Learn to Estimate Genetic Mutation and Microsatellite Instability with Histopathology H&E Slides in Colon Carcinoma

SIMPLE SUMMARY: Colorectal cancer is one of the most common malignancies and the third leading cause of cancer-related mortality worldwide. Identifying KRAS, NRAS, and BRAF mutations and MSI status are closely related to the individualized therapeutic judgment and oncologic prognosis of CRC patients. In this study, we introduced a cascaded network framework with an average voting ensemble strategy to sequentially identify the tumor regions and predict gene mutations & MSI status from whole-slide H&E images. Experiments on a colorectal cancer dataset indicated that the proposed method can achieve high fidelity in both gene mutation prediction and MSI status estimation. In our testing set, the AUCs for KRAS, NRAS, BRAF, and MSI were ranged from 0.794 to 0.897. The results suggested that the deep convolutional networks have the potential to assist pathologists in prediction of gene mutation & MSI status in colorectal cancer. ABSTRACT: Colorectal cancer is one of the most common malignancies and the third leading cause of cancer-related mortality worldwide. Identifying KRAS, NRAS, and BRAF mutations and estimating MSI status is closely related to the individualized therapeutic judgment and oncologic prognosis of CRC patients. In this study, we introduce a cascaded network framework with an average voting ensemble strategy to sequentially identify the tumor regions and predict gene mutations & MSI status from whole-slide H&E images. Experiments on a colorectal cancer dataset indicate that the proposed method can achieve higher fidelity in both gene mutation prediction and MSI status estimation. In the testing set, our method achieves 0.792, 0.886, 0.897, and 0.764 AUCs for KRAS, NRAS, BRAF, and MSI, respectively. The results suggest that the deep convolutional networks have the potential to provide diagnostic insight and clinical guidance directly from pathological H&E slides.