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Supervised Learning Model of Aligned Collagen for Human Breast Carcinoma Prognosis

J Bredfeldt

J Bredfeldt*, Y Liu , M Conklin , P Keely , K Eliceiri , T Mackie , University of Wisconsin, Madison, WI


SU-E-J-107 Sunday 3:00PM - 6:00PM Room: Exhibit Hall

Purpose: Our goal is to develop and apply a set of optical and computational tools to enable large-scale investigations of the interaction between collagen and tumor cells.

Methods: We have built a novel imaging system for automating the capture of whole-slide second harmonic generation (SHG) images of collagen in registry with bright field (BF) images of hematoxylin and eosin stained tissue. To analyze our images, we have integrated a suite of supervised learning tools that semi-automatically model and score collagen interactions with tumor cells via a variety of metrics, a method we call Electronic Tumor Associated Collagen Signatures (eTACS). This group of tools first segments regions of epithelial cells and collagen fibers from BF and SHG images respectively. We then associate fibers with groups of epithelial cells and finally compute features based on the angle of interaction and density of the collagen surrounding the epithelial cell clusters. These features are then processed with a support vector machine to separate cancer patients into high and low risk groups.

Results: We validated our model by showing that eTACS produces classifications that have statistically significant correlation with manual classifications. In addition, our system generated classification scores that accurately predicted breast cancer patient survival in a cohort of 196 patients. Feature rank analysis revealed that TACS positive fibers are more well aligned with each other, generally lower density, and terminate within or near groups of epithelial cells.

Conclusion: We are working to apply our model to predict survival in larger cohorts of breast cancer patients with a diversity of breast cancer types, predict response to treatments such as COX2 inhibitors, and to study collagen architecture changes in other cancer types. In the future, our system may be used to provide metastatic potential information to cancer patients to augment existing clinical assays.

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