Stromal tissue segmentation in Ki67 histology images based on cytokeratin-19 stain translation

Purpose: The diagnosis and prognosis of breast cancer relies on histopathology image analysis. In this context, proliferation markers, especially Ki67, are increasingly important. The diagnosis using these markers is based on the quantification of proliferation, which implies the counting of Ki67 positive and negative tumoral cells in epithelial regions, thus excluding stromal cells. However, stromal cells are often very difficult to distinguish from negative tumoral cells in Ki67 images and often lead to errors when automatic analysis is used. Approach: We study the use of automatic semantic segmentation based on convolutional neural networks (CNNs) to separate stromal and epithelial areas on Ki67 stained images. CNNs need to be accurately trained with extensive databases with associated ground truth. As such databases are not publicly available, we propose a method to produce them with minimal manual labelling effort. Inspired by the procedure used by pathologists, we have produced the database relying on knowledge transfer from cytokeratin-19 images to Ki67 using an image-to-image (I2I) translation network. Results: The automatically produced stroma masks are manually corrected and used to train a CNN that predicts very accurate stroma masks for unseen Ki67 images. An F-score value of 0.87 is achieved. Examples of effect on the KI67 score show the importance of the stroma segmentation. Conclusions: An I2I translation method has proved very useful for building ground-truth labeling in a task where manual labeling is unfeasible. With reduced correction effort, a dataset can be built to train neural networks for the difficult problem of separating epithelial regions from stroma in stained images where separation is very hard without additional information.
This work was supported by the Spanish Research Agency (AEI) (Project No. PID2020-116907RB-I00) of the call MCIN/AEI/10.13039/50110001103 and the European Regional Development Funds under program FEDER Catalunya 2014–2020 and SA18-014623 DIGIPATICS.
Peer Reviewed
Postprint (published version)