The role of MSI in cancer: five key insights from the National inter-SiRIC Congress on Tumors with Microsatellite Instability

The National Congress on Tumors with MSI was a must-attend for anyone seeking to understand how Microsatellite Instability (MSI) impacts cancer. The event was organized by CURAMUS research lab based in AP-HP Sorbonne Université

The two-day multidisciplinary congress brings international experts from genetics, computer scientists, pathologists and clinical oncologists together to discuss the latest developments and research in the field. 

Here are the top five most important insights from the event.

1. Technological advancements for precision diagnosis

Conventional methods like Immunohistochemistry (IHC) and Polymerase Chain Reaction (PCR) came under a lot of scrutiny, highlighting their efficacy and limitations for detecting MSI across various cancers. Experts highlighted an urgent need for novel methodologies to enhance MSI detection in diverse cancer types. Next-Generation Sequencing (NGS) emerged as a promising approach, which offers extensive marker coverage and the potential to evaluate tumor mutational burden (TMB), but its accuracy in identifying MSI requires refinement and validation.

Certain cancer types exhibit an extremely low prevalence of MSI. A challenge where pre-screening tools are essential. (Figure 1)

Figure 1: Overall prevalence of MSI in adult solid tumours by cancer type¹

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2. AI seeking to overcome screening challenges

Progress within deep learning-based biomarkers’ research demonstrated their potential as pre-screening tools; MSIntuit® CRC was highlighted as a promising tool to predict MSI based on a digital histology slide. There was a significant amount of research about whether other modalities, such as cardiac magnetic resonance images or text from clinical reports, could help develop these tools further. 

Discussions also tackled the prognostic impact of Lynch-related MSI cancer pre-screening, highlighting its link to treatment responses across various cancers.

3. Genomics illuminates unique pathways

Insights into the genomic intricacies of Mismatch Repair Deficiency (MMRd) within gliomas were fascinating. The research outlined distinct pathways and their prognostic implications, offering a glimpse into the complex relationship between MMR defects, tumor characteristics, and treatment responses. These genetic variations may significantly influence treatment approaches for these types of cancers, signifying a potential shift in treatment strategies.

4. Understanding MSI status = understanding outcomes

The impact of MSI status on tumor response and survival, particularly in neoadjuvant chemotherapy and immunotherapy, garnered significant attention. Tumor regression grading (TRG) emerged as a potential tool for guiding therapeutic decisions. However, challenges persist in standardizing TRG and integrating it into existing staging systems, sparking further debate.‍

5. The complex landscape of immunotherapy

Immunotherapy has recently undergone a paradigm shift in localized MSI cancer. Debates highlighted the need for a cautious approach when considering surgical interventions, treatment combinations, and a patient’s long-term outcomes. Determining optimal treatment combinations, identifying complete responders, and minimizing toxicity emerged as key areas that warranted more research and international collaboration.

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Watch the explainer video on the validation of MSIntuit® CRC published in Nature Communications

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¹ Kang, YJ., O’Haire, S., Franchini, F. et al. A scoping review and meta-analysis on the prevalence of pan-tumour biomarkers (dMMR, MSI, high TMB) in different solid tumours. Sci Rep 12, 20495 (2022). https://doi.org/10.1038/s41598-022-23319-1