A Glimpse into Tumor Metabolism by Magnetic Resonance Spectroscopy: Choline Compounds and Choline Kinase Gene Expression in Human Breast Cancer
SD Herberger, D Kaul, CB Adkins, BL Smith, LL Cheng, MR Lentz, EF Brachtel. Massachusetts General Hospital, Boston
Background: Magnetic resonance (MR) imaging of the breast is a highly sensitive technique with increasing importance in the diagnosis of breast cancer, especially when multifocality is suspected or the tumor is not visible on mammography. However, tissue biopsies to fully characterize the MR-detected abnormalities are often necessary. MR spectroscopy is a further development that allows functional in vivo analysis of the tissue by assessing tissue metabolism. Prior cell-line studies indicated that the metabolic pathway catalyzed by the enzyme choline kinase- (CHK) is increased in malignancies. By studying human breast cancer tissue, we wish to correlate MR spectroscopy of the metabolite choline with molecular analysis of CHK and histopathological features.
Design: Fresh tissue samples of 5 invasive ductal carcinomas (IDC) and 5 invasive lobular carcinomas (ILC) were examined by MR spectroscopy with measurements of choline compounds. Molecular analysis of CHK mRNA was performed by real time PCR (qPCR) after laser capture microdissection and RNA extraction of malignant epithelial cells. Adjacent normal tissue served as matched control. Correlations between cholines, the corresponding CHK mRNA levels and histopathological tumor types were evaluated with standard statistical software.
Results: Higher expressions of CHK mRNA are associated with lower values of choline compounds in both IDC and ILC tumor samples (IDC: r2=0.91, p<0.012; ILC r2=0.78, p<0.047). Increased CHK mRNA levels in ILC result in more than 2.6-time reductions in choline compounds when compared with IDC. Matched benign tissue did not show decreased choline or increased CHK mRNA levels.
Conclusions: We show that CHK levels are inversely correlated with choline intensity in representative human breast cancer samples. Our results indicate that MR spectroscopy may differentiate malignant from benign tissue. Based on metabolomic characteristics, it may even be possible to distinguish morphologic subtypes of breast cancer such as lobular or ductal types. Further studies of the complete choline pathways will advance the understanding of both metabolic characteristics in human breast cancer and their features in MR spectroscopy.
Monday, March 9, 2009 1:00 PM
Poster Session II # 41, Monday Afternoon