Person:

Cheng, Leo

Accurate interpretation and correlation of tissue spectroscopy with pathological conditions requires disease-specific tissue metabolite databases; however, specimens for research are often kept in frozen storage for various lengths of time. Whether such frozen storage results in alterations to the measured metabolites is a critical but largely unknown issue. In this study, human prostate tissues from specimens that had been stored at −80 °C for 32 months were analyzed with high resolution magic angle spinning (HRMAS) magnetic resonance (MR) spectroscopy, and compared with the initial measurements of the adjacent specimens from the same cases when snap frozen in the operation room and kept frozen for less than 24 hours. Results of the current study indicate that that the storage-induced metabolite alterations are below the limits that tissue MR spectroscopy can discriminate. Furthermore, quantitative pathology evaluations suggest the observed alterations in metabolite profiles measured from the adjacent specimens of the same prostates may be accounted for by tissue pathological heterogeneities and are not a result of storage conditions. Hence, these results indicate that long-term frozen storage of prostate specimens can be quantitatively analyzed by HRMAS MR spectroscopy without concerns regarding significant metabolic degradation or alteration.

PURPOSE: This study was designed to test whether metabolic characterization of intact, unaltered human rectal adenocarcinoma specimens is possible using the high-resolution magic angle spinning proton (1H) magnetic resonance spectroscopy technique. METHODS: The study included 23 specimens from five patients referred for ultrasonographic staging of suspected rectal cancer. Multiple biopsies of macroscopically malignant rectal tumors and benign rectal mucosa were obtained from each patient for a total of 14 malignant and 9 benign samples. Unaltered tissue samples were spectroscopically analyzed. Metabolic profiles were established from the spectroscopy data and correlated with histopathologic findings. RESULTS: Metabolomic profiles represented by principle components of metabolites measured from spectra differentiated between malignant and benign samples and correlated with the volume percent of cancer (P = 0.0065 and P = 0.02, respectively) and benign epithelium (P = 0.0051 and P = 0.0255, respectively), and with volume percent of stroma, and inflammation. CONCLUSIONS: Magnetic resonance spectroscopy of rectal biopsies has the ability to metabolically characterize samples and differentiate between pathological features of interest. Future studies should determine its utility in in vivo applications for non-invasive pathologic evaluations of suspicious rectal lesions.

According to World Health Organization (WHO) estimates, cancer is responsible for more deaths than all coronary heart disease or stroke worldwide, serving as a major public health threat around the world. High resolution magic angle spinning (HRMAS) magnetic resonance spectroscopy (MRS) has demonstrated its usefulness in the identification of cancer metabolic markers with the potential to improve diagnosis and prognosis for the oncology clinic, due partially to its ability to preserve tissue architecture for subsequent histological and molecular pathology analysis. Capable of the quantification of individual metabolites, ratios of metabolites, and entire metabolomic profiles, HRMAS MRS is one of the major techniques now used in cancer metabolomic research. This article reviews and discusses literature reports of HRMAS MRS studies of cancer metabolomics published between 2010 and 2015 according to anatomical origins, including brain, breast, prostate, lung, gastrointestinal, and neuroendocrine cancers. These studies focused on improving diagnosis and understanding patient prognostication, monitoring treatment effects, as well as correlating with the use of in vivo MRS in cancer clinics.

Prostate cancer alters cellular metabolism through events potentially preceding cancer morphological formation. Magnetic resonance spectroscopy (MRS)-based metabolomics of histologically-benign tissues from cancerous prostates can predict disease aggressiveness, offering clinically-translatable prognostic information. This retrospective study of 185 patients (2002–2009) included prostate tissues from prostatectomies (n = 365), benign prostatic hyperplasia (BPH) (n = 15), and biopsy cores from cancer-negative patients (n = 14). Tissues were measured with high resolution magic angle spinning (HRMAS) MRS, followed by quantitative histology using the Prognostic Grade Group (PGG) system. Metabolic profiles, measured solely from 338 of 365 histologically-benign tissues from cancerous prostates and divided into training-testing cohorts, could identify tumor grade and stage, and predict recurrence. Specifically, metabolic profiles: (1) show elevated myo-inositol, an endogenous tumor suppressor and potential mechanistic therapy target, in patients with highly-aggressive cancer, (2) identify a patient sub-group with less aggressive prostate cancer to avoid overtreatment if analysed at biopsy; and (3) subdivide the clinicopathologically indivisible PGG2 group into two distinct Kaplan-Meier recurrence groups, thereby identifying patients more at-risk for recurrence. Such findings, achievable by biopsy or prostatectomy tissue measurement, could inform treatment strategies. Metabolomics information can help transform a morphology-based diagnostic system by invoking cancer biology to improve evaluation of histologically-benign tissues in cancer environments.

Background: Prostate cancer (PCa), the most common cancer and second leading cause of cancer death in American men, presents the clinical challenge of distinguishing between indolent and aggressive tumors for proper treatment. PCa presents significant alterations in metabolic pathways that can potentially be measured using techniques like mass spectrometry (MS) or mass spectrometry imaging (MSI) and used to characterize PCa aggressiveness. MS quantifies metabolomic, proteomic, and lipidomic profiles of biological systems that can be further visualized for their spatial distributions through MSI. Methods: PubMed was queried for all publications relating to MS and MSI in human prostate cancer from April 2007 to April 2017. With the goal of reviewing the utility of MSI in diagnosis and prognostication of human PCa, MSI articles that reported investigations of PCa-specific metabolites or metabolites indicating PCa aggressiveness were selected for inclusion. Articles were included that covered MS and MSI principles, limitations, and applications in PCa. Results: We identified nine key studies on MSI in intact human prostate tissue specimens that determined metabolites which could either differentiate between benign and malignant prostate tissue or indicate prostate cancer aggressiveness. These MSI-detected biomarkers show promise in reliably identifying PCa and determining disease aggressiveness. Conclusions: MSI represents an innovative technique with the ability to interrogate cancer biomarkers in relation to tissue pathologies and investigate tumor aggressiveness. We propose MSI as a powerful adjuvant histopathology imaging tool for prostate tissue evaluations, where clinical translation of this ex vivo technique could make possible the use of MSI for personalized medicine in diagnosis and prognosis of prostate cancer. Moreover, the knowledge provided from this technique can majorly contribute to the understanding of molecular pathogenesis of PCa and other malignant diseases.