Noninvasive detection of microsatellite instability in patients with endometrial cancer

• Published in: International journal of cancer Vol. 152; no. 10; pp. 2206 - 2217
• Main Authors: Casas‐Arozamena, Carlos, Moiola, Cristian Pablo, Vilar, Ana, Bouso, Marta, Cueva, Juan, Cabrera, Silvia, Sampayo, Victoria, Arias, Efigenia, Abalo, Alicia, García, Ángel, Lago‐Lestón, Ramón Manuel, Oltra, Sara, Díaz, Eva, Ruiz‐Bañobre, Juan, López‐López, Rafael, Moreno‐Bueno, Gema, Gil‐Moreno, Antonio, Colás, Eva, Abal, Miguel, Muinelo‐Romay, Laura
• Format: Journal Article
• Language: English
• Published: Hoboken, USA John Wiley & Sons, Inc 15-05-2023; Wiley Subscription Services, Inc
• Subjects: Cancer; Cell-Free Nucleic Acids; cfDNA; ctDNA; disease monitoring; Endometrial cancer; Endometrial Neoplasms - genetics; Endometrium; Female; Humans; liquid biopsy; Medical research; Microsatellite Instability; Microsatellite Repeats; Mismatch repair; Paraffin; Polymerase Chain Reaction - methods; Tumors; uterine aspirate; Uterine cancer; microsatellite instability; uterine aspirate; cfDNA; endometrial cancer; disease monitoring; ctDNA; liquid biopsy
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/ijc.34435

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.
What's new?
The analysis of mismatch repair proteins in solid tumor tissue is the current standard of care for microsatellite instability (MSI) characterization in endometrial cancer. Our study demonstrates the accuracy and advantages of MSI analysis by droplet‐digital PCR in uterine aspirates and plasma samples from endometrial cancer patients. The new approach allows comprehensive tumor genotyping without the need for invasive procedures and improves the rate of MSI detection. The assay also has the capacity of monitoring tumor evolution in both localized and metastatic disease by assessing MSI markers. The approach could be easily implemented into the clinic as a follow‐up tool.