Molecular Characterization of Prostate Cancer with Associated Gleason Score Using Mass Spectrometry Imaging

被引:55
作者
Randall, Elizabeth C. [1 ]
Zadra, Giorgia [2 ,3 ]
Chetta, Paolo [3 ,4 ]
Lopez, Begona G. C. [5 ]
Syamala, Sudeepa [3 ]
Basu, Sankha S. [2 ]
Agar, Jeffrey N. [6 ]
Loda, Massimo [2 ,3 ]
Tempany, Clare M. [1 ]
Fennessy, Fiona M. [1 ,3 ]
Agar, Nathalie Y. R. [1 ,3 ,5 ]
机构
[1] Harvard Med Sch, Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA
[2] Harvard Med Sch, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA
[3] Harvard Med Sch, Dana Farber Canc Inst, Boston, MA 02115 USA
[4] Univ Milan, Milan, Italy
[5] Harvard Med Sch, Brigham & Womens Hosp, Dept Neurosurg, Boston, MA 02115 USA
[6] Northeastern Univ, Chem & Chem Biol, Boston, MA 02115 USA
关键词
DESORPTION ELECTROSPRAY-IONIZATION; DIAGNOSIS; BIOPSY; ADENOCARCINOMA; PROGRESSION; RECURRENCE; PREDICTION; PROGNOSIS; CARCINOMA; MARKERS;
D O I
10.1158/1541-7786.MCR-18-1057
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Diagnosis of prostate cancer is based on histologic evaluation of tumor architecture using a system known as the "Gleason score." This diagnostic paradigm, while the standard of care, is time-consuming, shows intraobserver variability, and provides no information about the altered metabolic pathways, which result in altered tissue architecture. Characterization of the molecular composition of prostate cancer and how it changes with respect to the Gleason score (GS) could enable a more objective and faster diagnosis. It may also aid in our understanding of disease onset and progression. In this work, we present mass spectrometry imaging for identification and mapping of lipids and metabolites in prostate tissue from patients with known prostate cancer with GS from 6 to 9. A gradient of changes in the intensity of various lipids was observed, which correlated with increasing GS. Interestingly, these changes were identified in both regions of high tumor cell density, and in regions of tissue that appeared histologically benign, possibly suggestive of precancerous metabolomic changes. A total of 31 lipids, including several phosphatidylcholines, phosphatidic acids, phosphatidylserines, phosphatidylinositols, and cardiolipins were detected with higher intensity in GS (4+3) compared with GS (3+4), suggesting they may be markers of prostate cancer aggression. Results obtained through mass spectrometry imaging studies were subsequently correlated with a fast, ambient mass spectrometry method for potential use as a clinical tool to support imageguided prostate biopsy.
引用
收藏
页码:1155 / 1165
页数:11
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