Microsatellite instability (MSI) is a molecular marker of deficient DNA mismatch repair (dMMR) that is found in approximately 15% of colorectal cancer (CRC) patients. Testing all CRC patients for MSI/dMMR is recommended as screening for Lynch Syndrome and, more recently, to determine eligibility for immune checkpoint inhibitors in advanced disease. However, universal testing for MSI/dMMR has not been uniformly implemented because of cost and resource limitations. Artificial intelligence has been used to predict MSI/dMMR directly from hematoxylin and eosin (H&E) stained tissue slides. We review the emerging data regarding the utility of machine learning for MSI classification, focusing on CRC. We also provide the clinician with an introduction to image analysis with machine learning and convolutional neural networks. Machine learning can predict MSI/dMMR with high accuracy in high quality, curated datasets. Accuracy can be significantly decreased when applied to cohorts with different ethnic and/or clinical characteristics, or different tissue preparation protocols. Research is ongoing to determine the optimal machine learning methods for predicting MSI, which will need to be compared to current clinical practices, including next-generation sequencing. Predicting response to immunotherapy remains an unmet need.
Hildebrand Lindsey A, Pierce Colin J, Dennis Michael, Paracha Munizay, Maoz Asaf
DNA mismatch repair, artificial intelligence, colorectal cancer, convolutional neural network, deep learning, digital pathology, immunotherapy, machine learning, microsatellite instability, tumor immunology