Artificial Intelligence and Whole Slide Imaging, a new tool for the Microsatellite Instability prediction in Colorectal Cancer: friend or foe?

Colorectal cancer (CRC) is the third most common and second most deadly cancer worldwide. Despite advances in screening and treatment, CRC is heterogeneous and the response to therapy varies significantly, limiting personalized treatment options. Certain molecular biomarkers, including microsatellite instability (MSI), are critical in planning personalized treatment, although only a subset of patients may benefit. Currently, the primary methods for assessing MSI status include immunohistochemistry (IHC) for DNA mismatch repair proteins (MMRs), polymerase chain reaction (PCR)-based molecular testing, or next-generation sequencing (NGS). However, these techniques have limitations, are expensive and time-consuming, and often result in inter-method inconsistencies. Deficient mismatch repair (dMMR) or high microsatellite instability (MSI-H) are critical predictive biomarkers of response to immune checkpoint inhibitor (ICI) therapy and MSI testing is recommended to identify patients who may benefit. There is a pressing need for a more robust, reliable, and cost-effective approach that accurately assesses MSI status. Recent advances in computational pathology, in particular the development of technologies that digitally scan whole slide images (WSI) at high resolution, as well as new approaches to artificial intelligence (AI) in medicine, are increasingly gaining ground. This review aims to provide an overview of the latest findings on WSI and advances in AI methods for predicting MSI status, summarize their applications in CRC, and discuss their strengths and limitations in daily clinical practice.