title: Molecular mapping of tumor heterogeneity on clinical tissue specimens with multiplexed quantum dots.
abstract: Tumor heterogeneity is one of the most important and challenging problems not only in studying the mechanisms of cancer development but also in developing therapeutics to eradicate cancer cells. Here we report the use of multiplexed quantum dots (QDs) and wavelength-resolved spectral imaging for molecular mapping of tumor heterogeneity on human prostate cancer tissue specimens. By using a panel of just four protein biomarkers (E-cadherin, high-molecular-weight cytokeratin, p63, and alpha-methylacyl CoA racemase), we show that structurally distinct prostate glands and single cancer cells can be detected and characterized within the complex microenvironments of radical prostatectomy and needle biopsy tissue specimens. The results reveal extensive tumor heterogeneity at the molecular, cellular, and architectural levels, allowing direct visualization of human prostate glands undergoing structural transitions from a double layer of basal and luminal cells to a single layer of malignant cells. For clinical diagnostic applications, multiplexed QD mapping provides correlated molecular and morphological information that is not available from traditional tissue staining and molecular profiling methods.
authors.affiliation: Department of Biomedical Engineering and Chemistry, Emory University and Georgia Institute of Technology, 101 Woodruff Circle Suite 2001, Atlanta, Georgia 30322, USA.
authors.forename: Jian
authors.initials: J
authors.lastname: Liu
authors.forename: Stephen K
authors.initials: SK
authors.lastname: Lau
authors.forename: Vijay A
authors.initials: VA
authors.lastname: Varma
authors.forename: Richard A
authors.initials: RA
authors.lastname: Moffitt
authors.forename: Matthew
authors.initials: M
authors.lastname: Caldwell
authors.forename: Tao
authors.initials: T
authors.lastname: Liu
authors.forename: Andrew N
authors.initials: AN
authors.lastname: Young
authors.forename: John A
authors.initials: JA
authors.lastname: Petros
authors.forename: Adeboye O
authors.initials: AO
authors.lastname: Osunkoya
authors.forename: Tracey
authors.initials: T
authors.lastname: Krogstad
authors.forename: Brian
authors.initials: B
authors.lastname: Leyland-Jones
authors.forename: May D
authors.initials: MD
authors.lastname: Wang
authors.forename: Shuming
authors.initials: S
authors.lastname: Nie
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism; D006801:Humans; D018796:Immunoconjugates / Q000737:chemistry / Q000276:immunology; D008297:Male; D051379:Mice; D057054:Molecular Imaging / Q000379:methods*; D036103:Nanotechnology; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D045663:Quantum Dots; D011817:Rabbits; D015203:Reproducibility of Results; D013050:Spectrometry, Fluorescence; D013194:Staining and Labeling
chemical_list: D014408:Biomarkers, Tumor; D018796:Immunoconjugates