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Issue 6, 2016
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An unsupervised MVA method to compare specific regions in human breast tumor tissue samples using ToF-SIMS

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Abstract

Imaging time-of-flight secondary ion mass spectrometry (ToF-SIMS) and principal component analysis (PCA) were used to investigate two sets of pre- and post-chemotherapy human breast tumor tissue sections to characterize lipids associated with tumor metabolic flexibility and response to treatment. The micron spatial resolution imaging capability of ToF-SIMS provides a powerful approach to attain spatially-resolved molecular and cellular data from cancerous tissues not available with conventional imaging techniques. Three ca. 1 mm2 areas per tissue section were analyzed by stitching together 200 μm × 200 μm raster area scans. A method to isolate and analyze specific tissue regions of interest by utilizing PCA of ToF-SIMS images is presented, which allowed separation of cellularized areas from stromal areas. These PCA-generated regions of interest were then used as masks to reconstruct representative spectra from specifically stromal or cellular regions. The advantage of this unsupervised selection method is a reduction in scatter in the spectral PCA results when compared to analyzing all tissue areas or analyzing areas highlighted by a pathologist. Utilizing this method, stromal and cellular regions of breast tissue biopsies taken pre- versus post-chemotherapy demonstrate chemical separation using negatively-charged ion species. In this sample set, the cellular regions were predominantly all cancer cells. Fatty acids (i.e. palmitic, oleic, and stearic), monoacylglycerols, diacylglycerols and vitamin E profiles were distinctively different between the pre- and post-therapy tissues. These results validate a new unsupervised method to isolate and interpret biochemically distinct regions in cancer tissues using imaging ToF-SIMS data. In addition, the method developed here can provide a framework to compare a variety of tissue samples using imaging ToF-SIMS, especially where there is section-to-section variability that makes it difficult to use a serial hematoxylin and eosin (H&E) stained section to direct the SIMS analysis.

Graphical abstract: An unsupervised MVA method to compare specific regions in human breast tumor tissue samples using ToF-SIMS

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Publication details

The article was received on 20 Nov 2015, accepted on 09 Feb 2016 and first published on 15 Feb 2016


Article type: Paper
DOI: 10.1039/C5AN02406D
Citation: Analyst, 2016,141, 1947-1957
  • Open access: Creative Commons BY-NC license
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    An unsupervised MVA method to compare specific regions in human breast tumor tissue samples using ToF-SIMS

    B. M. Bluestein, F. Morrish, D. J. Graham, J. Guenthoer, D. Hockenbery, P. L. Porter and L. J. Gamble, Analyst, 2016, 141, 1947
    DOI: 10.1039/C5AN02406D

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