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SIMS21, Poland 2017 - John S Fletcher abstract

John S Fletcher oral presentation (OB3-Tue3-1-4)

Imaging the Breast Cancer Tumour Microenvironment using GCIB-ToF-SIMS

Tina B Angerer1,2, Marwa Munem2, Ylva Magnusson3, Goran Landberg3, John S Fletcher2

1 University of Washington, 220 Molecular Engineering & Science Bldg, WA 98195-1653 Seattle, United States
2 University of Gothenburg - Department of Chemistry and Molecular Biology, Kemivagen 10, 412 96 Gothenburg, Sweden
3 University of Gothenburg - Sahlgrenska Cancer Center, Kemivagen 10, 412 96 Gothenburg, Sweden

Breast cancer is an umbrella term for a range of diseases where disease progression, treatment efficacy and ultimately, patient outcome vary due to the heterogeneity between patients, disease types and within the tumour region itself. The interplay between the tumour and the surrounding biochemical environment is an area of great interest and ToF-SIMS offers unique capabilities for characterising this complex microenvironment.

With the J105- 3D Chemical Imager (Ionoptika Ltd), fitted with a 40 kV gas cluster ion gun [1, 2], it is now possible to overcome some previous limitations of ToF-SIMS analysis and image large intact molecular species. To capitalize on these improved capabilities imaging ToF-SIMS analysis was performed on ductal mammary breast cancer sections, followed by H&E staining of the analysed sections. The ToF-SIMS analysis enabled chemically different areas of the diseased tissue to be distinguished. Multivariate analysis facilitated the localising and grouping the up to 10,000 different signals generated from the tissue to produce comprehensive chemical profiles assigned to different areas in the tissue and revealed underlying structures. A number of molecules have been identified that can be clearly assigned to the cancerous regions, characterised by conventional histological staining, in different breast cancer sections. Additionally, studying the distribution of specific single ions reveals reoccurring patterns of changes and gradients within the cancerous areas which cannot be observed in the conventionally stained image. Therefore ToF-SIMS can provide deeper insights into tumor metabolism and progression.

[1] J.F. Fletcher, S. Rabbani, A. Henderson, P. Blenkinsopp, S.P. Thompson, N.P. Lockyer, J.C. Vickerman, Anal. Chem., 80, 2008, 9058–9064.

[2] T.B. Angerer, P. Blenkinsopp, J.S. Fletcher, Int. J. Mass Spectrom., 377, 2015, 591-598.

[3] T.B. Angerer, Y. Magnusson, G. Landberg, J.S. Fletcher, Anal Chem, 88(23), 2016, 11946-11954