Projects

Mapping MRI/MRS parameters with genetic over-expression profiles in human prostate cancer

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. 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 micro-peel techniques to generate “whole mount” molecular maps of radical prostatectomy specimens that correspond to pre-surgical MRI/MRS studies. An example is shown below.

Figure 1. Spatial overlay maps showing results of RNA microarray and rt-PCR analysis for AMACR, Choline kinase, NPY and VEGF. The color-coded maps derived from the analysis of DCEMRI as well as the histopathology (H and E stain) are shown for spatial reference. Note the two solid circles indicated in the tissue print grid that show the regions used for microarray analysis. (Click on image to enlarge.)

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. 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 over-expression of neuropeptide Y (NPY), a newly identified angiogenic factor, in a subset of prostate cancers, visualized on DCEMRI.