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Address correspondence to snie@emory.edu

Reprinted (adapted) with permission from Liu, J., Lau, S. K., Varma, V. A., Moffitt, R. A., Caldwell, M., Liu, T., Young, A. N., et al. (2010). Molecular Mapping of Tumor Heterogeneity on Clinical Tissue Specimens with Multiplexed Quantum Dots. ACS Nano, 4(5), 2755–2765. doi:10.1021/nn100213v. Copyright 2010 American Chemical Society.

Subjects:

Research Funding:

National Cancer Institute : NCI

Keywords:

  • quantum dot
  • tumor heterogeneity
  • prostate cancer
  • multiplexing
  • spectral imaging
  • biomarker
  • immunohistochemistry

Molecular Mapping of Tumor Heterogeneity on Clinical Tissue Specimens with Multiplexed Quantum Dots

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Journal Title:

ACS Nano

Volume:

Volume 4, Number 5

Publisher:

, Pages 2755-2765

Type of Work:

Article | Post-print: After Peer Review

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 α-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.
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