmaceuticals. The authors would like to thank Dr. Melissa Upton, Dr. Jihad Hayek (pathology), and Dr. Fabio Grizzi (microvessel image analysis) for their guidance and assistance.