Noninvasive detection of microsatellite instability in patients with endometrial cancer

Int J Cancer. 2023 May 15;152(10):2206-2217. doi: 10.1002/ijc.34435. Epub 2023 Jan 24.

Abstract

The analysis of mismatch repair proteins in solid tissue is the standard of care (SoC) for the microsatellite instability (MSI) characterization in endometrial cancer (EC). Uterine aspirates (UAs) or circulating-DNA (cfDNA) samples capture the intratumor heterogeneity and provide a more comprehensive and dynamic molecular diagnosis. Thus, MSI analysis by droplet-digital PCR (ddPCR) in UAs and cfDNA can provide a reliable tool to characterize and follow-up the disease. The UAs, paraffin-embedded tumor tissue (FFPE) and longitudinal plasma samples from a cohort of 90 EC patients were analyzed using ddPCR panel and compared to the SoC. A high concordance (96.67%) was obtained between the analysis of MSI markers in UAs and the SoC. Three discordant cases were validated as unstable by ddPCR on FFPE samples. Besides, a good overall concordance (70.27%) was obtained when comparing the performance of the ddPCR assay on UAs and cfDNA in high-risk tumors. Importantly, our results also evidenced the value of MSI analysis to monitor the disease evolution. MSI evaluation in minimally invasive samples shows great accuracy and sensitivity and provides a valuable tool for the molecular characterization and follow-up of endometrial tumors, opening new opportunities for personalized management of EC.

Keywords: cfDNA; ctDNA; disease monitoring; endometrial cancer; liquid biopsy; microsatellite instability; uterine aspirate.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell-Free Nucleic Acids*
  • Endometrial Neoplasms* / genetics
  • Female
  • Humans
  • Microsatellite Instability
  • Microsatellite Repeats
  • Polymerase Chain Reaction / methods

Substances

  • Cell-Free Nucleic Acids