| AVS 63rd International Symposium & Exhibition | |
| Biomaterial Interfaces | Tuesday Sessions |
| Session BI+AS+SA-TuA |
| Session: | Biophysics and Characterization of Biological and Biomaterial Surfaces |
| Presenter: | Blake Bluestein, University of Washington |
| Authors: | B.M. Bluestein, University of Washington F. Morrish, Fred Hutchinson Cancer Research Center D. Hockenbery, Fred Hutchinson Cancer Research Center L.J. Gamble, University of Washington |
| Correspondent: | Click to Email |
Breast cancer, the most common cancer among women, is known to vary in responsiveness to chemotherapy. Therefore, the role of changes in tumor metabolism affecting the response to chemotherapy is under scrutiny. Time-of-flight secondary ion mass spectrometry (ToF-SIMS) provides a powerful approach to attain spatially-resolved molecular data from cancerous tissues. We use imaging ToF-SIMS and principal components analysis (PCA) to study human biopsy tissue samples to clarify links between fatty acid composition within and around tumors and the potential drug resistance of these tumors. An important component of this project is ToF-SIMS analysis of pre and post neoadjuvant frozen patient specimens. Since treatment occurs with the tumor in place, analysis of biopsies taken pre- and post-treatment allows characterization of molecular changes in tumors as a response to treatment. Two sets of pre and post chemotherapeutic treated tissue have been studied. Additionally, 11 triple negative (TN) pre-treatment tissues have been studied using PCA to determine if molecular differences within tumor tissues can be correlated with patient response to treatment.
Data were acquired with an IONTOF TOF.SIMS V using a Bi3+ analysis beam. Multiple 1mm2 areas per tissue section were analyzed by stitching together 25 200μm2 raster area scans. Data was acquired in both positive and negative polarities. Scores images generated by imaging PCA correlated with cellular and stromal areas were then used as masks to select regions of interest (ROI) that were reconstructed with ToF-SIMS software. Reconstructed spectral data of cellular and stromal areas was subsequently analyzed using PCA to ascertain molecular differences between tumor tissues.
Utilizing ROIs to select specific regions within analysis areas followed by spectral PCA for two different sets of pre and post treatment tumor biopsies showed a near distinctive chemical separation between pre and post. Chemical differences observed between the pre and post treatment tissue biopsies were related to changes in fatty acids, monoacylglycerols, diacylglycerols and cholesterol. Pretreatment samples showed higher loadings for vitamin E and C18:1 while post treatment samples had higher loadings for sphingomyelin and saturated fatty acids (stearic acid and palmitic acid). Spectral PCA of cellular and stromal region data from the 11 TN tissues separates patients that respond to chemotherapy and those that do not. Patients that respond to chemotherapy show higher loadings of sphingomyelin and saturated fatty acids, while nonresponding patients correlate with loadings of cholesterol, C18:1 and C18:2.